Surfactant does not improve survival rate in preterm infants with congenital diaphragmatic hernia

Background

Use of exogenous surfactant in congenital diaphragmatic hernia (CDH) patients is routine in many centers. The authors sought to determine the impact of surfactant use in the premature infant with CDH.

Methods

Data on liveborn infants with CDH from participating institutions were collected prospectively. Surfactant use and timing and outcome data were analyzed retrospectively. The authors evaluated the prenatal diagnosis patients as well. The outcome variable was survival to discharge. Odds ratios with confidence intervals were calculated.

Results

Five hundred ten infants less than 37 weeks’ gestation were entered in the CDH registry. Infants with severe anomalies (n = 80) were excluded. Information on surfactant use was available for 424 patients. Infants receiving surfactant (n = 209) had a greater odds of death than infants not receiving surfactant (n = 215, odds ratio, 2.17, 95% CI: 1.5 to 3.2; P < .01). In prenatally diagnosed infants with immediate distress, there was a trend toward worse survival rates among those receiving surfactant at 1 hour (52 patients) versus those that did not (93 patients; odds ratio, 1.93, 95% CI: 0.96 to 3.9; P < .07).

Conclusions

Surfactant, as currently used, is associated with a lower survival rate in preterm infants with CDH. The use of surfactant replacement in premature infants with CDH can be recommended only within the context of a randomized clinical trial.     

Detection of mutations in the cDNA of the proliferation marker Ki-67 protein in four tumor cell lines

The Ki-67 protein has an essential role in cell proliferation. It is present in all dividing cells of normal and tumor tissues, but absent in resting cells. At present, no data are available about any alterations in the gene of this protein that could contribute to its altered structure and function, resulting in tumor development. We therefore searched for mutations in the Ki-67 gene (MKI67). cDNAs from four tumor cell lines derived from carcinoma of the cervix (HeLa), colon (CXF94, SW480), and lung (A549) were prepared. Defined parts of the cDNA were amplified by specific primers, cloned into pCRII-Blunt-TOPO vector, and replicated in Escherichia coli. The sequence of the amplified products were determined by automated fluorescence sequencing. Eight different mutations were characterized in the four cell lines tested. One is a deletion of a single base at position 1496 causing a truncated protein, the second is a A433T exchange is a silent mutation, and the remaining six mutations result in an amino acid change that might alter the conformation of the protein. Our results show that several mutations exist within the Ki-67 protein's cDNA in four tumor cell lines. These mutations might provide a genetic basis for tumor development.     

Correlations between the step activity monitor and the DynaPort ADL-monitor

OBJECTIVE: This study was performed to evaluate correlations between the DynaPort activity of daily living monitor and the step activity monitor. DESIGN: Experimental study with repeated measures. BACKGROUND: Physical activity becomes more important to assess quality of life, e.g. after clinical interventions such as joint replacement surgery. METHODS: Nine subjects wore both devices simultaneously for two days. Limitations and technical problems caused by the devices were assessed by a questionnaire. Correlation coefficients were calculated between parameters derived from both instruments. RESULTS: Only small limitations and problems were reported. Significant correlations were found between the number of steps (step activity monitor) and the percentage of locomotion (DynaPort) (r=0.95), between the number of steps and the physical activity index (DynaPort) (r=0.71) and between the physical activity index and the percentage of locomotion (r=0.76). Wilcoxon-tests between the first and second measurement of each subject did not reveal significant differences but correlation coefficients were poor (r=0.16-0.36). CONCLUSIONS: After one day of simultaneously wearing both devices, the percentage of locomotion can be obtained using only the step activity monitor for additional days. Poor correlations between the first and the second measurements of each subject underline the necessity to record further days to acquire the level of human physical activity.     

Degree of atherosclerosis predicts short-term commitment for smoking cessation therapy

BACKGROUND: Only little is known about factors that influence the smokers' propensity to start smoking cessation therapy and stay within such programs. METHODS: One hundred fifteen subjects that were current smokers and presented at the angiologic outpatient unit were enrolled in a prospective cohort study. All patients were invited to take part in a smoking cessation program. Patients' history, noninvasive vascular, cardiac, and pulmonary parameters, state of atherosclerotic disease (SMART-score), smoking history, and Fagerstr?m index were obtained and the carbon monoxide breathing test was performed. RESULTS: Lower age and heavy smoking were associated with less propensity to start smoking cessation therapy. The degree of atherosclerosis significantly predicted short-term commitment to smoking cessation therapy (relative risk for discontinuation: 0.82; 95% CI: 0.70-0.96). Single factors predictive for staying within the therapy were peripheral arterial occlusive disease and hyperlipidemia, while neither prior myocardial infarction nor pulmonary function was associated with compliance. Fifty-four percent of patients that completed 3 months of therapy quit smoking. CONCLUSIONS: Counseling in smokers with preexistent or newly diagnosed atherosclerotic diseases or risk factors should include their specific vascular condition and information on positive consequences on the progress of these conditions. Counseling for initiation of smoking cessation therapy should apply different strategies as used in the maintenance phase of therapy.     

Influence of polymorphisms in the factor VII gene promoter on activated factor VII levels and on the risk of myocardial infarction in advanced coronary atherosclerosis

In this study, we investigate the influence of three factor VII (FVII) gene polymorphisms on activated FVII levels (FVIIa), and also on the risk of myocardial infarction (MI) in patients with advanced coronary atherosclerotic disease (CAD). The -323A2 allele in the promoter is known to be associated with low FVII levels, and has been suggested to protect against MI in some studies. The -402GA promoter polymorphism, that in vitro has been associated with having opposite effect, is less well studied clinically. For this study, plasma FVIIa levels and three FVII gene polymorphisms were assessed in 934 subjects of both sexes, all with an angiographic documentation of coronary vessels. Our results show that two promoter polymorphisms, plasma cholesterol, and gender, were significant predictors of FVIIa levels. The -402A allele was associated to a significant increase of FVIIa levels in males (by 19.2%). In a selected clinical model including the patients with severe CAD, with or without a thrombotic complication (MI), male carriers of the -402A had an increased risk of MI (OR=1.79; 95% CI 1.15-2.80). The -323A2 allele was associated to a significant decrease in FVIIa (by 36.02% in males, and 39.7% in females). Male carriers of the -323A2 were protected from MI (OR=0.6; 95% CI 0.39-0.94), but only after correction for the confounding effect of combined heterozygosity for the promoter polymorphisms. We can conclude that FVII gene polymorphisms with an opposite effect on FVIIa levels may modulate the risk of MI in males with advanced CAD. This study highlights a "within-gene" interaction, and the need to explore polymorphisms in candidate gene(s) in detail.     

Tau protein phosphorylated at threonine 181 in CSF as a neurochemical biomarker in Alzheimer’s disease

Cerebrospinal fluid (CSF) concentrations of total Tau and Tau phosphorylated at threonine (position 181 [pTau181]) were studied with ELISA in a group of carefully selected patients with a neurochemically supported diagnosis of Alzheimer's disease (AD, n = 9; age range, 51-89 yr) and in a group of sex- and age-matched nondemented controls (n = 9; age range, 52-81 yr). The concentration of both biomarkers is increased significantly in the AD group (total Tau, p < 0.0008; pTau181, p < 0.008). A significant correlation between CSF concentrations of both biomarkers is observed (R = 0.897; p < 0.001). Neither total Tau nor pTau181 correlates with age or degree of memory impairment, and only a tendency is observed between the concentrations of total Tau and Abeta42 in the CSF. Our results further confirm a possible role of pTau181 as a diagnostic tool in AD. The current literature regarding the physiological and pathological role of phosphorylated Tau proteins is reviewed, as well as the role of these proteins as promising biomarkers in the diagnosis of neurodegenerative disorders.     

Contrast-enhanced US of hepatocellular carcinoma

PURPOSE: To evaluate the capabilities of contrast-enhanced ultrasound (CEUS) in the characterization of hepatocarcinoma (HCC) in terms of accuracy as compared to spiral CT and diagnostic gain as compared to conventional and Doppler US. MATERIALS AND METHODS: Forty-three patients with viral hepatopathy or cirrhosis diagnosed with HCC (6 histologically and 37 cytologically proven) were retrospectively studied. Between January 2002 and May 2003, all patients were evaluated with CEUS after detection of at least one suspicious nodule on US. CEUS features of HCCs were retrospectively compared with those on conventional and Doppler US, and spiral CT. RESULTS: HCCs varied between 1.2 cm and 18 cm in diameter; 14/43 were small' (< or = 2 cm). In 18/43 patients, HCC was multifocal. Doppler US revealed 24/43 hypervascular nodules. On CEUS, 37/43 (86%) showed contrast enhancement in the arterial phase, 13/37 (35%) with negative colour and power Doppler US examination; in 6/37 (16%) contrast enhancement in the arterial phase was not visible on spiral CT. On CEUS, 6/43 hypovascular HCCs were characterized as malignant in the sinusoidal phase. On CEUS, the sinusoidal phase revealed additional nodules not visible on baseline US in 3/18 multifocal HCCs. CONCLUSIONS: CEUS diagnosis of HCC in cirrhotic liver is possible with a combination of the arterial phase, which shows tumoral hypervascularity in the microcirculation, and the sinusoidal phase, which allows to confirm the malignancy of the nodule.     

3H-noradrenaline release from mouse iris–ciliary body: role of presynaptic muscarinic heteroreceptors

Sympathetic neurotransmitter release and its modulation by presynaptic muscarinic heteroreceptors were studied in mouse iris–ciliary bodies. Tissue preparations were preincubated with ³H-noradrenaline and then superfused and stimulated electrically. Firstly, experimental conditions were defined, allowing study of presynaptic sympathetic inhibition in mouse iris–ciliary body. If tissue was stimulated four times with 36 pulses/3 Hz, tritium overflow peaks were reliably and reproducibly measured. As expected, these stimulation conditions led to marked ₂-autoinhibition as indicated by the release-enhancing effect of the ₂-antagonists phentolamine and rauwolscine. To ensure autoinhibition-free ³H-noradrenaline release, which is optimal for studying presynaptic sympathetic inhibition, ₂-receptors were blocked in all subsequent experiments. Under these conditions, evoked tritium overflow was almost completely abolished in the presence of the sodium channel blocker tetrodotoxin, indicating a neuronal origin of ³H-noradrenaline release. Secondly, muscarinic inhibition of ³H-noradrenaline release was characterized using the conditions described above (36 pulses/3 Hz; phentolamine 1 M and rauwolscine 1 M throughout). The muscarinic receptor agonist oxotremorine M decreased evoked tritium overflow in a concentration-dependent manner with an IC₅₀ of 0.33 M and maximal inhibition of 51%. The concentration–response curve of oxotremorine M was shifted to the right by the muscarinic antagonists ipratropium and methoctramine, whereas pirenzepine was ineffective. The observed rank order of antagonist potencies, ipratropium > methoctramine > pirenzepine, which is typical for the M₂ subtype, indicates that presynaptic muscarinic receptors on sympathetic axons of mouse iris–ciliary bodies are predominantly M₂. Finally, inhibition of ³H-noradrenaline release by endogenously secreted acetylcholine was investigated. Longer pulse trains, 120 pulses/3 Hz and 600 pulses/5 Hz, were used and the cholinesterase inhibitor physostigmine was added to the superfusion medium to increase synaptic levels of endogenous acetylcholine. Under these conditions, ipratropium approximately doubled the evoked overflow of tritium, indicating that endogenously released acetylcholine can activate presynaptic muscarinic heteroreceptors. In conclusion, the present experiments establish measurement of the electrically induced release of ³H-noradrenaline from mouse iris–ciliary bodies. As in other species, noradrenaline release in this preparation was subject to presynaptic muscarinic inhibition. Our results also indicate that the presynaptic muscarinic receptors on sympathetic axons in mouse iris–ciliary body are predominantly M₂. Moreover, these receptors can be activated by both exogenous agonists and endogenously released acetylcholine and, hence, may operate physiologically in the interplay between the parasympathetic and sympathetic nervous system.