Attenuated lipid peroxidation in preterm infants during subsequent doses of intravenous lipids

The aim of this study was to determine whether the administration of a lipid emulsion containing less polyunsaturated fatty acids but rich in monounsaturated fatty acids causes less in vivo lipid peroxidation in preterm infants. The prospective intervention study included 13 infants with birth weights and gestational ages ranging between 1,100 and 2,660 g and from 28.4 to 32.9 weeks. All were in a stable condition and randomly allocated for a 3-hour infusion (0.16 g/kg/h) of an olive oil-based and a soybean oil + medium chain fatty acid (MCT) emulsion on 2 consecutive days. Expired pentane and plasma triglycerides (TGs) were measured before, during, and after the 3-hour infusion. Basal exhaled pentane averaged 9.4 +/- 7.0 pmol/kg/min (mean +/- SD). During the olive oil-based emulsion, exhaled pentane increased to 95.2 +/- 56.7, and during soybean oil + MCT it increased to 110 +/- 93.9 pmol/kg/min (p < 0.05 both from basal, n.s. between preparations). One hour after discontinuation of the infusion, exhaled pentane returned to 21.1 +/- 12.6 pmol/kg/min (p < 0.05 vs. basal). Combined data on expired pentane measurements demonstrated that on day 1 pentane peaked at 124 +/- 87.0 pmol/kg/min which was significantly attenuated to 57.5 +/- 24.4 pmol/kg/min after an identical dose of lipid on day 2 (p < 0.05). No difference in peak TGs was detected between the two preparations or the study days. Infusion of a constant dose of intravenous lipids on 2 subsequent days to the newborn infants is associated with a reduction in lipid peroxidation. This finding may be dependent on normal postnatal maturation or may represent an appropriate adaptive response aiming at a reduction in oxidative stress. Peroxidation of soybean oil + MCT and olive oil-based lipid emulsions was similar in the newborn infants.     

Long-term outcome after intravenous thrombolysis of basilar artery occlusion

Context  Basilar artery occlusion (BAO) is an infrequent disease with high morbidity and mortality. Intra-arterial thrombolysis is advocated for treatment but is limited to use at specialized centers. Objective  To evaluate outcomes for patients with BAO treated with intravenous thrombolytic therapy. Design, Setting, and Participants  During 1995 to 2003, 50 consecutive patients with angiographically proven BAO were treated according to an institutional therapy protocol based on intravenous thrombolysis with recombinant tissue plasminogen activator (alteplase). Patients were treated at an urban university teaching hospital receiving all patients with ischemic stroke who were considered for thrombolysis in a catchment area of 1.5 million inhabitants in Helsinki, Finland. Intervention  Intravenous administration of alteplase (0.9 mg/kg) during a 1-hour infusion. Main Outcome Measures  Basilar artery recanalization determined by magnetic resonance angiography and clinical outcomes at 3 months and at 1 year or longer determined by modified Rankin Scale and Barthel Index scores. Results  Recanalization was studied in 43 patients and verified in 26 (52%) of all patients. By 3 months, 20 patients (40%) had died while 11 had good outcomes (modified Rankin Scale score, 0-2); 12 (24%) reached independence in activities of daily living (Barthel Index score, 95-100), and 6 (16%) were severely disabled (Barthel Index score, 0-50). In the long term (median follow-up 2.8 years), 15 patients (30%) reached good outcomes (modified Rankin Scale score, 0-2) while 23 (46%) died. Conclusions  Intravenous administration of alteplase for patients with BAO appears to be associated with rates of survival, recanalization, and independent functional outcome comparable with those reported with endovascular approaches. These data suggest that a randomized trial is needed to compare these approaches for treatment of BAO.      

CHEK2 1100delC is not a risk factor for male breast cancer population

Genetic risk factors for male breast cancer (MBC) are poorly understood. High penetrance genes such as BRCA1 or BRCA2 account for only a small proportion of the disease. A 1100delC mutation in CHEK2 (previously known as CHK2), a cell-cycle checkpoint kinase, has been implicated in predisposition of Li-Fraumeni syndrome (LFS) and breast cancer in families suggestive of LFS. This 1100delC mutation has also been shown to confer a 2-fold increase of breast cancer risk in women and a 10-fold increase of risk in men. It was estimated to account for 1% of breast cancers in women and as much as 9% of breast cancers in men at the population level based on analysis of breast cancer families without BRCA1 or BRCA2 mutations. We wanted to evaluate the significance of CHEK2 1100delC in predisposition to MBC by assessing its frequency in a population-based material of 114 Finnish MBC patients. Two patients (1.8%) carried the 1100delC mutation. The mutation frequency among MBC cases was similar to that seen in population controls (26/1885, 1.4%). Our results indicate that CHEK2 1100delC variant does not substantially increase the risk of male breast cancer at the population level. We cannot exclude the fact that a small fraction of hereditary, family-positive male breast cancers could be attributable to CHEK2 mutations.     

Long-term progestin therapy for female chronic respiratory insufficiency?

End-stage chronic obstructive pulmonary disease often leads to hypercapnic respiratory failure. Oxygen supplementation therapy may further aggravate hypercapnia and not all patients are compliant with non-invasive ventilation. This case documents successful control of chronic respiratory failure with medroxyprogesterone in a postmenopausal woman during 1-year follow-up.     

Progression of brain damage after status epilepticus and its association with epileptogenesis: a quantitative MRI study in a rat model of temporal lobe epilepsy

PURPOSE: This study examined the hypothesis that neurodegeneration continues after status epilepticus (SE) ends and that the severity of damage at the early phase of the epileptogenic process predicts the outcome of epilepsy in a long-term follow-up. METHODS: SE was induced in rats by electrical stimulation of the amygdala, and the progression of structural alterations was monitored with multiparametric magnetic resonance imaging (MRI). Absolute T2, T1rho, and diffusion (Dav) images were acquired from amygdala, piriform cortex, thalamus, and hippocampus for < or = 4.5 months after SE. Frequency and type of spontaneous seizures were monitored with video-electroencephalography recordings. Histologic damage was assessed from Nissl, Timm, and Fluoro-Jade B preparations at 8 months. RESULTS: At the acute phase (2 days after SE induction), quantitative MRI revealed increased T2, T1rho, and Dav values in the primary focal area (amygdala), reflecting disturbed water homeostasis and possible early structural damage. Pathologic T2 and T1rho were observed in mono- or polysynaptically connected regions, including the piriform cortex, midline thalamus, and hippocampus. The majority of acute MRI abnormalities were reversed by 9 days after SE. In later time points (> 20 days after induction), both the T1rho and diffusion MRI revealed secondarily affected areas, most predominantly in the amygdala and hippocampus. At this time, animals began to have spontaneous seizures. The initial pathology revealed by MRI had a low predictive value for the subsequent severity of epilepsy and tissue damage. CONCLUSIONS: The results demonstrate progressive neurodegeneration after SE in the amygdala and the hippocampus and stress the need for continued administration of neuroprotectants in the treatment of SE even after electrographic seizure activity has ceased.     

High-resolution genomic and expression profiling reveals 105 putative amplification target genes in pancreatic cancer

Comparative genomic hybridization (CGH) studies have provided a wealth of information on common copy number aberrations in pancreatic cancer, but the genes affected by these aberrations are largely unknown. To identify putative amplification target genes in pancreatic cancer, we performed a parallel copy number and expression survey in 13 pancreatic cancer cell lines using a 12,232-clone cDNA microarray, providing an average resolution of 300 kb throughout the human genome. CGH on cDNA microarray allowed highly accurate mapping of copy number increases and resulted in identification of 24 independent amplicons, ranging in size from 130 kb to 11 Mb. Statistical evaluation of gene copy number and expression data across all 13 cell lines revealed a set of 105 genes whose elevated expression levels were directly attributable to increased copy number. These included genes previously reported to be amplified in cancer as well as several novel targets for copy number alterations, such as p21-activated kinase 4 (PAK4), which was previously shown to be involved in cell migration, cell adhesion, and anchorage-independent growth. In conclusion, our results implicate a set of 105 genes that is likely to be actively involved in the development and progression of pancreatic cancer.