Total simultaneous repair of coarctation and intracardiac pathology in adult patients

OBJECTIVE: To determine whether neutralizing antibodies (NABs) to interferon beta (IFNbeta)-1a (Avonex) and IFNbeta-1b (Betaseron) cross-react. BACKGROUND: A total of 38% of MS patients treated with IFNbeta-1b and 22% of those treated with IFNbeta-1a were reported to develop NABs, which could reduce the clinical efficacy of the drug. METHODS: Blood from 10 MS patients was collected before and at 3 and 6 months after initiating treatment with IFNbeta-1a. ELISA was performed to detect binding antibodies to IFNbeta-1a. Sera from patients who tested positive for binding antibodies to IFNbeta-1a were then screened for NABs to IFNbeta-1a in a biologic assay based on neutralization of antiviral activity. These serum samples were subsequently tested for cross-reactivity with IFNbeta-1b both in the ELISA and the biologic assay. In the second part of the study, sera from patients who participated in the phase III IFNbeta-1b trial at the University of Maryland were examined for cross-reactivity with IFNbeta-1a in the ELISA and the biologic assay. RESULTS: Of the 10 patients treated with IFNbeta-1a, three developed binding as well as NABs to IFNbeta-1a 6 months after treatment, and these antibodies cross-reacted with IFNbeta-1b both in the binding and the biologic assay. Similarly, sera from six patients with NABs to IFNbeta-1b showed cross-reactivity with IFNbeta-1a in the binding assay. Three of these six serum samples tested for neutralizing activity against IFNbeta-1a demonstrated the presence of NABs to IFNbeta-1a. CONCLUSIONS: NABs to IFNbeta-1a (Avonex) and IFNbeta-1b (Betaseron) cross-react, both in the binding and the biologic assays. This suggests that switching to alternate IFNbeta preparation in patients who develop NABs may not be clinically beneficial. Studies examining cross-reactivity between NABs to IFNbeta-1a and IFNbeta-1b in a large number of patients are indicated.     

Telecentric optics for focus analysis

Magnification variations due to changes in focus setting pose problems for vision techniques, such as, depth from focus and defocus. The magnification of a conventional lens can be made invariant to defocus by simply adding an aperture at an analytically derived location. The resulting optical configuration is called “telecentric”. It is shown that most commercially available lenses can be turned into telecentric ones. The procedure for calculating the position of the additional aperture and a detailed analysis of the photometric and geometric properties of telecentric lenses are presented. Experiments are reported that use a phase-based shift detection algorithm to demonstrate the magnification invariance of telecentric lenses     

Mortality studies of machining fluid exposure in the automobile industry. V: A case-control study of pancreatic cancer

MANOVA and repeated measures ANOVA approaches have provided evidence of a number of limitations in several event-related potential (ERP) studies due to violations of their statistical assumptions and the typically moderate size of the available sample. Alternative, computer-intensive methods based on permutation principles have recently been developed. Up to now this methodology has focused mostly on magnitude differences between scalp distributions as measured by t statistics. In this paper the scope of permutation techniques in ERP analysis was widened. A new statistic (D statistic) is introduced to compare the shapes of scalp distributions of ERPs. Additionally a general non-parametric combinatory technique is introduced to evaluate, by means of multivariate permutation tests, several time points and/or recording sites in ERP data. The methodology described here was used to test if two ERP components elicited during word-pair matching tasks to semantic or phonological incongruences had different scalp distributions.     

Safety, functionality and acceptability of a prototype polyurethane condom

The distribution of serotonin immunoreactive elements in the peripheral nervous system of three earthworm species (Lumbricus terrestris, Eisenia fetida and Tubifex tubifex) was studied using the peroxidase-antiperoxidase method. Most parts of the peripheral nervous system contain immunoreactive fibers. All segmental nerves as well as branches of the prostomial nerves show strong immunoreactivity. Muscles of the body wall contain serotonergic fibers, mostly between the circular and longitudinal layers. The best supplied area is the buccal musculature. All parts of the enteric nervous system contain serotonergic fibers, strongest staining was observed in the buccal and pharyngeal walls. Along the wall of the calciferous glands thin immunoreactive fibers were found. The excretory system, the metanephridial tubules also display immunoreactivity. Under the surface epithelium, a serotonergic subepidermal plexus was observed. No significant differences were observed between the species studied. On the basis of our morphological findings and functional studies performed by other authors it is suggested that serotonin plays an essential role in the function of the peripheral nervous system in Oligochaeta.     

Inhibition of potassium (KATP) channels reduces the short-circuit current response of rat colonic mucosa to acetylcholine

Intestinal secretion depends upon electrogenic chloride transport into the gut lumen, which requires maintenance of an electrically negative cell-membrane voltage. We have investigated whether secretory responses of rat colonic mucosa to acetylcholine were sensitive to inhibition of potassium channels and whether selective inhibition could indicate the nature of the channel involved. Rat colonic mucosa was set up in Ussing chambers, short-circuit current responses obtained to acetylcholine, and the sensitivity of such responses to inhibition of potassium channels was investigated. Non-selective potassium-channel blockade by barium induced concentration-dependent inhibition of responses to acetylcholine. Similar inhibitory effects were obtained using 4-aminopyridine and glibenclamide. 5-Hydroxydecanoate and phentolamine also inhibited the increase in short-circuit current. However, a combination of charybdotoxin plus apamin was without effect. We conclude that a basolateral outward movement of potassium ions is required for the secretory action of acetylcholine on rat colonic mucosa. The potassium channel involved seems to be ATP-dependent and calcium-insensitive.     

Orally active inhibitors of human leukocyte elastase. II. Disposition of L-694,458 in rats and rhesus monkeys

The disposition of L-694,458, a potent monocyclic beta-lactam inhibitor of human leukocyte elastase, was studied in male Sprague-Dawley rats and rhesus monkeys. After iv dosing, L-694,458 exhibited similar pharmacokinetic parameters in rats and rhesus monkeys. The mean values for its plasma clearance, terminal half-life, and volume of distribution at steady state were 27 ml/min/kg, 1.8 hr, and 4.0 liters/kg in rats and 34 ml/min/kg, 2.3 hr, and 5 liters/kg in rhesus monkeys. The bioavailability of a 10 mg/kg oral dose was higher in rats (65%) than in rhesus monkeys (39%). In both species, concentrations of L-694,458 in plasma increased more than proportionally when the oral dose was increased from 10 mg/kg to 40 mg/kg. In monkeys a protracted plasma concentration-time profile was observed at 40 mg/kg, characterized by a delayed T(max) (8-24 hr) and a long terminal half-life (6 hr). [3H]L-694,458 was well absorbed after oral dosing to rats at 10 mg/kg, as indicated by the high recovery of radioactivity in bile (83%) and urine (6%) of bile duct-cannulated rats. Only approximately 5% or less of the radioactivity in bile, urine, and feces was a result of intact L-694,458, indicating that the compound was being eliminated by metabolism, followed by excretion of the metabolites in feces, via bile. Demethylenation of the methylenedioxyphenyl group resulting in the catechol was the primary metabolic pathway in human and rhesus monkey liver microsomes. In rat liver microsomes, the major metabolite was the N-oxide of the methyl-substituted piperazine nitrogen. In rats dosed iv and orally with [3H]L-694,458, concentrations of radioactivity were highest in the lung (the primary target tissue), adrenals, and liver. L-694,458 was unstable in rat blood and plasma, degrading via a pathway believed to be catalyzed by B-esterases and to involve cleavage of the beta-lactam ring and loss of the methylpiperazine phenoxy group. In vitro studies indicated that in human liver, L-694,458 was metabolized by CYP3A and 2C isozymes, and in both monkey and human liver microsomes the compound acted as an inhibitor of testosterone 6beta-hydroxylation.     

Society stress and peptic ulcer perforation

To examine the relationship between society stress and peptic ulcer perforation, time-trend analysis was performed on the annual incidence of perforated peptic ulcer per 100,000 population in Hong Kong during the years 1962-85, when Hong Kong, as a developing city, went through significant socio-economic and political changes, and the trend was correlated with specially designed and validated society stress scores estimated annually during the same period. The society stress scores were derived independently by two expert panels blinded to the purpose of the study, one selecting and categorizing negative news events for Hong Kong during this period, and the other weighing the categories and scoring the impact of the news on Hong Kong. The incidence of perforation increased significantly during the years and manifested three distinct peaks, which coincided with the worst economic recession in Hong Kong, the influx of mainlander Chinese and Vietnamese boat people, and the Sino-British negotiation on the sovereignty of Hong Kong after 1997. Both linear and autoregression analysis, the latter taking into consideration point fluctuations in rates, showed that perforation rates correlated significantly with the society stress scores (r = 0.57, P < 0.002). The peak effects and the significant correlations indicate that an association exists between society stress and peptic ulcer perforation, and suggest that chronic society stress plays an important role in the aetiology of this condition, although the relatively low r value also suggests the presence of other aetiological factors.     

Arrhythmia detection and response in a monitoring technician and pocket paging system

Technologically advanced telemetry systems have begun to produce alternatives to the need for continuous visual observation of the electrocardiogram (ECG). Few studies have been conducted to determine the efficacy of these systems in the clinical setting. The purpose of this study was to describe two different approaches to communication of arrhythmia events and corresponding nurse response. One approach, on a cardiac medical unit, utilized a monitoring technician to continuously observe ECGs at a central monitoring technician station (MTS) and notify the nurse of changes. The other approach, on a general medical unit, eliminated the use of the monitoring technician and utilized a pocket paging system (PPS). The PPS interfaced with the computerized arrhythmia detection system from the ECG monitor, which directly alerted the nurse to arrhythmia events. A quasi-experimental comparative post-test design was used. The sample consisted of 50 randomly selected, 2-hour observation periods on each unit during a 3-month period. Data collectors recorded the interaction of the monitoring technician with the arrhythmia detection system and the nurse on the MTS unit, or the nurse using the PPS. Results of this study revealed all arrhythmia events activated an alarm by the computerized arrhythmia detection system. Length of time to notify the nurse was within 0 to 1 minute for both systems. This study demonstrated that the PPS is a viable approach to arrhythmia detection and communication in the medical/cardiac patient population.