Fine-needle aspiration biopsy of the liver: a multicenter study of 602 radiologically guided FNA.

With improved radiologic techniques fine-needle aspiration (FNA) is becoming a rapid, effective diagnostic method in evaluating a wide range of liver masses. Review of six hundred two radiologically guided liver aspirates performed over a ten-year period forms the basis of this report.

The dose-related effects of bolus esmolol on heart rate and blood pressure following laryngoscopy and intubation.

Many researchers have studied esmolol and its effects on heart rate and blood pressure. All studied relatively large doses of esmolol. Therefore, the purpose of the present study was to determine whether small doses of esmolol would blunt the transient increases in blood pressure and heart rate caused by laryngoscopy. This double-blind, prospective, randomized study included 61 subjects. The subjects were randomized to 1 of 3 groups: group 1 received esmolol, 0.2 mg/kg; group 2 received esmolol, 0.4 mg/kg; and group 3 received saline placebo. Groups 1 and 2 had smaller increases in heart rate than group 3. We also found that the 0.4 mg/kg dose significantly blunted the increase in mean arterial pressure seen in group 3. This study shows that small doses of esmolol may block the increases in heart rate and blood pressure resulting from laryngoscopy and intubation.

Identifying DNA and protein patterns with statistically significant alignments of multiple sequences.

MOTIVATION: Molecular biologists frequently can obtain interesting insight by aligning a set of related DNA, RNA or protein sequences. Such alignments can be used to determine either evolutionary or functional relationships. Our interest is in identifying functional relationships. Unless the sequences are very similar, it is necessary to have a specific strategy for measuring-or scoring-the relatedness of the aligned sequences. If the alignment is not known, one can be determined by finding an alignment that optimizes the scoring scheme. RESULTS: We describe four components to our approach for determining alignments of multiple sequences. First, we review a log-likelihood scoring scheme we call information content. Second, we describe two methods for estimating the P value of an individual information content score: (i) a method that combines a technique from large-deviation statistics with numerical calculations; (ii) a method that is exclusively numerical. Third, we describe how we count the number of possible alignments given the overall amount of sequence data. This count is multiplied by the P value to determine the expected frequency of an information content score and, thus, the statistical significance of the corresponding alignment. Statistical significance can be used to compare alignments having differing widths and containing differing numbers of sequences. Fourth, we describe a greedy algorithm for determining alignments of functionally related sequences. Finally, we test the accuracy of our P value calculations, and give an example of using our algorithm to identify binding sites for the Escherichia coli CRP protein. AVAILABILITY: Programs were developed under the UNIX operating system and are available by anonymous ftp from ftp://beagle.colorado.edu/pub/consensus.

PromFD 1.0: a computer program that predicts eukaryotic pol II promoters using strings and IMD matrices.

MOTIVATION: A large number of new DNA sequences with virtually unknown functions are generated as the Human Genome Project progresses. Therefore, it is essential to develop computer algorithms that can predict the functionality of DNA segments according to their primary sequences, including algorithms that can predict promoters. Although several promoter-predicting algorithms are available, they have high false-positive detections and the rate of promoter detection needs to be improved further. RESULTS: In this research, PromFD, a computer program to recognize vertebrate RNA polymerase II promoters, has been developed. Both vertebrate promoters and non-promoter sequences are used in the analysis. The promoters are obtained from the Eukaryotic Promoter Database. Promoters are divided into a training set and a test set. Non-promoter sequences are obtained from the GenBank sequence databank, and are also divided into a training set and a test set. The first step is to search out, among all possible permutations, patterns of strings 5-10 bp long, that are significantly over-represented in the promoter set. The program also searches IMD (Information Matrix Database) matrices that have a significantly higher presence in the promoter set. The results of the searches are stored in the PromFD database, and the program PromFD scores input DNA sequences according to their content of the database entries. PromFD predicts promoters-their locations and the location of potential TATA boxes, if found. The program can detect 71% of promoters in the training set with a false-positive rate of under 1 in every 13,000 bp, and 47% of promoters in the test set with a false-positive rate of under 1 in every 9800 bp. PromFD uses a new approach and its false-positive identification rate is better compared with other available promoter recognition algorithms. The source code for PromFD is in the 'c+2' language.

Comparison of a frequency-based analysis of electroencephalograms (Z-ratio) and visual scoring on the multiple sleep latency test.

In a sample of multiple sleep latency test naps following nocturnal polysomnograms from a group of 13 patients of varying ages and diagnoses, we compared a computer-derived electroencephalographic (EEG) measure (z-ratio) with standard visual sleep stage scoring. In this clinical population, z-ratio scoring agreed with human scorers approximately 80% of the time when determining sleep versus wake in 30-second epochs. These results show that a single, objectively quantifiable value derived from a single channel of EEG can distinguish between sleep and wakefulness (as defined by Rechtschaffen and Kales) with at least a moderate degree of precision. When refined, the z-ratio method might be of use as the basis for a new sleep scoring system, particularly where an accurate determination of sleep onset is required.

MATRIX SEARCH 1.0: a computer program that scans DNA sequences for transcriptional elements using a database of weight matrices.

The information matrix database (IMD), a database of weight matrices of transcription factor binding sites, is developed. MATRIX SEARCH, a program which can find potential transcription factor binding sites in DNA sequences using the IMD database, is also developed and accompanies the IMD database. MATRIX SEARCH adopts a user interface very similar to that of the SIGNAL SCAN program. MATRIX SEARCH allows the user to search an input sequence with the IMD automatically, to visualize the matrix representations of sites for particular factors, and to retrieve journal citations. The source code for MATRIX SEARCH is in the 'C' language, and the program is available for unix platforms.

Developmental trends of sleep-disordered breathing in Prader-Willi syndrome: the role of obesity.

Polysomnographic recordings of 43 children and adults with Prader-Willi syndrome (PWS) were inspected and classified into 5 age groups. The effect of age and body mass index (BMI) on measures of breathing, oxygen saturation, and sleep efficiency were analyzed. Body mass index (BMI) increased significantly between early childhood and preadolescent groups. Subjecting the data to analysis of variance showed an overall significant effect of BMI but no age effect on breathing parameters and oxygen saturation. Increased BMI was associated with decreased oxygen saturation and with higher apnea/hypopnea index. Sleep efficiency index was significantly lower in adults than in young children, preadolescent, and adolescent groups. These findings emphasize the role of obesity in the development of sleep-related breathing abnormalities and nocturnal oxygen desaturation in patients with PWS.

Premature infants in car seats: effect of sleep state on breathing.

Previous studies have shown that premature infants may be at risk for hypoxemia and bradycardia when placed in standard car seats. However, the relationship of such breathing abnormalities to sleep state have not been studied. The purpose of the present study was to investigate the effect of car seat positioning on respiratory patterns in preterm infants during sleep and to evaluate their relationship to sleep state. Complete polysomnography, including sleep and breathing parameters, was performed on twenty-eight premature infants. Each infant was randomly assigned to the car seat or prone (crib) position for the first recording period. Following the recording of at least two sleep cycles, the position was reversed. The percentage of active and quiet sleep was calculated and breathing parameters were measured. In the car seat, the infants spent significantly more time in active sleep and less time in quiet sleep than in the prone position, of the respiratory parameters, periodic breathing (PB) was significantly higher in the car seat. The presence of at least one abnormal breathing events (bradycardia, desaturation, PB apnoea) was also significantly higher in the car seat. An analysis of variance (ANOVA) of PB revealed significant sleep-state effect (active vs. quiet sleep), but no significant condition or interaction effects, indicating that PB was more frequent in active sleep regardless of the sleeping condition. It is concluded that increased active sleep in the car seat condition, rather than the positioning of the infant in the seat per se, may account for the increase in periodic breathing and possibly other breathing abnormalities reported in car seats.

Migration of a ventriculoperitoneal shunt into the pulmonary artery.

Ventriculoperitoneal (VP) shunts have been reported to migrate into a number of unusual locations within the abdomen, chest, and pelvis. We report a case in which a documented, correctly placed VP shunt subsequently migrated to an intravascular location. This intravascular migration led to malposition of the shunt tubing within the pulmonary artery. Attempts to remove the catheter via a postauricular incision were complicated by arrhythmias induced by traction on the shunt tubing. Eventual removal of the shunt was accomplished in stages, through the use of an intravascular, radiographically guided snare, introduced through the femoral vein.

Detection of deletions in the mitochondrial genome of Caenorhabditis elegans.

We have examined an aging population of Caenorhabditis elegans via a PCR assay to determine if deletions in the mitochondrial genome occur in the nematode. We detected eight such deletions, identified the breakpoints of four of these, and discovered direct repeats of 4-8 base pairs at the site of all four deletions. Six of the eight repeats involved in the deletions are located in or immediately adjacent to tRNAs. Without a biochemical bias, the probability of direct repeats being present at all four breakpoints was 4 x 10(-6).

Sleep in the elderly patient.

Sleep problems in the elderly are extraordinarily common. The authors discuss normal sleep, changes in sleep with normal aging, and sleep disorders in the elderly, focusing on sleep-disordered breathing. In addition, nocturnal myoclonus and rapid-eye movement behavior disorder are reviewed.

Sleep and breathing patterns in patients with Prader Willi syndrome (PWS): effects of age and gender.

Patients with Prader Willi syndrome (PWS) often complain of daytime hypersomnolence. Because of reported daytime sleepiness and high prevalence of morbid obesity, these patients have been considered at risk for sleep related disordered breathing, but polysomnographic studies have been limited. We evaluated sleep and breathing polysomnographically in 24 PWS patients including 15 adults and 9 children. All adult patients completed MSLT testing on the day following the nocturnal sleep study. Both adult and children groups showed little or no sleep apnea, but REM related oxygen desaturation was quite common, its severity significantly correlated with increased obesity. Sleep patterns in both groups showed abnormal REM sleep cycles with variable REM latency (at times significantly shortened) and fragmented REM sleep with multiple brief REM periods. REM sleep abnormalities were still present in some patients without REM related desaturation. As a group, patients with PWS demonstrated pathological somnolence as measured by MSLT, which correlated with nocturnal sleep efficiency but not with nocturnal REM latency. It is hypothesized that the abnormal sleep findings in PWS reflect an underlying hypothalamic dysfunction characteristic of this syndrome.

DNA sequences at immunoglobulin switch region recombination sites.

The immunoglobulin heavy chain switch from synthesis of IgM to IgG, IgA or IgE is mediated by a DNA recombination event. Recombination occurs within switch regions, 2-10 kb segments of DNA that lie upstream of heavy chain constant region genes. A compilation of DNA sequences at more than 150 recombination sites within heavy chain switch regions is presented. Switch recombination does not appear to occur by homologous recombination. An extensive search for a recognition motif failed to find such a sequence, implying that switch recombination is not a site-specific event. A model for switch recombination that involves illegitimate priming of one switch region on another, followed by error-prone DNA synthesis, is proposed.

Respiration during sleep in pregnancy.

Several changes in maternal physiology may profoundly alter sleep, especially during late pregnancy. Any condition that causes maternal hypoxemia will be worsened during sleep, particularly in the supine position. Although high circulating levels of progesterone increase respiratory drive during sleep, in at least some women this protective mechanism is insufficient to prevent sleep-disordered breathing and hypoxemia. The true incidence of sleep-disordered breathing during pregnancy remains unknown. Although many women report sleep disturbance during pregnancy, those with severe snoring, observed irregular breathing with sleep, or excessive daytime somnolence should be referred for clinical polysomnography. With few data thus far available, nasal CPAP would appear to be the treatment of choice. Given the possible consequences of sleep apnea for fetal outcome, any significant sleep-disordered breathing is probably an indication for treatment.

Identifying constraints on the higher-order structure of RNA: continued development and application of comparative sequence analysis methods.

Comparative sequence analysis addresses the problem of RNA folding and RNA structural diversity, and is responsible for determining the folding of many RNA molecules, including 5S, 16S, and 23S rRNAs, tRNA, RNAse P RNA, and Group I and II introns. Initially this method was utilized to fold these sequences into their secondary structures. More recently, this method has revealed numerous tertiary correlations, elucidating novel RNA structural motifs, several of which have been experimentally tested and verified, substantiating the general application of this approach. As successful as the comparative methods have been in elucidating higher-order structure, it is clear that additional structure constraints remain to be found. Deciphering such constraints requires more sensitive and rigorous protocols, in addition to RNA sequence datasets that contain additional phylogenetic diversity and an overall increase in the number of sequences. Various RNA databases, including the tRNA and rRNA sequence datasets, continue to grow in number as well as diversity. Described herein is the development of more rigorous comparative analysis protocols. Our initial development and applications on different RNA datasets have been very encouraging. Such analyses on tRNA, 16S and 23S rRNA are substantiating previously proposed associations and are now beginning to reveal additional constraints on these molecules. A subset of these involve several positions that correlate simultaneously with one another, implying units larger than a basepair can be under a phylogenetic constraint.

Nocturnal low back pain in pregnancy: polysomnographic correlates.

Thirteen women in late stages of pregnancy underwent a polysomnographic study. Eight women (61%) complained of mild nocturnal back pain or back discomfort. Five women (39%) did not complain of nocturnal back pain. The two groups did not differ in total bed time, total sleep time, sleep latency, and wake after sleep onset (WASO). A significant decrease in rapid eye movement (REM) sleep and an increase in stage 2 were observed in the pain group. The same group had a statistically significant decrease in the basal O2 saturation level. The pain group also spent a longer time sleeping in the supine position. We hypothesize that a prolonged stay in the supine position leads to obstruction of the vena cava. In the presence of inadequate collateral circulation, increased pressure and venostasis in combination with a decrease in basal oxygen saturation may lead to hypoxemia, compromise the metabolic supply of the neural structures, and result in pain. It appears, therefore, that the vascular system plays an important role in the pathogenesis of pain. The role played by the disturbed sleep architecture in the production of pain remains to be established. It is possible that the changes observed in sleep architecture result from pain rather than contribute to pain production.