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Biomedical subjects

D Carlson

Publications and source records attributed to D Carlson.

At least 19 recordsLinked to original sources

Lack of Borrelia burgdorferi DNA in synovial samples from patients with antibiotic treatment-resistant Lyme arthritis.

OBJECTIVE: To determine whether Borrelia burgdorferi DNA may be detected in synovial tissue from patients with Lyme arthritis who have persistent synovial inflammation after antibiotic treatment. METHODS: Synovial specimens obtained at synovectomy from 26 patients with antibiotic treatment-resistant Lyme arthritis and from 10 control subjects were tested for B burgdorferi DNA using 3 primer-probe sets that target genes encoding outer surface proteins A or B or a flagellar protein (P41) of the spirochete. RESULTS: The 26 patients with Lyme arthritis, who had received antibiotic therapy for a mean total duration of 8 weeks prior to synovectomy, and the 10 control subjects each had negative polymerase chain reaction (PCR) results in synovial samples. When the samples were spiked with approximately 1-10 B burgdorferi, all but 1 had positive PCR results, suggesting that spirochetal DNA could have been detected in most of the unspiked samples if it had been present. CONCLUSION: These results indicate that synovial inflammation may persist in some patients with Lyme arthritis after the apparent eradication of the spirochete from the joint with antibiotic therapy.

Adolescent

Morphological and biochemical responses of Bacillus subtilis to selenite stress.

When introduced into a chemically defined minimal medium supplemented with 1 mM sodium selenite (79 ppm Se(o)), Bacillus subtilis was found to undergo a series of morphological and biochemical adaptations. The morphological changes included the formation of "round bodies" associated with the detoxification of selenite to elemental selenium. Round bodies observed transiently were not apparent during balanced growth of cells adapted previously to selenite-containing medium. Under balanced growth conditions, cell structures similar to "round bodies", could be produced by treating cells with lysozyme. The selenite-induced structural alterations in cells were accompanied by an increase in the content of thioredoxin and the associated enzyme, NADP-thioredoxin reductase. The results suggest that the biovalence transformation of high levels of selenite may involve a dithiol system.

Bacillus subtilis

Comparison of absorbable and nonabsorbable sutures for microsurgical vasovasostomy in rats.

OBJECTIVES: At least 12% of initially patent vasovasostomies (VVs) shut down. Currently, only nonabsorbable sutures are used for VV. A synthetic, slowly absorbing, monofilament polyglactin suture has been developed that retains tensile strength for up to 6 months. We performed a prospective controlled randomized study comparing absorbable and nonabsorbable sutures for rat VVs. METHODS: Bilateral microsurgical VV was performed in three groups of 36 Wistar male rats, with 10-0 nylon, 10-0 polypropylene, and 10-0 polyglactin sutures. Twelve control rats underwent sham operations. Three rats in each group were killed at 2, 6, 12, and 24 weeks. The abdominal end of the vas deferens was transected and the intraluminal fluid examined microscopically for presence of sperm. The segment of the vas deferens containing the anastomosis was excised. Fluid from the testicular end was examined for sperm to confirm spermatogenesis. Patency was confirmed by an antegrade indigo carmine vasogram of the anastomotic segment. Segments were randomly sent for histologic or tensile strength evaluation. RESULTS: The mean tensile strength of the anastomoses performed with nylon was slightly higher than in polypropylene and polyglactin sutures, although the difference was not statistically significant. Polyglactin consistently maintained tensile strength throughout 6 months without significant fluctuations. The mean patency rate in the polyglactin group was 96%, in nylon 81%, and in polypropylene 61%. Although polyglactin had a consistently higher patency rate compared with nonabsorbable sutures, the difference was not statistically significant (P = 0.11) but indicated a strong trend. The occurrence of microscopic sperm granuloma, muscle layer injuries, intimal fibrosis, and adventitial fibrosis of the vas deferens was not significantly different between suture types. CONCLUSIONS: The three suture materials appear equivalent with respect to overall tensile strength of anastomosis; with histologic evaluation, the trend was toward better patency with polyglactin. Polyglactin 10-0 microsurgical suture is a viable alternative to nonabsorbable sutures in microsurgical VVs, although further studies are indicated to assess long-term results.

Animals

Inadvertent ketamine overdose in children: clinical manifestations and outcome.

STUDY OBJECTIVE: We sought to characterize the clinical manifestations, outcome, and etiology of inadvertent ketamine overdose in the emergency department. METHODS: We investigated cases of inadvertent ketamine overdose in children seen in the ED solicited through electronic mail subscription lists or reported to the Institute for Safe Medication Practices. The clinical manifestations, outcome, and reported cause for each case are described. RESULTS: We identified 9 cases of inadvertent ketamine overdose in children treated in the ED. Patients received either 5(n=3), 10(n=5), or 100(n=1) times the intended dose, either by the intramuscular (n=5) or intravenous (n=4) route. All 9 experienced prolonged sedation (3 to 24 hours). Four experienced brief respiratory depression shortly after administration, and assisted ventilation was performed in 2. Two children without respiratory difficulty or hypoxemia were intubated by their physicians as a precaution. In 5 children, the dosing error was not discovered until late in the sedation, often when the child was not waking at the expected time. No adverse outcomes were noted, and all children were normal neurologically on discharge and longer-term follow-up if available. CONCLUSION: No adverse outcomes were noted in 9 healthy children treated in the ED who inadvertently received 5 to 100 times the intended dose of ketamine. Toxicity manifested as prolonged sedation in all 9 and brief respiratory depression in 4. The margin of safety in ketamine overdose may be wide, although less common and more serious outcomes cannot be excluded by this small, self-reported sample.

Anesthetics, Dissociative

Ovarian steroids and stress produce changes in peripheral benzodiazepine receptor density.

Although past research has described changes in the density of the peripheral benzodiazepine receptor in brain and in peripheral organs in response to stressors and steroid hormone exposure, their combined influence had yet to be determined. This study examined the effect of swim-stress as a function of ovarian hormone administration on the binding of an isoquinoline carboxamide derivative, [3H]PK 11195, in brain and peripheral tissues. In olfactory bulb and adrenal gland, stress increased peripheral benzodiazepine receptor density in ovariectomized rats with and without estradiol and progesterone replacement injection, even when compared with unstressed animals treated with hormones, where estradiol + progesterone decreased peripheral benzodiazepine receptor number in olfactory bulb, but estradiol and estradiol + progesterone increased it in adrenal gland. In frontal cortex, stress decreased peripheral benzodiazepine receptor number, an effect that was reversed by estradiol. In hippocampus estradiol decreased peripheral benzodiazepine receptor density in unstressed animals and estradiol + progesterone decreased peripheral benzodiazepine receptor number in unstressed and stressed animals. In cerebellum, stress, estradiol and estradiol + progesterone alone decreased peripheral benzodiazepine receptor density. In uterus of unstressed controls, estradiol + progesterone increased peripheral benzodiazepine receptor density, and stress produced a further increase in steroid-treated females. Stress did not affect peripheral benzodiazepine receptor density in kidney, except in animals that received estradiol + progesterone injections, where swim-stress produced a significant decrease in peripheral benzodiazepine receptor density. Thus, steroid hormones regulate peripheral benzodiazepine receptor density in endocrine organs and brain, and the hormonal state of the organism modifies the peripheral benzodiazepine receptor response to stress in a tissue- and brain region-specific manner, suggesting that the peripheral benzodiazepine receptor may play a pivotal role in an integrated response to stress.

Adrenal Glands

Use of an engineered ribozyme to produce a circular human exon.

We report the use of an engineered ribozyme to produce a circular human exon in vitro. Specifically, we have designed a derivative of a yeast self-splicing group II intron that is able to catalyze the formation of a circular exon encoding the first kringle domain (K1) of the human tissue plasminogen activator protein. We show that the circular K1 exon is formed with high fidelity in vitro. Furthermore, the system is designed such that the circular exon that is produced consists entirely of human exon sequence. Thus, our results demonstrate that all yeast exon sequences are dispensable for group II intron catalyzed inverse splicing. This is the first demonstration that an engineered ribozyme can be used to create a circular exon containing only human sequences, linked together at a precise desired ligation point. We expect these results to be generalizable, so that similar ribozymes can be designed to precisely create circular derivatives of any nucleotide sequence.

Catalysis

Development of fatigue symptoms during simulated driving.

Why do people sometimes allow themselves to be overcome by fatigue? Ancient human survival may have depended on ignoring fatigue. Its modern occurrence in the absence of strain may further render us insensitive to its warning value. To test whether deliberate monitoring of certain symptoms may help drivers and other workers realize when they need to rest to avoid hazard, the development of fatigue while driving a simulator was objectively measured in terms of how many persons quit driving as a function of time. Some subjects asked to stop after 90 minutes; others lasted 240 minutes. Grouping data from an adapted Pearson [(1957) Journal of Applied Psychology, 44, 186-191] fatigue checklist revealed a curious phenomenon. No matter how long subjects drove before wanting to quit, they still developed much the same subjective level of fatigue at the end. This suggests that people do not differ greatly in how much fatigue they can tolerate but rather how quickly they reach a certain critical level of fatigue. Averaging fatigue scores backwards from the time subjects quit produced a function similar to the quitting function. Similar treatment of the other data revealed certain clusters of symptoms whose development also paralleled the development of fatigue.

Adolescent

Sleep in the laboratory and sleep at home: comparisons of older insomniacs and normal sleepers.

Many laboratory polysomnographic (LPSG) studies have shown only modest sleep differences between insomniacs and matched, noncomplaining normal controls. However, the extent to which LPSG methodology affects the outcome of such comparisons has yet to be tested. In the current investigation, 32 (16 females, 16 males) older (age > or = 60 years) insomniacs and an age-matched and gender-matched sample of 32 noncomplaining normal sleepers underwent three consecutive nights of LPSG monitoring and another three consecutive nights of PSG monitoring in their homes (HPSG). By random assignment, one-half of the subjects in each group underwent LPSG first, whereas the remaining subjects underwent HPSG first. Each PSG recording was blindly scored using conventional scoring criteria, and resulting measures of total sleep period, total sleep time, sleep efficiency percent, stage 1 time, slow-wave sleep time, and rapid eye movement latency were used to compare the two subject groups within each PSG recording site (i.e. lab and home). Statistical analyses showed the normals sleepers and insomniacs evidenced similar pronounced first night effects (FNEs) when undergoing LPSG. However, neither mean values of the selected sleep parameters nor measures reflecting their night-to-night variability differentiated the insomniacs from the normal sleepers when such measures were derived from LPSG. In contrast, FNEs were generally absent for both subject groups when they underwent HPSG. Moreover, the insomniacs displayed significantly greater variability in several of their sleep measures during HPSG than did the normal sleepers. Overall, results suggest FNEs are a concern mainly when using LPSG, and HPSG may be more sensitive than LPSG for documenting sleep differences between normal sleepers and insomniacs. Additional studies are needed to determine if the findings reported herein are similar for young and middle-aged adults.

Aged

Do our methods lead to insomniacs' madness?: Daytime testing after laboratory and home-based polysomnographic studies.

Complaints of daytime dysfunction are common among chronic insomniacs, but laboratory comparisons of insomniacs and age-matched and gender-matched normal controls have generally failed to document these complaints. However, a few studies, which allowed subjects to sleep in their homes on the nights before daytime testing, have shown some relative diurnal deficits among insomniacs. The current study compared the effects of nocturnal laboratory and home polysomnogram (PSG) studies on subsequent daytime test results among older insomniacs and normal sleepers. Insomniacs (n = 32) and normal sleepers (n = 32) were randomly assigned to first undergo three nights of nocturnal PSG monitoring either in the sleep laboratory (16 insomniacs, 16 normal sleepers) or in their homes (16 insomniacs, 16 normal sleepers). Following the third night of PSG monitoring, subjects spent 1 day in the sleep laboratory, where they completed a four-trial multiple sleep latency test along with four trials of a computer-administered performance test battery. Results showed that insomniacs, as a group, were slightly, albeit consistently, sleepier than were normal sleepers following nights of home sleep monitoring, but a reverse of this trend was found among subjects who underwent nocturnal laboratory PSG before daytime testing. Furthermore, normal sleepers showed faster reaction times on a signal detection task than did insomniacs within the subgroup who underwent home PSGs prior to such testing. However, within the subgroup that underwent nocturnal laboratory PSGs, insomniacs' signal detection reaction times were significantly faster than those shown by normal sleepers. Results provide some support for the speculation that the nocturnal PSG monitoring site, used as a precursor to daytime testing, may systematically affect daytime comparisons between insomniacs and matched controls. Moreover, these results suggest that the use of home-based nocturnal PSG monitoring prior to daytime testing may provide an enhanced understanding of insomniacs' diurnal complaints.

Aged

IS outlook '96: predictions & predilections. Roundtable discussion.

Musings from some of the leading national and international HIT organizations make it clear that the need for a computer-based patient record is approaching the critical point. Half of our respondents identified the CPR as the single most important technology in 1996. One of our participants goes so far as to say that the era prior to the electronic medical record will one day be remembered as the "paper age." Progress in the development of standards--crucial to the CPR--could be dramatic this year, say experts from two of the major standards organizations. For a look at these issues and others, including key government policies to watch this year, read on.

Computer Communication Networks

Standardization of clinical decision making for the conduct of credible clinical research in complicated medical environments.

The likelihood that past experience will produce correct guides to current practice depends on the signal-to-noise ratio for the clinical problem of interest. If the signal-to-noise ratio is high, the decision will be sound and patient benefit likely to occur. If the signal-to-noise ratio is low, as is commonly the case with difficult clinical decisions, then personal experience and the best intentions will not assure sound clinical decisions. When the probability of benefit cannot be quantified, clinicians in complex settings are in danger of being misled by data and experience. Quantifiable probabilities established by group experiment or observation will be necessary for clinical decisions that can be expected to confer benefit on the patient. Explicit methods are necessary for interventions that can be replicated in experiments or in practice. Computerized protocols force the articulation of explicit clinical care methods and standardize clinical decision making. We have developed explicit, rule-based protocols, implemented them in our hospital, exported them to other hospitals, and successfully achieved a rigorous experimental environment in the clinical ICU. Exportation of such explicit methods may narrow the gap between efficacy (university hospital) and effectiveness (community hospital) research results.

Clinical Trials as Topic

Verification & validation algorithms for data used in critical care decision support systems.

A decision support system is only as good as the data generating that decision support system. If the data is incorrect, doesn't relate to the other pieces of data, is missing or is not consistent, the decision support system conclusions may be incorrect and inconsistent. While collecting data from several sites during a multicenter randomized clinical trial, we found that some critical data elements were missing, out of correct ranges, totally illogical, and/or inconsistently recorded. In order to get consistent, correct, and dependable information from a our decision support system, the data elements used in that system had to be checked for completeness, valid values, consistent units of measurement, and relationships to other items. Development of data quality assurance rules and the application of those rules is imperative to using the data to generate daily scores for multiple organ failure, sepsis, and barotrauma.

Algorithms

Medical informatics academia and industry: a symbiotic relationship that may assure survival of both through health care reform.

There are often clear lines drawn identifying the demilitarized zone between medical informatics academics and industry. Academics were "pure" intellectuals sequestered in ivory towers that effectively shielded them from the realities of the world. Industry has historically focused on creating effective products that produce financial return to the corporation. Both the paradigms of academia and industry are quickly becoming dinosaurs in the era of health care reform where both medical informatics academia and industry are under increasing pressure to develop and prove that medical informatics has a positive impact on health care both in terms of the quality of care as well as cost. Unfortunately, neither academia or industry alone are going to be able to successfully complete this task. The purpose of this paper is to describe such a collaborative effort that has produced a computerized decision support system for the management of mechanical ventilation in patients with the Adult Respiratory Distress Syndrome (ARDS) that is now installed and supported on three different commercial CIS platforms. This collaborative effort has allowed us to successfully mount a large multi-center clinical trial designed to determine efficacy.

Clinical Protocols