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Biomedical subjects

W B Young

Publications and source records attributed to W B Young.

At least 55 records · Page 3Linked to original sources
PubMed2000

DNA methylation of helper virus increases genetic instability of retroviral vector producer cells.

Retroviral vector producer cells (VPC) have been considered genetically stable. A clonal cell population exhibiting a uniform vector integration pattern is used for sustained vector production. Here, we observed that the vector copy number is increased and varied in a population of established LTKOSN.2 VPC. Among five subclones of LTKOSN.2 VPC, the vector copy number ranged from 1 to approximately 29 copies per cell. A vector superinfection experiment and Northern blot analysis demonstrated that suppression of helper virus gene expression decreased Env-receptor interference and allowed increased superinfection. The titer production was tightly associated with helper virus gene expression and varied between 0 and 2.2 x 10(5) CFU/ml in these subclones. In one analyzed subclone, the number of integrated vectors increased from one copy per cell to nine copies per cell during a 31-day period. Vector titer was reduced from 1.5 x 10(5) CFU to an undetectable level. To understand the mechanism involved, helper virus and vectors were examined for DNA methylation status by methylation-sensitive restriction enzyme digestion. We demonstrated that DNA methylation of helper virus 5' long terminal repeat occurred in approximately 2% of the VPC population per day and correlated closely with inactivation of helper virus gene expression. In contrast, retroviral vectors did not exhibit significant methylation and maintained consistent transcription activity. Treatment with 5-azacytidine, a methylation inhibitor, partially reversed the helper virus DNA methylation and restored a portion of vector production. The preference for methylation of helper virus sequences over vector sequences may have important implications for host-virus interaction. Designing a helper virus to overcome cellular DNA methylation may therefore improve vector production. The maintenance of increased viral envelope-receptor interference might also prevent replication-competent retrovirus formation.

Cell Line↗
PubMed1999

Death by managed care--denial of hospitalization for headache.

A 47-year-old man with a severe headache disorder, taking meperidine injections 8 to 12 times a day and approximately 6 butalbital-containing tablets per day, was denied hospitalization for the management of headache and died while awaiting evaluation for detoxification by a psychiatric facility. The criteria for hospitalization and the implications of the denial of care by insurance companies are explored. The biases against the publication of such cases are reviewed.

Headache↗
PubMed1999

A comparison of drop jump training methods: effects on leg extensor strength qualities and jumping performance.

The purpose of this study was to determine the effects of two drop jump (DJ) training methods on the strength qualities of the leg extensors and vertical jumping performance. Thirty-five males were allocated to either a control group or one of two training groups, required to perform 72-90 DJ per week for 6 weeks: DJ for maximum rebound height (DJ-H) or DJ for maximum height and minimum ground contact time (DJ-H/t). The subjects were tested before and after the training on leg extensor function for maximum strength and speed-strength under concentric and stretch-shortening cycle muscular actions, and on vertical jumps from a standing position and a run-up. ANOVA with repeated measures showed that a 20% gain in reactive strength (RS) for the DJ-H/t group was significantly greater (p < 0.05) than the other groups, however, this did not transfer to vertical jumping performance. The DJ-H group did not achieve a significant training effect. It was concluded that DJ-H/t method was effective for the development of RS, but training with DJ-H was not intense and/or specific enough to stimulate gains in strength qualities of the leg extensors or jumping performance.

Adult↗
PubMed1998

Idiopathic intracranial hypertension without papilledema: a case-control study in a headache center.

OBJECTIVE: To compare the clinical features of patients with chronic daily headache (CDH) with idiopathic intracranial hypertension without papilledema (IIHWOP) to those with normal CSF pressure. METHODS: A case-control study was conducted at a tertiary headache center. Cases consisted of 25 consecutive patients (24 women, 1 man, 38 +/- 6 years) with IIHWOP diagnosed between June 1989 and June 1996. IIHWOP was diagnosed if pressure was 200 mm CSF on two occasions and there was no papilledema. Control subjects consisted of patients with refractory CDH who had normal CSF pressure on lumbar puncture performed between June 1992 and June 1996 (n = 60, 50 women, 10 men, 36 +/- 11 years). A structured telephone follow-up was done from July 1996 to March 1997. Comparisons made between the two groups included demographics and headache profiles, both at the initial evaluation and at follow-up. RESULTS: The initial headache characteristics did not differ between the two groups: most had transformed migraine with analgesic overuse. Significant predictors of IIHWOP included pulsatile tinnitus (odds ratio [OR] = 13.0) and obesity (OR = 4.4). Visual symptoms did not differ significantly. The prognosis of the two groups of patients was similar. CONCLUSIONS: Pulsatile tinnitus and obesity suggest possible IIHWOP in patients with CDH. Treatment of patients with increased intracranial pressure was not satisfactory.

Adult↗
PubMed1997

A novel herpesvirus amplicon system for in vivo gene delivery.

For gene therapy approaches to succeed, improved vector systems are needed that combine a large carrying capacity with high transduction efficiency in vivo. Towards this goal, we have developed a novel herpes simplex virus (HSV) amplicon vector, pHE, which contains an HSV-1 replication origin (ori S) and packaging sequence that permit vector replication and packaging into HSV-1 capsids. The vector also contains the Epstein-Barr virus (EBV) unique latent replication origin (ori P) sequence and a modified EBNA-1 gene to allow the vector to be maintained as an episome in transfected E5 helper cells. This system allows for efficient packaging of high-titer vector since the E5 cells are first selected for the presence of the pHE vector before helper virus infection. The infectious pHE vector has efficient transgene expression in a variety of human cell lines in vitro. Stereotactic injection of pHE vector supernatant into the rat brain resulted in high, localized reporter gene expression. Finally, the pHE vector could carry a stable 21 kb DNA payload into HSV virions. This pHE vector system should have a broad range of gene transfer applications.

Animals↗
PubMed1997

Paroxysmal headache caused by colloid cyst of the third ventricle: case report and review of the literature.

Colloid cysts of the third ventricle are benign tumors that may cause brief, severe headache and, rarely, death. We present a patient with frequent, episodic, brief, severe headaches of 2 weeks' duration who suddenly became obtunded. We reviewed the literature on the symptomatology of colloid cysts and conclude that any patient with less than a 1-year history suggestive of a third ventricular colloid cyst causing brief, severe headaches should be aggressively investigated.

Adult↗
PubMed1997

Droperidol treatment of status migrainosus and refractory migraine.

We conducted a pilot study of intravenous droperidol in 35 patients (32 women and 3 men; mean age 43 years) with status migrainosus (n = 25) or refractory migraine (n = 10) in an ambulatory infusion center. Headache was graded as severe in 21 patients and moderate in 14. An intravenous line was started and kept open. Droperidol (2.5 mg) was given intravenously every 30 minutes until either three doses were given or the patient was completely or almost headache-free prior to the next dose. Seven patients received one dose, 12 received two doses, and 16, three doses (mean 5.6 mg). Our success rate (headache-free or mild headache) was 88% (22 of 25) in patients with status migrainosus and 100% (10 of 10) in patients with refractory migraine. The average time to headache improvement was 40 minutes (n = 35), to mild headache--60 minutes (n = 32), and to headache-free--105 minutes (n = 28). Nausea, vomiting, and light and sound sensitivity resolved in all but 5 patients. Four patients had an asymptomatic systolic blood pressure drop > or = 20 mm Hg. Most patients were sedated (34 of 35). Five patients developed akathisia and 1 dystonia. At follow-up 24 hours after discharge, the recurrence rate (headache intensity from none or mild to moderate or severe) was 23% in status migrainosus and 10% in refractory migraine. Twenty-one patients were sedated, while 19 had extrapyramidal symptoms, mainly restlessness. Droperidol is effective and safe in treating status migrainosus or refractory migraine. Hypotension was uncommon. Patients should be warned of sedation and akathisia.

Adolescent↗
PubMed1997

Migraine treatment.

Migraine is a primary headache disorder characterized by recurring attacks of pain and associated symptoms. Migraine sufferers require a continuum of clinical care that depends on their disability and response to treatment. Treatment consists of: (1) prevention of attacks by avoidance of triggers; (2) the use of nonpharmacologic treatments; (3) treatment of the acute attack; and (4) long-term prophylactic therapy. Migraine is comorbid for affective disorders, epilepsy, stroke, and mitral valve prolapse. The therapy selected depends on the headache severity and frequency, the pattern of associated symptoms, comorbid illnesses, and the patient's treatment response profile. Acute treatment can be symptomatic or specific, using drugs such as dihydroergotamine (DHE) or sumatriptan. Preventive treatment can be episodic, subacute, or chronic. The major drug groups include beta-adrenergic blockers, anti-depressants, calcium channel blockers, serotonin antagonists, anticonvulsants, and nonsteroidal anti-inflammatory drugs (NSAIDs). These can be divided into two major categories and second-line choices.

Analgesics↗
PubMed1997

Incremental health insurance reform proposals to improve access.

This three-part series on health legislation describes the policy shift toward regulating the private healthcare system to ensure adequate consumer protection and access to health insurance. Still burning from the failed 1993-1994 healthcare reform effort, Congress and the White House are looking only for incremental policies necessary to reduce the federal deficit and protect the public while the private healthcare system continues to undergo major transformation. In previous articles, the author discussed Medicare, Medicaid, and other federal program revisions and consumer protection legislation aimed at unacceptable managed cure practices. This last article discusses incremental health insurance proposals aimed toward segments of the uninsured.

Child↗
PubMed1997

What influences patients' reports of three aspects of hospital services?

OBJECTIVES: Market forces make it essential to know what policies and actions influence patients' reports of hospital services. No studies have examined the role of patient characteristics, labor quality and staff characteristics, nonlabor resources, managerial practices, and employee attitudes within a single investigation. METHODS: The authors collected, simultaneously, data about labor, management and service processes, nonlabor resources, and employee attitudes on 117 nonintensive medical-surgical inpatient units in 17 hospitals selected from a pool of 69 institutions within a metropolitan area by a stratified random sample. Of the 2,595 patients who agreed to participate, 2,051 (79%) completed telephone interviews regarding their experiences with physical care, education, and pain management services within 26 days of hospital discharge. RESULTS: A significant amount of variation in patients' service reports was explained (adjusted R2 = 0.41 physical care, 0.35 pain management, 0.44 education). Although the predictors varied for each service report, patient characteristics, especially those related to personal resources, had a large explanatory role. A labor assignment pattern that could explain why earlier studies found labor quality and staff characteristics to have only a weak role in the prediction of patients' service reports was noted. CONCLUSIONS: The results related to patient characteristics may indicate opportunities to improve care by confronting service design strategies that erroneously rely on a homogeneous patient population. Measurement challenges identified by this study must be addressed to determine the role of labor quantity and staff characteristics.

Health Care Surveys↗
PubMed1997

Appropriate use of ergotamine tartrate and dihydroergotamine in the treatment of migraine: current perspectives.

Considerable uncertainty exists regarding the appropriate use and dose limitations for ergotamine tartrate (ET) and dihydroergotamine (DHE) for the treatment of migraine despite more than 50 years of clinical experience. The Quality Standards Subcommittee (QSS) of the American Academy of Neurology (AAN) appointed an advisory committee from experts in the Headache and Facial Pain Section. As their initial project, the committee elected to review the clinical literature on the appropriate use of these compounds in the treatment of migraine. Subsequently, clinical practice guidelines were formulated and recently published in Neurology. The Headache and Facial Plan Section and the QSS of the AAN were able to reach consensus on the basis of a thorough literature review and formulated practice parameters that describe and define the limits of ergot use, provide information on the oral and parenteral dosing of ET and DHE, and provide physicians with guidance to avoid ET overuse by patients. Because this project was completed prior to the availability of the intranasal (IN) formulation of DHE, intranasal DHE is not included in the practice parameter. Ergotamine tartrate and DHE were found to be safe and effective for the treatment of migraine as long as recommended dosages are not exceeded and high-risk patients such as those with uncontrolled hypertension, coronary or peripheral artery disease, thyrotoxicosis, or sepsis do not receive these compounds. In addition, the committee recommended restricting the use of ET in some instances because the overuse of ET has been associated with physical and psychological dependence resulting in predictable recurrent and/or rebound headaches, and subsequent severe withdrawal symptoms, including nausea, upon discontinuance of ET. None of these symptoms have been reported for DHE. These guidelines should help physicians provide optimal antimigraine therapy with these drugs.

Analgesics, Non-Narcotic↗
PubMed1996

Model for a nursing center: spanning boundaries.

The article provides an example of spanning organizational and professional boundaries to improve care in a medically underserved community through the development of a nursing center. Descriptions of the practice and organizational models demonstrate how each was tailored to the specific community. Using Andersen's behavioral model of families' use of health services and objectives for the year 2000, the impact on access to care and population outcomes are evaluated.

Adolescent↗
PubMed1996

How wide is the gap in defining quality care? Comparison of patient and nurse perceptions of important aspects of patient care.

OBJECTIVES: The authors determine the importance that patients, nurses, and nurse managers place on aspects of care and measure nurses' care values based on their perceptions of their patients and nurse manager care values and their desire to meet these care expectations. BACKGROUND: The literature has documented gaps in how nurses and patients define quality and value specific care aspects, but little is known about the situation in the current continuous quality improvement and patient-centered care environment, which emphasizes a customer focus. Misunderstanding patients' values and expectations may impede service improvement. Information about any existing gaps could help managers begin to devise patient satisfaction improvement strategies. METHOD: Two thousand fifty-one medical-surgical patients, 1264 staff members, and 97 nurse managers from 17 randomly selected hospitals participated in study activities related to selected aspects of patient care. Trained interviewers surveyed patients by telephone within 26 days of discharge using a pretested instrument. Staff members and managers completed a coordinated written tool. Descriptive and correlational statistics were used in individual and unit-level analyses. RESULTS: Staff members perceive correctly that patients value differently various aspects of care but do not agree with their managers on patients' value of aspects of care. Unit staff members' and managers' beliefs regarding patients' care values did not match those of their patients (-14 to 0.11 and -0.01 to 0.06 zero order correlations, respectively). CONCLUSIONS: A unit's errors in defining patients' values may be self-reinforcing. Strategies to reorient personnel, including adoption of those suggested by the diffusion of innovation literature, may help bridge the gap and change practice.

Attitude of Health Personnel↗