Treatment with amniopatch of premature rupture of membranes after first-trimester chorionic villus sampling

OBJECTIVE: To assess the amniopatch procedure when premature rupture of membranes occurs after first-trimester chorionic villus sampling (CVS). STUDY DESIGN: From May 2001 to June 2004, the amniopatch procedure was offered in cases of premature rupture of membranes after CVS when severe oligohydramnios was present (largest vertical pocket < 2 cm) and persistent (more than 1 week). RESULTS: The amniopatch was placed in five pregnancies at 12-18 weeks of gestation, resulting in amniotic fluid restoration in all but one pregnancy. In three pregnancies, fetal demise was observed at 1, 2 and 36 days after the procedure. The last procedure resulted in a healthy newborn. CONCLUSION: Although the amniopatch restored normal amniotic fluid levels in all cases, 4 of the 5 cases resulted in fetal demise.     

Subclinical affective and cognitive fluctuations in Parkinson's disease: a randomized double-blind double-dummy study of Oral vs. Intrajejunal Levodopa

Journal of Neurology - Chronic levodopa treatment in Parkinson’s disease (PD) may promote undesirable motor and non-motor fluctuations. Compared to chronic oral levodopa treatment, continuous...     

Overall survival of relapsed and refractory multiple myeloma patients after adjusting for crossover in the MM‐003 trial for pomalidomide plus low‐dose dexamethasone

In the phase III MM‐003 trial, pomalidomide plus low‐dose dexamethasone (POM+LoDEX) improved overall survival (OS) versus high‐dose dexamethasone (HiDEX) in 455 patients with relapsed and refractory multiple myeloma (RRMM) after treatment with bortezomib and lenalidomide. Here, a two‐stage Weibull method was used to adjust for the crossover of patients in the HiDEX arm to pomalidomide‐based therapy. The adjusted difference in median OS between patients in the POM+LoDEX and HiDEX arms was 7·0 months (12·7 vs. 5·7 months, respectively). These findings provide important evidence for understanding the clinical efficacy of pomalidomide on OS benefits seen in RRMM patients.     

Stress responses in Prochlorococcus MIT9313 vs. SS120 involve differential expression of genes encoding proteases ClpP,FtsH and Lon

Prochlorococcus is a marine cyanobacterium responsible for a significant part of global primary production as well as being one of the most abundant organisms on Earth. Protein turnover is an essential and poorly understood aspect of the cyanobacterial response to environmental stresses. In the present work, cultures of the SS120 and MIT9313 strains were subjected to several conditions, and quantitative real time RT-PCR was used to measure changes in the expression of genes encoding three representative ATP-dependent proteases. We found common responses to conditions such as aging. However, the expression pattern under nutrient starvation was strikingly different in the two strains, probably reflecting the different regulatory backgrounds of the two ecotypes here studied.     

P-selectin upregulation in bleomycin induced lung injury in rats: effect of N-acetyl-L-cysteine

BACKGROUND: A number of adhesion molecules are involved in the process of neutrophil infiltration into the lung. P-selectin is one of these neutrophil-endothelial cell adhesion molecules. A study was undertaken to examine the involvement of P-selectin in the development of bleomycin induced inflammation and the ability of N-acetyl-L-cysteine to reduce the potential expression of this selectin in rats. METHODS: N-acetyl-L-cysteine (3 mmol/kg po) was administered daily for seven days prior to bleomycin administration (2.5 U/kg). The kinetics of P-selectin expression and the effect of N-acetyl-L-cysteine after bleomycin treatment were measured using radiolabelled antibodies. P-selectin localisation was evaluated by immunohistochemistry and neutrophil infiltration was assessed by myeloperoxidase activity. RESULTS: Bleomycin administration resulted in an upregulation of P-selectin at 1 hour, returning to baseline at 3 hours. Myeloperoxidase activity showed a significant increase at 6 hours after bleomycin administration that lasted for 3 days. N-acetyl-L-cysteine treatment completely prevented these increases. CONCLUSION: Upregulation of P-selectin in the lung is associated with neutrophil recruitment in response to bleomycin. The beneficial effect of N-acetyl-L-cysteine on bleomycin induced lung injury may be explained in part by the prevention of neutrophil recruitment in the inflammatory stage of the disease.     

Incomplete inhibition of the Rb tumor suppressor pathway in the context of inactivated p53 is sufficient for pancreatic islet tumorigenesis

Here, we describe the surprising residual capability of the Rb pathway to negatively regulate proliferation and tumorigenesis in a SV40 large T antigen (Tag)-driven mouse model of pancreatic islet carcinogenesis. Heterogeneous Tag expression during all progression stages suggested that a threshold level of the T antigen oncoprotein might be deterministic for beta-cell hyperproliferation and led us to hypothesize that Tag might not be fully inhibiting the tumor suppressor activity of Rb. Moreover, genomic profiling of these tumors by array CGH pointed to regions of loss on chromosomes 6 and 14, where the Rb pathway inhibitor p27 and Rb itself, respectively, reside. Indeed, genetic ablation of the p27(Kip1) or Rb genes accentuated Tag-induced tumorigenesis, with loss of Rb in particular broadly enhancing multiple parameters of tumorigenesis including the frequency and growth rates of premalignant lesions, of nascent solid tumors, and of invasive carcinomas. The data indicate that attenuation rather than complete inactivation of Rb tumor suppressor gene function, in the context of p53 inhibition, is sufficient to initiate tumorigenesis in this model of islet cell cancer, with the demonstrable possibility that subsequent losses of Rb or its regulators can enhance malignant progression. The results may be relevant to human papillomavirus (HPV)-induced cervical neoplasias where E7 oncogene expression levels or activity (in the case of intermediate/low-risk HPV subtypes) incompletely inhibits Rb tumor suppressor functions, as well as to other neoplasias where initiating oncogenic or tumor suppressor events reduce but do not abrogate Rb function.     

Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors

Function-blocking antibodies to VEGF receptors R1 and R2 were used to probe their roles in controlling angiogenesis in a mouse model of pancreatic islet carcinogenesis. Inhibition of VEGFR2 but not VEGFR1 markedly disrupted angiogenic switching, persistent angiogenesis, and initial tumor growth. In late-stage tumors, phenotypic resistance to VEGFR2 blockade emerged, as tumors regrew during treatment after an initial period of growth suppression. This resistance to VEGF blockade involves reactivation of tumor angiogenesis, independent of VEGF and associated with hypoxia-mediated induction of other proangiogenic factors, including members of the FGF family. These other proangiogenic signals are functionally implicated in the revascularization and regrowth of tumors in the evasion phase, as FGF blockade impairs progression in the face of VEGF inhibition.