[Uveal and iridociliary melanomas in young patients : A retrospective analysis of 57 cases]. / Aderhaut- und Ziliarkörpermelanome bei jungen Patienten : Eine retrospektive Analyse von 57 Fällen.

BACKGROUND: Uveal melanomas (UM) are rare malignancies in young patients. It is unknown if UM in young patients significantly differs from those in older patients concerning tumor size and localization, metastasis and genetics. The aim of this study was to evaluate the clinical course and tumor characteristics in young patients with UM. MATERIAL AND METHODS: All patients with UM below the age of 32 years who had been treated at our hospital were included in the study. Patient age and sex, duration of symptoms, visual impairment, tumor size and location, genetics, therapy, follow-up interventions and tumor-associated deaths were documented. RESULTS: A total of 57 patients (67 % male, mean age 24.7 years) were included in the study with an average symptomatic course of 5 months. Of the patients 8 (14 %) had an initial visual acuity of ≥ 0.9, 16 (28 %) 0.5-0.8, 22 (39 %) 0.05-0.4 and 9 (16 %) < 0.05 (no data for 2 patients, 4 %). After therapy visual acuity was < 0.05 in 54 % and 53 % of the tumors were choroidal UM (70 % juxtapapillary/circumpapillary), whereas 47 % were ciliochoroidal (54 % with iridociliary involvement). The average tumor size was 12.7 ± 3.6 mm with an average prominence of 6.2 ± 3.2 mm. Genetic evaluation (n = 16) revealed disomy 3 in 64 % and 54 % of the patients received radiotherapy with local application of ruthenium 106. In 46 % of cases follow-up interventions were neccessary including 70 % due to radiogenic retinopathy. CONCLUSION: In young patients UM did not show any preferred localization. The majority of genetically evaluated tumors revealed disomy 3 with no significant correlation to tumor location. Independent of tumor size, location and therapy, approximately half of the patients needed follow-up interventions, predominantly due to radiogenic retinopathy.

Tapering for marathon and cardiac autonomic function.

The purpose of this study was to investigate changes in post-exercise heart rate recovery (HRR) and heart rate variability (HRV) during an overload-tapering paradigm in marathon runners and examine their relationship with running performance. 9 male runners followed a training program composed of 3 weeks of overload followed by 3 weeks of tapering (-33 ± 7%). Before and after overload and during tapering they performed an exhaustive running test (T(lim)). At the end of this test, HRR variables (e.g. HRR during the first 60 s; HRR(60 s)) and vagal-related HRV indices (e.g. RMSSD(5-10 min)) were examined. T(lim) did not change during the overload training phase (603 ± 105 vs. 614 ± 132 s; P = 0.992), but increased (727 ± 185 s; P = 0.035) during the second week of tapering. Compared with overload, RMSSD(5-10 min) (7.6 ± 3.3 vs. 8.6 ± 2.9 ms; P = 0.045) was reduced after the 2(nd) week of tapering. During tapering, the improvements in T(lim) were negatively correlated with the change in HRR(60 s) (r = -0.84; P = 0.005) but not RMSSD(5-10 min) (r = -0.21; P = 0.59). A slower HRR during marathon tapering may be indicative of improved performance. In contrast, the monitoring of changes in HRV as measured in the present study (i.e. after exercise on a single day), may have little or no additive value.

MAGIC Tool: integrated microarray data analysis.

SUMMARY: Several programs are now available for analyzing the large datasets arising from cDNA microarray experiments. Most programs are expensive commercial packages or require expensive third party software. Some are freely available to academic researchers, but are limited to one operating system. MicroArray Genome Imaging and Clustering Tool (MAGIC Tool) is an open source program that works on all major platforms, and takes users 'from tiff to gif'. Several unique features of MAGIC Tool are particularly useful for research and teaching. AVAILABILITY: http://www.bio.davidson.edu/MAGIC

Exploring expression data: identification and analysis of coexpressed genes.

Analysis procedures are needed to extract useful information from the large amount of gene expression data that is becoming available. This work describes a set of analytical tools and their application to yeast cell cycle data. The components of our approach are (1) a similarity measure that reduces the number of false positives, (2) a new clustering algorithm designed specifically for grouping gene expression patterns, and (3) an interactive graphical cluster analysis tool that allows user feedback and validation. We use the clusters generated by our algorithm to summarize genome-wide expression and to initiate supervised clustering of genes into biologically meaningful groups.

Effects of prone position on alveolar recruitment and oxygenation in acute lung injury.

OBJECTIVE: To investigate the effects of prone position (PP) on alveolar recruitment and oxygenation in acute respiratory failure. DESIGN: Prospective physiologic study. SETTING: Medical ICU two in a university hospital. PATIENTS: Twelve adult patients intubated and mechanically ventilated with medical primary acute lung injury/adult respiratory distress syndrome (ALI/ARDS) in whom PP was indicated. MEASUREMENTS AND RESULTS: We constructed the static inflation volume-pressure curves (V-P) of the respiratory system in the 12 patients and differentiated between lung and chest wall in ten of them. We determined the difference between end-expiratory lung volume on positive end-expiratory pressure (PEEP) and relaxation volume of the respiratory system on zero PEEP (delta FRC). The recruited alveolar volume was computed as the delta FRC times the ratio of static elastance of the respiratory system to the lung. These measurements together with arterial blood gases determination were made in supine position (SP1), after 1 h of PP and after 1 h of supine repositioning (SP2) at the same level of PEEP. The PaO2/FIO2 ratio improved from SP1 to PP (136 +/- 17 vs 204 +/- 24 mm Hg; p < 0.01). An PP-induced alveolar recruitment was found in five patients. The change in oxygenation correlated to the recruited volume. The static elastance of the chest wall decreased from 4.62 +/- 0.99 cmH2O/l in SP1 to 6.26 +/- 0.54 cmH2O/l in PP (p < 0.05) without any correlation to the change in oxygenation. CONCLUSIONS: Alveolar recruitment may be a mechanism of oxygenation improvement in some patients with acute hypoxemic respiratory failure. No correlation was found between change in oxygenation and chest wall elastic properties.

[The value of the CT scanner in intensive care]. / Apport de la TDM en réanimation respiratoire.

Chest x-rays are often the first examination carried out at the bed side on patients in intensive care and their interpretation is often difficult. When CT scans are carried out they enable the mediastinum to be examined as well as the bronchi and pulmonary parenchyma. Using this technique to confirm a diagnosis or to explain those aspects on a standard x-ray which were difficult to analyse increasingly justifies the transportation of a patient the scanner. Spiral CT scans are particularly useful in the diagnosis of pulmonary emboli.

Finding the most significant common sequence and structure motifs in a set of RNA sequences.

We present a computational scheme to locally align a collection of RNA sequences using sequence and structure constraints. In addition, the method searches for the resulting alignments with the most significant common motifs, among all possible collections. The first part utilizes a simplified version of the Sankoff algorithm for simultaneous folding and alignment of RNA sequences, but maintains tractability by constructing multi-sequence alignments from pairwise comparisons. The algorithm finds the multiple alignments using a greedy approach and has similarities to both CLUSTAL and CONSENSUS, but the core algorithm assures that the pairwise alignments are optimized for both sequence and structure conservation. The choice of scoring system and the method of progressively constructing the final solution are important considerations that are discussed. Example solutions, and comparisons with other approaches, are provided. The solutions include finding consensus structures identical to published ones.

Carbon dioxide respiratory response during positive inspiratory pressure in COPD patients.

The aim of this study was to compare the effect of inspiratory pressure support (IPS) on the respiratory CO2 response in 13 stable COPD patients and in 13 normal subjects. Without IPS, the slopes of the ventilatory response to CO2 were lower in the patients than in the normal subjects (mean +/- SEM, 0.82 +/- 0.19 vs. 1.69 +/- 0.31 l.min-1.mmHg-1). When IPS was applied, both groups showed, at any level of end-tidal CO2 pressure, an increase in ventilation due to an increase in tidal volume (VT) associated with a decrease in occlusion pressure (P0.1). In addition, respiratory parameters (VE, VT, P0.1, inspiratory flow) were insensitive to CO2 as long as PETCO2 remained below a threshold which was slightly above the eupneic value. However, above this CO2-threshold, no differences in slopes were observed between the IPS and control conditions in either group, except for a decrease in the P0.1 slope during IPS in the COPD patients. In conclusion, IPS induced similar respiratory changes during CO2 response in stable COPD patients and in normal subjects. Above the eupneic value, IPS did not change the slope of the ventilatory response to CO2.

Sleep apnea-like syndrome induced by nitrous oxide inhalation in normal men.

To study the relationship between sedation and respiration under N2O, we performed polysomnographic recordings in 15 healthy men with documented normal breathing patterns during sleep. In a first study in five subjects, we found that 50% N2O in O2 compared to 50% O2 increased sleep latency to stage 2 (59 +/- 12 vs. 17 +/- 3 min), total sleep duration (59 +/- 12 vs. 26 +/- 11 min), depth of sleep and respiratory events during sleep (18 +/- 5 vs. 1 +/- 1/h of sleep). In a second study, ten subjects were exposed to N2O (30 and 50%) in O2 during two consecutive experimental periods. Eight subjects had EEG features of physiological sleep, but nevertheless exhibited a total of 181 respiratory events. Respiratory disturbance index (RDI) during sleep was similar under 30 and 50% N2O (25 +/- 7 and 25 +/- 5/h of sleep, respectively). Obstructive events predominated, except in three subjects during N2O 30% and one during N2O 50% exposure. We conclude that N2O can induce central and obstructive sleep apneas.

Finding common sequence and structure motifs in a set of RNA sequences.

We present a computational scheme to search for the most common motif, composed of a combination of sequence and structure constraints, among a collection of RNA sequences. The method uses a simplified version of the Sankoff algorithm for simultaneous folding and alignment of RNA sequences, but maintains tractability by constructing multi-sequence alignments from pairwise comparisons. The overall method has similarities to both CLUSTAL and CONSENSUS, but the core algorithm assures that the pairwise alignments are optimized for both sequence and structure conservation. Example solutions, and comparisons with other approaches, are provided. The solutions include finding consensus structures identical to published ones.

Displaying the information contents of structural RNA alignments: the structure logos.

MOTIVATION: We extend the standard 'Sequence Logo' method of Schneider and Stevens (Nucleic Acids Res., 18, 6097-6100, 1990) to incorporate prior frequencies on the bases, allow for gaps in the alignments, and indicate the mutual information of base-paired regions in RNA. RESULTS: Given an alignment of RNA sequences with the base pairings indicated, the program will calculate the information at each position, including the mutual information of the base pairs, and display the results in a 'Structure Logo'. Alignments without base pairing can also be displayed in a 'Sequence Logo', but still allowing gaps and incorporating prior frequencies if desired. AVAILABILITY: The code is available from, and an Internet server can be used to run the program at, http://www.cbs.dtu.dk/gorodkin/appl/slogo. html.

Noninvasive estimate of work of breathing due to the endotracheal tube.

BACKGROUND: Although evidence suggests that secretions lining the inner wall of the endotracheal tube (ETT) often reduce its cross-sectional area, no data are available on the work of breathing as affected by the ETT. A noninvasive method is proposed for estimating the additional work of breathing necessitated by the ETT in patients whose lungs are mechanically ventilated. This method (the acoustic-Blasius method) involves (1) determining the inner geometry of the ETT using the acoustic reflection method and (2) using these geometric data to solve the Blasius equation that characterizes the ETT pressure drop-flow relation. METHODS: To evaluate the acoustic-Blasius method in vivo, the authors computed the work of breathing due to the ETT in four healthy persons breathing through an ETT connected to a pressure-support device and in five tracheally intubated patients receiving mechanical assistance in the pressure-support mode. For the tracheally intubated patients, the reference value was the work calculated from the ETT pressure drop measured between the two ends of the ETT using a pressure catheter. RESULTS: In the healthy participants and the tracheally intubated patients, there was close agreement between inspiratory work per cycle values estimated by directly measuring the ETT pressure drop and calculated using the acoustic-Blasius method: The difference was consistently less than 0.08 joules (< 10% of the reference value). CONCLUSIONS: The data show that the acoustic-Blasius method allows noninvasive quantification of the ETT-related work of breathing in situ.

Assessment of potential health risks associated with ingesting heavy metals in fish collected from a hazardous-waste contaminated wetland in Louisiana, USA.

Significant adverse effects on environmental quality, ecosystem integrity, and human health have often been associated with improper disposal of hazardous materials. This study ascertains the levels of eight heavy metals in various fish species that were collected from a local hazardous-waste-contaminated wet-land and estimates the potential health risk that may be associated with consuming such fish. We examined a total of 53 fish samples representing 12 different species. The respective mean concentrations (ng/g) of arsenic, cadmium, chromium, copper, iron, lead, mercury, and nickel found in edible tissues were as follows: 72.5 +/- 103.1, 55.4 +/- 34.6, 97.4 +/- 111.7, 177.3 +/- 328.3, 2711.0 +/- 4469.6, 26.0 +/- 119.0, 32.7 +/- 75.3, and 81.5 +/- 178.9. For a 10-kg child eating 6.5 g of fish per day, the computed combined hazard index was 0.475 ; for 70-kg adults with a daily consumption of 6.5 g (general population), 30 g (sport fishermen), and 140 g (subsistence fishermen), the respective computed hazard indices were 0.068, 0.313, and 1.462. The results indicate that subsistence fishermen had the highest risk for systemic effects, with an exposure exceeding the Environmental Protection Agency (EPA) Reference Dose value. In a 10-kg child, such excess exposure would be reached--even with such single metals as arsenic and mercury--when applying the EPA-approved maximum fish consumption rate of 54 g/day to the general population. The cancer risk for arsenic, the only metal with an established cancer potency factor from oral exposure, varied from 8 x 10(-6) to 253 x 10(-6), indicating an exposure exceeding the widely accepted risk level of 1 x 10(-6) (one excess cancer per 10(6) population).

Do turbines with servo-controlled speed improve continuous positive airway pressure generation?

Nasal continuous positive airway pressure (CPAP) devices with a servo-mechanism to control pressure have recently been developed. We evaluated six such devices and three conventional systems in terms of effectiveness in maintaining constant pressure. Machines were tested with pressure levels of 5, 10 and 15 cmH2O. Dynamic behaviour was evaluated: 1) by calculating the imposed work of breathing during simulated breath generated by a sinusoidal pump; and 2) by following the fall in pressure after a transient flow of 1 l.s-1. Quasi-static behaviour was evaluated by simulating a predetermined air leak. Under dynamic conditions, work of breathing was lowest with one conventional nasal CPAP device and three servo-controlled nasal CPAP devices; whereas, the highest levels of work of breathing were recorded with two servo-controlled nasal CPAP devices. The pressure-time response to a transient flow yielded similar results, with a significant inverse correlation between pressure values observed after 300 ms and imposed work of breathing during simulated breathing (r = -0.91). Under quasi-static conditions, microprocessor servo-controlled devices exhibited the best performance. These results suggest that microprocessor servo-controlled nasal CPAP devices are not always the best systems for maintaining constant airway pressure in dynamic situations. However, they are more effective in ensuring maintenance of the desired pressure in the event of an air leak at the mask.