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Biomedical subjects

K E Cullen

Publications and source records attributed to K E Cullen.

35 records · Page 2Linked to original sources

Interaction between transcription regulatory regions of prolactin chromatin.

The regulation of transcription requires complex interactions between proteins bound to DNA sequences that are often separated by hundreds of base pairs. As demonstrated by a nuclear ligation assay, the distal enhancer and the proximal promoter regions of the rat prolactin gene were found to be juxtaposed. By acting through its receptor bound to the distal enhancer, estrogen stimulated the interaction between the distal and proximal regulatory regions two- to threefold compared to control values. Thus, the chromatin structure of the prolactin gene may facilitate the occurrence of protein-protein interactions between transcription factors bound to widely separated regulatory elements.

Animals↗

Firing behavior of brain stem neurons during voluntary cancellation of the horizontal vestibuloocular reflex. I. Secondary vestibular neurons.

1. The single-unit activity of vestibular neurons was recorded in alert squirrel monkeys. The monkeys had been trained to track a small visual target by generating smooth pursuit eye movements and to cancel their vestibuloocular reflex (VOR) by fixating a head stationary target. The monkeys were seated on a vestibular turntable, and their heads were held in the plane of the horizontal semicircular canals. The responses of 45 type I vestibular neurons whose activity was related to ipsilateral horizontal head movements were recorded. In 19 of 30 cells tested, electrical stimulation (0.1-ms monophasic pulses, < or = 800 microA) of the ipsilateral vestibular nerve evoked a spike at a monosynaptic latency (0.7-1.3 ms). 2. The spiking behavior of each cell was recorded during several behavioral paradigms: 1) spontaneous eye movements, 2) horizontal smooth pursuit of a target that was moved sinusoidally +/- 20 degrees/s at 0.5 Hz, 3) horizontal VOR during 0.5-Hz sinusoidal turntable rotations +/- 40 degrees/s (VORs), and 4) voluntary cancellation of the sinusoidal VOR by fixation of a head-stationary target during 0.5-Hz sinusoidal turntable rotation at +/- 40 degrees/s in the light (VORCs). 3. The response of most (34) of the units was recorded during unpredictable 100-ms steps in head acceleration (400 degrees/s2) that were generated while the monkey was fixating a target light. The acceleration steps were generated either when the monkey was stationary (VORt paradigm) or when the turntable was already rotating, and the monkey was canceling its VOR (VORCt paradigm). Smaller eye movements were evoked when the acceleration step was generated during VOR cancellation. 4. Type I vestibular units were grouped into two classes on the basis of the relationship of their firing rate to eye movements. The discharge rate of 20 "pure vestibular" units was not clearly related to eye movements. The remaining 25 units were classified as position-vestibular-pause (PVP) neurons. PVP neurons increased their firing rate during contralateral eye movements and during ipsilateral turntable rotations, and paused during saccadic eye movements. 5. Most (17/20) pure vestibular neurons generated the same response to vestibular stimuli when the monkeys canceled their VOR as they did during the VOR in both the sinusoidal and acceleration step paradigms. 6. The head velocity sensitivity of most (19/24) PVP neurons was reduced by 20-60% during VORCs, compared with their response during the VORs. The PVP neurons whose sensitivity of head movements was reduced during VORCs also exhibited a reduced vestibular sensitivity during VORCt.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Firing behavior of brain stem neurons during voluntary cancellation of the horizontal vestibuloocular reflex. II. Eye movement related neurons.

1. The single-unit activity of neurons in the vestibular nucleus, the prepositus nucleus, and the abducens nucleus, whose activity was primarily related to horizontal eye movements, was recorded in alert squirrel monkeys that were trained to track a small visual target by generating smooth pursuit eye movements and to cancel their horizontal vestibuloocular reflex (VOR) by fixating a head stationary target. 2. The spiking behavior of each cell was recorded during 1) spontaneous eye movements, 2) horizontal smooth pursuit of a target that was moved sinusoidally +/- 20 degrees/s at 0.5 Hz, 3) horizontal VOR evoked by 0.5-Hz sinusoidal turntable rotations +/- 40 degrees/s (VORs), and 4) voluntary cancellation of the VOR by fixation of a head-stationary target during 0.5-Hz sinusoidal turntable rotation at +/- 40 degrees/s (VORCs). The responses of most (28/42) of the units were recorded during unpredictable 100-ms steps in head acceleration (400 degrees/s2) that were generated while the monkey was fixating a target light. The acceleration steps were generated either when the monkey was stationary or when the turntable was already rotating (VORt trials), and the monkey was canceling its VOR (VORCt trials). 3. The firing behavior of all 12 of the abducens neurons recorded was closely related to horizontal eye position and eye velocity during all of the behavioral paradigms used, although there was a small but significant increase in the eye position sensitivity of many of these units when the eye was moving (smooth pursuit) versus when the eye was stationary (fixation). 4. Many neurons in the prepositus nucleus and the medial vestibular nucleus (n = 15) were similar to abducens neurons, in that their firing rate was related primarily to horizontal eye position and eye velocity, regardless of the behavioral paradigm used. These cells were, on average, more sensitive to eye position and smooth pursuit eye velocity than were abducens neurons. 5. The firing rate of 15 other neurons in the prepositus and medial vestibular nucleus was related primarily to horizontal smooth pursuit eye movements. The tonic firing rate of all of these smooth pursuit (SP) cells was related to horizontal eye position, and the majority generated bursts of spikes during saccades in all directions but their off direction. Six of the SP neurons fired in phase with ipsilateral eye movements, whereas the remaining nine were sensitive to eye movements in the opposite direction.(ABSTRACT TRUNCATED AT 400 WORDS)

Abducens Nerve↗

Gaze-related activity of putative inhibitory burst neurons in the head-free cat.

1. Previous studies in the cat have demonstrated that output neurons of the superior collicular as well as brain stem omnipause neurons have discharges that are best correlated, not with the trajectory of the eye in the head but, with the trajectory of the visual axis in space (gaze = eye-in-head + head-in-space) during rapid orienting coordinated eye and head movements. In this study, we describe the gaze-related activity of cat premotor "inhibitory burst neurons" (IBNs) identified on the basis of their position relative to the abducens nucleus. 2. The firing behavior of IBNs was studied during 1) saccades made with the head stationary, 2) active orienting combined eye-head gaze shifts, and 3) passive movements of the head on the body. IBN discharges were well correlated with the duration and amplitude of saccades made when the head was stationary. In both head-free paradigms, the behavior of cat IBNs differed from that of previously described primate "saccade bursters". The duration of their burst was better correlated with gaze than saccade duration, and the total number of spikes in a burst was well correlated with gaze amplitude and generally poorly correlated with saccade amplitude. The behavior of cat IBNs also differed from that of previously described primate "gaze bursters". The slope of the relationship between the total number of spikes and gaze amplitude observed during head-free gaze shifts was significantly lower than that observed during head-fixed saccades. 3. These studies suggest that cat IBNs do not fit into the categories of gaze-bursters or saccade-bursters that have been described in primate studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Abducens Nerve↗

Responses of vestibular and prepositus neurons to head movements during voluntary suppression of the vestibuloocular reflex.

Neurons in the vestibular nuclei and the prepositus nucleus exhibited several different types of changes in their firing behavior during voluntary cancellation of the horizontal VOR. The head velocity sensitivity of type I position-vestibular-pause neurons was reduced during cancellation, while type II vestibular neurons exhibit an increase in their sensitivity. The firing behavior of burst tonic neurons in the medial vestibular nucleus, the prepositus nucleus, like the cells in the abducens nucleus, was closely related to the eye movements generated when the VOR is cancelled. Other cells in the PH and MVN respond primarily to smooth pursuit eye movements. We suggest that the behavior of abducens neurons during the VOR and during VOR cancellation can be explained if they receive inputs from PVP neurons, burst tonic neurons, and smooth pursuit neurons.

Animals↗

Microtubules grow and shorten at intrinsically variable rates.

Microtubules were assembled from pure tubulin with axonemal pieces serving as nuclei. They were observed by video-enhanced differential-interference-contrast light microscopy. Their lengths were measured from videotaped images at frequent intervals (0.13-5 s). Error analysis indicated that the uncertainty in measuring a single length was quite small; the 95% confidence limit approximated the microscope's limit of resolution. Rates of growth and shortening of the dynamically unstable microtubules, obtained from the length-versus-time data, were found to be highly variable. The variability was far too large to be attributed to known random error of measurement and must be a property of the microtubules. Further experiments were aimed at finding its structural cause. The variability of rates exhibited by a single microtubule was as great as that of the whole population. The locations at which a growing microtubule changed its rate of growth were not related to the locations at which rates changed during its subsequent shortening. The cause of the variability must therefore be both small relative to the size of a microtubule and transient relative to its lifetime. Fluctuations in configuration of the microtubule's cap appear to be the likeliest source.

Animals↗

A non-visual mechanism for voluntary cancellation of the vestibulo-ocular reflex.

Squirrel monkeys were trained to cancel their vestibulo-ocular reflex (VOR) by fixating a visual target that was head stationary during passive vestibular stimulation. The monkeys were seated on a vestibular turntable, and their heads were restrained. A small visual target (0.2 degrees) was projected from the vestibular turntable onto a tangent screen. The monkeys' ability to suppress their VOR by fixating a head stationary target while the turntable was moving was compared to their ability to pursue the target when it was moved in the same manner. Squirrel monkeys were better able to suppress their VOR when the turntable was moved at high velocities than they were able to pursue targets that were moving at high velocities. The gaze velocity gain during VOR cancellation began to decrease when the head velocity was above 80 degrees/s, and was greater than 0.6 when the head velocity was above 150 degrees/s. However, gaze velocity gain during smooth pursuit decreased significantly when the target velocity was greater than 60 degrees/s, and was less than 0.4 when the target velocity was 150 degrees/s or more. The latency of VOR suppression was significantly shorter than the latency of smooth pursuit while the monkey was cancelling its VOR. When an unpredictable step change in head acceleration was generated while the monkey was cancelling its VOR, the VOR evoked by the head acceleration step began to be suppressed shortly after the initiation of the step (approximately 30 ms). On the other hand, the latency of the smooth pursuit eye movement elicited when the visual target was accelerated in the same manner during VOR cancellation was approximately 100 ms. The comparison between these two results suggests that the monkeys did not use visual information related to target motion to suppress their VOR at an early latency. The monkeys' ability to suppress the VOR evoked by an unexpected change in head acceleration depended on the size of the head acceleration step. The VOR evoked by unexpected step changes in head acceleration was progressively less suppressed at an early latency as the size of the acceleration step increased, and was not suppressed at an early latency when the step change in head acceleration was greater than 500 degrees/s2. During smooth pursuit eye movements, unexpected step changes in head acceleration evoked a VOR that was suppressed at an early latency (approximately 50 ms) if the head movement was in the same direction as the ongoing smooth pursuit eye movement.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Social and health policy issues in total joint replacement surgery.

Total joint replacement has restored function and provided comfort to many patients who would otherwise have suffered. However, success and widespread diffusion of this procedure pose a number of important questions. The patient's and the doctor's criteria of success may not be the same: Which are to be used? Health resources are becoming limited: Should money be spent to restore function and for pain relief to those late in life or past their work life? Who makes this choice? A medical technology is tested in the best of settings but routinely practiced in many: How should society and health care professionals monitor the results of surgery? Who should do surgery and where should it be done?

Health Resources↗

Effects of reducing physical therapy services on outcomes in total joint arthroplasty.

A natural experiment provided an opportunity to determine whether physical therapy (PT) service reduction would affect the outcomes of total joint arthroplasty. A sample of 200 patients with rheumatoid arthritis or osteoarthritis who underwent total hip or total knee replacement during successive reduction of services was randomly selected. The demographic and clinical characteristics of patients in each period were similar. Despite large differences between groups in hours of PT per patient, there were no major differences in length of stay between the groups, or compared to similar hospitals, functional status at discharge, or numbers of surgical complications. Implications for health services organization are discussed.

Aged↗

Cost-effectiveness of total joint arthroplasty in osteoarthritis.

Although total joint replacement (TJR) is a major advance in the treatment of patients with osteoarthritis, its cost-effectiveness has been questioned. We report the results of a study of the costs and benefits of TJR in consecutive osteoarthritis patients, 6 months after the surgery. Health status was measured by the Index of Well-Being. Costs of services for arthritis were determined by interview and billing records. Six months after TJR, significant improvements were seen in global health and in functional status. The average cost of care for the 6 months prior to TJR was $933. The average cost during the 6 months beginning with the TJR was $22,730 per patient--due almost entirely to costs of surgery. In general, the surgery did not change work status, probably because the mean age of the patients was 66.4 years. There were large effectiveness/cost differentials (the larger the effectiveness/cost differential, the higher the degree of cost-effectiveness [CE]). At 6 months, for all patients, the CE was associated with initial health status. The highest CE was observed in 10 patients who initially had the poorest health. TJR is more cost-effective for patients with the most to gain and less effective for those with better preoperative health status.

Aged↗

Comparative measurement efficiency and sensitivity of five health status instruments for arthritis research.

Five health status instruments were administered in random order to 50 arthritis patients before and after total joint arthroplasty. Relative efficiency and sensitivity in measurement of change in pain, mobility and physical function, social role and social activity, and global health were assessed. The instruments had highly correlated scores, but had differences in certain dimensions. Inter-instrument differentials were larger for social and global outcomes than for pain or mobility. NO single instrument consistently outperformed the others. A method for determining relative efficiency is described.

Activities of Daily Living↗

Impact of diagnosis-related group-based reimbursement for treatment of rheumatic diseases in a teaching hospital.

The impact of Medicare's diagnosis-related group (DRG)-based reimbursement system was examined for care given to 734 rheumatic disease patients discharged from a teaching hospital during a 2-year period. The analysis accounted for length of stay "outliers" as defined by Medicare and distinguished costs from charges. Excluding outliers, DRG reimbursement would result in net revenues to the hospital of +1,126 per DRG 240 patient and $1,794 per DRG 241 patient. The difference between DRGs in cost per patient was significant, indicating that DRGs clearly identify 2 groups of rheumatic disease patients. After excluding outliers, the coefficients of variation in costs for DRGs 240 and 241 were 72% and 80%, respectively, which although high, were average for DRGs at our institution. Mean total charge per patient was different for groups defined by their primary rheumatologic diagnosis in DRG 240 but not DRG 241. For rheumatoid arthritis and systemic lupus erythematosus patients, the total charge per patient did not differ, but the types of services did. The cost of treating outliers would create an average loss per outlier of $18,400 and $16,500, respectively, in DRGs 240 and 241. Outliers accounted for 34.5% and 21.8% of the 2 DRGs' total costs, respectively, but only 6.4% and 3.6% of the total number of patients. Under current DRG reimbursement rates, the cost of care for rheumatology patients would be adequately reimbursed in our hospital: losses from outliers would be offset by net revenues from inliers as long as current Medicare adjustments for capital and medical education costs were continued.

Costs and Cost Analysis↗

Measuring function and health status in rheumatic disease clinical trials.

We have summarized the limitations of traditional outcome measures in rheumatology, reviewed the growing field of measures emphasizing the patient's perception of improvement, and provided guidelines for choosing a specific instrument for a clinical trial. Newer measures have measurement properties equal to or surpassing traditional measures, but no one ADL or quality-of-life instrument can be used to assess outcome in every situation as no one test can indicate success of a treatment in a chronic disease. An instrument needs to be judged by the following criteria: Is it metrically sound? Does it fit the socio-demographic characteristics of the target population? Does it measure the specific changes which are likely to be affected by the treatment? Will it capture or measure the expected changes?

Arthritis, Rheumatoid↗

Energy expenditure during ambulation with ortho crutches and axillary crutches.

Thirteen normal male college students were studied during unassisted ambulation and nonweight-bearing ambulation with Ortho crutches and axillary crutches to determine energy expenditure. Subjects walked at self-selected velocities. Energy expenditure was determined by analyzing expired air collected by a calorimeter. Heart rate was monitored by telemetry. During the first 2.5 minutes of walking, heart rate and energy expenditure were significantly greater for ambulation with axillary crutches than with Ortho crutches. After 11.5 minutes of walking, no difference in energy cost was found between crutch types; however, heart rate increased significantly (p less than .01) during ambulation with axillary crutches. Differences in energy cost and heart rate were attributed to increased upper extremity work performed when using axillary crutches. We concluded that during nonweight-bearing ambulation for short periods of time or over a short distance, the Ortho crutch is less taxing in terms of energy cost and heart rate demands.

Adult↗

Primary total hip or knee replacement: evaluation of patients.

Total joint replacement surgery has revolutionized the management of chronic arthritis. Careful patient selection, medical follow-up, patient education, and rehabilitation management produce the best results. The indications, contraindications, and results of total knee and hip replacement are reviewed.

Arthritis↗

Evaluation of outcomes in total joint arthroplasty for rheumatoid arthritis.

As the causes of most chronic diseases are multifactorial, so are their outcomes. The first two decades of joint arthroplasty witnessed rapid technologic advances and diffusion. Short-term outcomes measured by traditional clinical parameters show remarkable successes. Long-term results measured traditionally and including patient- and society-oriented outcomes, e.g., health status, cost, and satisfaction, need greater emphasis in the evaluation of surgical management of polyarticular disease. Long-term studies that use standardized outcome measurement are crucial in the future development of the technology and in the refinement of patient selection criteria to achieve optimal outcome. A larger view of the end-results can be measured reliably, but their interpretation and refinement need careful study.

Activities of Daily Living↗