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Biomedical subjects

M E King

Publications and source records attributed to M E King.

At least 19 recordsLinked to original sources

Concept, development, administration, and analysis of a certifying examination in echocardiography for physicians.

In 1993, the American Society of Echocardiography appointed a committee to develop an objective examination in echocardiography. In 1995, a pilot of this examination was administered, with operational examinations offered each year from 1996 to 1999. This report describes the development of the examination, including its underlying philosophy, the test itself, and the scoring process, and includes results from the first 4 examinations. To date, 1266 physicians have taken the examination, and roughly 60% of those have passed. The number of echocardiograms performed or interpreted each week had the largest effect on examination scores; the effects of both the amount of training and the practice discipline were small but significant. The evolution of the original committee and new directions for the testing organization are also discussed.

Certification↗

Oxidative regulation of fatty acid-induced tau polymerization.

Alzheimer's disease (AD) is characterized by the presence of amyloid-positive senile plaques and tau-positive neurofibrillary tangles. Aside from these two pathological hallmarks, a growing body of evidence indicates that the amount of oxidative alteration of vulnerable molecules such as proteins, DNA, and fatty acids is elevated in the brains of AD patients. It has been hypothesized that the elevated amounts of protein oxidation could lead directly to the formation of neurofibrillary tangles through a cysteine-dependent mechanism. We have tested this hypothesis in an in vitro system in which tau assembly is induced by fatty acids. Using sulfhydryl protective agents and site-directed mutagenesis, we found that cysteine-dependent oxidation of the tau molecule is not required for its polymerization and may even be inhibitory. However, by adjusting the oxidative environment of the polymerization reaction through the addition of a strong antioxidant or through the addition of an oxidizing system consisting of iron, adenosine diphosphate, and ascorbate, we found that oxidation does play a major role in our in vitro paradigm. The results indicated that fatty acid oxidation, the amount of which is found to be elevated in AD patients, can facilitate the polymerization of tau. However, "overoxidation" of the fatty acids can inhibit the process. Therefore, we postulate that specific fatty acid oxidative products could provide a direct link between oxidative stress mechanisms and the formation of neurofibrillary tangles in AD.

Actin Cytoskeleton↗

In vitro polymerization of tau protein monitored by laser light scattering: method and application to the study of FTDP-17 mutants.

Tau polymerization into the filaments that compose neurofibrillary tangles is seminal to the development of many neurodegenerative diseases. It is therefore important to understand the mechanisms involved in this process. However, a consensus method for monitoring tau polymerization in vitro has been lacking. Here we demonstrate that illuminating tau polymerization reactions with laser light and measuring the increased scattering at 90 degrees to the incident beam with a digital camera results in data that closely approximate the mass of tau polymer formation in vitro. The validity of the technique was demonstrated over a range of tau concentrations and through multiple angle scattering measurements. In addition, laser light scattering data closely correlated with quantitative electron microscopy measurements of the mass of tau filaments. Laser light scattering was then used to measure the efficiency with which the mutant tau proteins found in frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17) form filamentous structures. Several of these mutant proteins display enhanced polymerization in the presence of arachidonic acid, suggesting a direct role for these mutations in tau the filament formation that characterizes FTDP-17.

Chromosomes, Human, Pair 17↗

Closure of patent foramen ovale for paradoxical emboli: intermediate-term risk of recurrent neurological events following transcatheter device placement.

OBJECTIVES: We report the largest and the longest follow-up to date of patients who underwent transcatheter patent foramen ovale (PFO) closure for paradoxical embolism. BACKGROUND: Closure of a PFO has been proposed as an alternative to anticoagulation in patients with presumed paradoxical emboli. METHODS: Data were collected for patients following PFO closure with the Clamshell, CardioSEAL or Buttoned Devices at two institutions. RESULTS: There were 63 patients (46 +/- 18 years) with a follow-up of 2.6 +/- 2.4 years. Fifty-four (86%) had effective closure of the foramen ovale (trivial or no residual shunt by echocardiography) while seven (11%) had mild and two (3%) had moderate residual shunting. There were four deaths (leukemia, pulmonary embolism, sepsis following a hip fracture and lung cancer). There were four recurrent embolic neurological events following device placement: one stroke and three transient events. The stroke occurred in a 56-year-old patient six months following device placement. A follow-up transesophageal echocardiogram showed a well seated device without residual shunting. Two of the four events were associated with suboptimal device performance (one patient had a significant residual shunt and a second patient had a "friction lesion" in the left atrial wall associated with a displaced fractured device arm). The risk of recurrent stroke or transient neurological event following device placement was 3.2% per year for all patients. CONCLUSION: Transcatheter closure of PFO is an alternative therapy for paradoxical emboli in selected patients. Improved device performance may reduce the risk of recurrent neurological events. Further studies are needed to identify patients most likely to benefit from this intervention.

Adult↗

Differential assembly of human tau isoforms in the presence of arachidonic acid.

Six tau isoforms arise from the alternative splicing of a single gene in humans. Insoluble, filamentous deposits of tau protein occur in a number of neurodegenerative diseases, and in some of these diseases, the deposition of polymers enriched in certain tau isoforms has been documented. Because of these findings, we have undertaken studies on the efficacy of fatty acid-induced polymerization of the individual tau isoforms found in the adult human CNS. The polymerization of each tau isoform in the presence of two concentrations of arachidonic acid indicated that isoforms lacking N-terminal exons e2 and e3 formed small, globular oligomers that did not go on to elongate into straight (SF) or paired helical (PHF) filaments under our buffer conditions. The polymerization of all isoforms containing e2 or e2 and e3 occurred readily at a high arachidonic acid concentration. Conversely, at a lower arachidonic acid concentration, only tau isoforms containing four microtubule binding repeats assembled well. Under all buffer conditions employed, filaments formed from three of the isoforms containing e2 and e3 resembled SFs in morphology but began to form PHF-like structures following extended incubation at 37 degrees C. These results indicate that polymerization of the intact tau molecule may be facilitated by e2 and e3. Moreover, tau isoforms containing three versus four microtubule binding repeats display different assembly properties depending on the solvent conditions employed.

Actin Cytoskeleton↗

Fatigue patterns observed in patients receiving chemotherapy and radiotherapy.

The purpose of this study was to describe the patterns of cancer-related fatigue (CRF) and vigor in patients receiving chemotherapy or radiation therapy. Five studies that measured fatigue and vigor with the Profile of Mood States were used to describe the pattern of CRF and vigor during and after both types of treatment. Repeated-measures ANOVA was used to determine differences over time in each study. Results demonstrate different patterns of CRF for patients receiving chemotherapy and radiation therapy. Chemotherapy-related CRF peaks in the days after chemotherapy, whereas radiation therapy-related CRF gradually accumulates over the course of treatment. The CRF associated with both forms of treatment gradually declines over time. The prevalence, intensity, and persistence of CRF during treatment and for months after treatment is complete make this symptom one that cannot be ignored.

Adolescent↗

Ligand-dependent tau filament formation: implications for Alzheimer's disease progression.

The mechanism through which arachidonic acid induces the polymerization of tau protein into filaments under reducing conditions was characterized through a combination of fluorescence spectroscopy and electron microscopy. Results show that polymerization follows a ligand-mediated mechanism, where binding of arachidonic acid is an obligate step preceding tau-tau interaction. Homopolymerization begins with rapid (on the order of seconds) nucleation, followed by a slower elongation phase (on the order of hours). Although essentially all synthetic filaments have straight morphology at early time points, they interact with thioflavin-S and monoclonal antibody Alz50 much like authentic paired helical filaments, suggesting that the conformation of tau protein is similar in the two filament forms. Over a period of days, synthetic straight filaments gradually adopt paired helical morphology. These results define a novel pathway of tau filament formation under reducing conditions, where oxidation may contribute to final paired helical morphology, but is not a necessary prerequisite for efficient nucleation or elongation of tau filaments.

Alzheimer Disease↗

Ovulation, fertilization and lambing rates, and peripheral progesterone concentrations, in ewes inseminated at a natural oestrus during November or February.

The objective of this study was to determine the relative importance of seasonal changes in ovulation rate, fertilization rate and embryo survival as the cause of reduced lambing rates in ewes mated in February compared with those mated in November. The study was conducted at 57 degrees N using mature Mule ewes and Suffolk rams. Sixty ewes were allocated equally to five groups: unbred (UB) or mated at a natural oestrus during November (N) or February (F) by natural (N) or cervical artificial (A) insemination. Groups were maintained separately at pasture supplemented with hay. A raddled vasectomized or non-vasectomized ram was present with UB, NN and NA groups from 26 October 1995 to 1 January 1996 and with UB, FN and FA groups from 25 January 1996 to 31 March 1996. Ewes marked by the ram were recorded twice a day, and those in groups NN, NA, FN and FA were inseminated at their second behavioural oestrus. For all ewes, blood samples were obtained once a day from introduction of the vasectomized rams until 30 days after mating (groups NN, NA, FN and FA) or 20 days after the first oestrus (group UB), and ovulation rate was measured by laparoscopy 7 days after the first oestrus. For ewes in groups NN, NA, FN and FA, ovulation rate was measured again after the second oestrus and ova were recovered from six ewes per group for assessment of fertilization before autotransfer. Pregnancy and lambing rates were recorded at term. Mean (+/- SE) dates of the first recorded oestrus for ewes in groups NN, NA and UB, and FN, FA and UB were 4 +/- 1.1 November and 4 +/- 0.9 February, respectively, and intervals between the first and second oestrus were 16 +/- 0.2 and 17 +/- 0.3 days (P < 0.01), respectively. Ovulation rates were 2.6 +/- 0.08 and 2.0 +/- 0.05 (P < 0.001), and peripheral progesterone concentrations during the luteal phase were 8.5 +/- 0.25 and 7.6 +/- 0.31 ng ml-1 (P < 0.05), for November and February, respectively. The difference in peripheral progesterone concentration was not solely attributable to the difference in ovulation rate. There was no significant effect of month or method of insemination, or of embryo recovery and autotransfer procedures on pregnancy rates and the proportion of ewes that became pregnant were NN 0.92, NA 0.83, FN 0.67 and FA 0.75. For ewes undergoing embryo recovery and autotransfer, ova recovered per corpus luteum were 1.00, 0.93, 1.00 and 0.92, fertilized ova per ovum recovered were 0.69, 0.92, 1.00 and 0.83, and lambs born per corpus luteum were 0.62, 0.79, 0.78 and 0.58 for NN, NA, FN and FA groups, respectively. There were no significant seasonal effects on fertilization rate or embryo survival. It is concluded that a seasonal decline in ovulation rate is the primary cause of reduced lambing rates in ewes mated in February compared with those mated in November. Pregnancy rates were high after mating in both periods and were not enhanced by the use of cervical insemination.

Analysis of Variance↗

Tissue adhesives: a new method of wound repair.

Simple traumatic lacerations are one of the most common reasons for visits to the emergency department. Traditionally, wound repair has been performed using sutures. The use of tissue adhesives is an approved and popular alternative method of wound closure in several countries. Numerous published studies have found that, with appropriate use, repair of lacerations using tissue adhesives is faster, less painful, and more economical than suturing. Tissue adhesives result in fewer wound infections than suturing, and cosmetic outcomes have been comparable to or better than suturing. The newest product, 2-octylcyanoacrylate, received Food and Drug Administration approval in 1998 and is being marketed in the United States. The technique of wound repair with tissue adhesives is easily mastered and is a useful skill in the management of simple lacerations. This article provides a comprehensive review of the literature on the use of tissue adhesives and discusses them as an alternative to traditional methods of wound repair.

Adult↗

Relationship between % heart rate reserve and % VO2 reserve in treadmill exercise.

For exercise prescription purposes, it is often assumed that % heart rate reserve (%HRR) provides equivalent intensities to %VO2max. However, a recent study from this laboratory demonstrated that during cycling exercise %HRR is not equivalent to %VO2max, but is instead equivalent to a percentage of the difference between resting and maximal VO2, i.e., % VO2reserve (%VO2R). The current study examined these relationships during treadmill exercise. Fifty adults performed Bruce protocol treadmill tests to exhaustion. For each subject, data obtained at rest, at the end of each stage, and at maximum were used to determine linear regressions of %HRR versus %VO2max, and of %HRR versus %VO2R. For %HRR versus %VO2max the mean intercept and slope were -6.1+/-0.7 and 1.10+/-0.01, respectively, with a mean r of 0.990+/-0.002. For %HRR versus %VO2R, the mean intercept and slope were 1.5+/-0.6 and 1.03+/-0.01, respectively, with a mean r of 0.990+/-0.002. Both regressions differed statistically from the line of identity (i.e., intercept of 0 and slope of 1). However, the regression of %HRR versus %VO2R was significantly closer (P < 0.001 ) to the line of identity than was the regression of %HRR versus %VO2max. We conclude that %HRR should be considered as an indicator of %VO2R, not %VO2max, when prescribing treadmill exercise, as was previously concluded for cycling exercise.

Adolescent↗

Planning and conducting a multi-institutional project on fatigue.

PURPOSE/OBJECTIVES: To describe the process used in proposal development and study implementation for a complex multisite project on cancer treatment-related fatigue (CRF), identify strategies used to manage the project, and provide recommendations for teams planning multisite research. DATA SOURCES: Information derived from project team meeting records, correspondence, proposals, and personal recollection. DATA SYNTHESIS: The project was built on preexisting relationships among the three site investigators who then built a team including faculty, research coordinators, staff nurses, and students. Study sites had a range of organizational models, and the proposal was designed to capitalize on the organizational and resource strengths of each setting. Three team members drawn from outside oncology nursing provided expertise in measurement and experience with fatigue in other populations. Planning meetings were critical to the success of the project. Conference calls, fax technology, and electronic mail were used for communication. Flexibility was important in managing crises and shifting responsibility for specific components of the work. The team documented and evaluated the process used for multisite research, completed a major instrumentation study, and developed a cognitive-behavioral intervention for CRF. CONCLUSIONS: Accomplishments during the one-year planning grant exceeded initial expectations. The process of conducting multisite research is complex, especially when the starting point is a planning grant with specific research protocols to be developed and implemented over one year. Explicit planning for decision-making processes to be used throughout the project, acknowledging the differences among the study settings and planning the protocols to capitalize upon those differences, and recruiting a strong research team that included a member with planning grant and team-building expertise were essential elements for success. IMPLICATIONS FOR NURSING PRACTICE: Specific recommendations for others planning multisite research are related to team-building, team membership, communication, behavioral norms, role flexibility, resources, feedback, problem management, and shared recognition.

Communication↗

Two-dimensional echocardiographic assessment of the progression of aortic root size in 127 patients with chronic aortic regurgitation: role of the supraaortic ridge and relation to the progression of the lesion.

Although aortic root dilation has etiologic and prognostic significance in patients with chronic aortic regurgitation (AR), no information is available regarding changes over time in aortic root size in patients with the entire spectrum of AR severity or how such changes relate to progression of the AR or to left ventricular (LV) overload. To analyze this, a total of 127 patients with chronic AR who had more than 6 months of follow-up by two-dimensional and Doppler echocardiography were included in the study (69 men and 58 women; mean age 59.3 +/- 21.2 years [range 14 to 94 years]; 67 cases of mild, 45 moderate, 15 severe, and 21 bicuspid aortic valve disease). The aortic anulus, sinuses of Valsalva, supraaortic ridge, and ascending aorta were measured in the parasternal long-axis view, LV volumes were calculated (biplane Simpson's approach), and the severity of AR was quantified based on proximal jet size and graded according to an algorithm that takes into account major color Doppler criteria. At entry to the study, significant differences between patients with mild, moderate, and severe AR were noted only in supraaortic ridge size (1.46 +/- 0.29 cm/m2 vs 1.63 +/- 0.33 cm/m2 [p < 0.006]; vs 1.67 +/- 0.43 cm/m2 [p < 0.03]). A significant increase in aortic root size at all levels was observed during the follow-up period in all three groups of severity of AR. The rate of change of the supraaortic ridge, the upper support structure of the anulus and cusps, was faster in patients with more severe degrees of AR (p = 0.013); this was not the case at the other aortic levels. No differences were observed in aortic root size or rate of progression between patients with bicuspid or tricuspid aortic valves. Patients were considered "progressive" if they lay on the steepest positive segment of the curve representing the rank order in the rate of aortic root progression. Compared with "nonprogressive" patients, patients who were progressive in supraaortic ridge size (rate >0.12 cm/yr; n = 23) had a faster rate of progression in the degree of regurgitation as assessed by the regurgitant jet area/LV outflow tract area ratio measured in the parasternal short-axis view (0.48 +/- 0.45 vs 0.24 +/- 0.5/yr; p < 0.03) and a foster rate of progression of LV end-diastolic volume (30 +/- 22.8 vs 14.4 +/- 15.6 ml/yr; p < 0.0002) and LV mass (70.8 +/- 74.4 vs 16.8 +/- 19.2 gm/yr; p < 0.0004). In conclusion, there is progressive dilation of the aortic root at all levels, even in patients with mild AR. More rapid progression in aortic root size is associated with more rapid progression of the underlying aortic insufficiency, as well as more rapid increases in LV volume and mass.

Adolescent↗

Quantitative assessment of stenotic aortic valve area by using intracardiac echocardiography: in vitro validation and initial in vivo illustration.

Quantitative assessment of aortic stenosis (AS) is subject to the limitations of all current noninvasive and invasive methods. The ability to obtain a direct measure of aortic valve area with high resolution by intracardiac echocardiography (ICE) could be of great benefit to catheterized patients. To provide a fixed AS area as an ideal standard for comparison, we performed ICE in 12 sheep hearts with experimentally created AS and five human AS hearts from autopsies. ICE catheters were passed retrograde across the aortic valve, and the minimal orifice area on pullback was planimetered and compared with calibrated video imaging. The entire orifice circumference could be successfully recorded in 16 (94%) hearts. Orifice area from ICE correlated well with actual values (r=0.98; standard error of the estimate [SEE] = 0.06 cm2). To illustrate the applicability in vivo, two canine models and 10 patients with AS were studied. The limiting orifice could be imaged in both animals and in 8 of 10 patients, in whom values agreed well with invasive data (r= 0.95; SEE = 0.04 cm2). ICE can therefore accurately measure AS orifice area in vitro; it can be applied in vivo as well. These validation studies laid the foundation for subsequent clinical studies and applications.

Animals↗

Apparent versus real exposures of nuclear medicine technologists during aerosol lung ventilation scanning.

The exposure of nuclear medicine technologists to airborne radiocontaminants is generally far below the compliance limits. Most of the contamination is external rather than internal deposition. Higher contamination levels approaching the allowable limits are rare. Personal respiratory protection is unwarranted and may have undesirable impressions on patients undergoing lung scanning. Exposures are well controlled by suitable work practices that are in keeping with as low as reasonably achievable (ALARA) principles.

Aerosols↗

Use of epidemiologic principles to identify risk factors associated with the development of diarrhea in calves in five beef herds.

The objective of the study reported here was to identify and measure risk factors associated with the incidence of diarrhea in calves in 5 beef herds in North Dakota. Risk factors associated with calves developing diarrhea during the 1992 calving season were used to develop the following intervention strategies that were implemented during 1993: heifers calved in a separate location, diarrheal calves and their dams were placed in a quarantine area, and pregnant cattle were fed a diet supplemented with protein and copper. The risk of calves developing diarrhea was 5 times higher during the first year, compared with the second year, suggesting that the management changes made during the second year were contributing factors in reducing the percentage of calves with diarrhea. The risk of diarrhea developing in calves born to heifers was 3.9 times greater than that in calves born to cows. Analysis of our data indicated that the use of an epidemiologic approach can identify risk factors, which can lead to the development of intervention procedures that may decrease the incidence of diarrhea in calves in beef herds.

Animals↗

Intracardiac ultrasonographic assessment of atrial septal defect area: in vitro validation and technical considerations.

Assessment of atrial septal defect (ASD) size and shape is important for planning and guiding its transcatheter occlusion and can potentially be achieved by intracardiac ultrasonography (ICUS). ICUS accuracy, however, must first be established against stable standards and technical imaging requirements defined. We therefore used 10, 20, and 30 MHz ICUS catheters to examine 17 ASDs that were 0.16 to 6.7 cm2 in area and were surgically created in excised ovine hearts with 10, 20, and 30 MHz ICUS catheters. ASD shape and area by ICUS were compared with direct video images of the actual ASD. In all instances minimal area by ICUS pullback agreed well with actual values (y = 1.04x + 0.2, SEE = 0.23 cm2, r = 0.99) and corresponded well with defect shapes. The maximum angle between ultrasonography beam and septal plane allowing for complete ASD visualization was 20 degrees. The angle depended on transducer frequency and septal thickness. This new technique has potential value for the accurate assessment of ASD shape and size and may be especially useful in the setting of transcatheter occlusion.

Animals↗