Gulliver's travels, assessment, reliability, and validity.
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Biomedical subjects
Publications and source records attributed to P S Smith.
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Most immunosuppressed individuals who develop progressive multifocal leukoencephalopathy (PML) have a rapid fatal outcome, whereas some become long-term survivors. We explored the impact of the cellular immune response against JC virus (JCV) on the clinical outcome of 7 HIV+ and 3 HIV- individuals with PML. Of the 4 HIV+/PML survivors, all had detectable cytotoxic T lymphocytes (CTL) specific for JCV T or VP 1 proteins compared to none of the 3 HIV+/PML progressors tested. Of the 3 HIV-/PML patients, 1 was recently diagnosed with PML and showed evidence of neurologic improvement without any treatment. This patient had CTL specific for the VP1 protein of JCV. The other 2 HIV-/PML survivors were stable 3-8 years after the diagnosis of PML. They did not have any detectable CTL against JCV. These findings suggest that JCV-specific immune response is associated with favorable outcome in HIV+ individuals with PML. The lack of detectable JCV-specific CTL in 2 HIV-/PML survivors might indicate a burnt-out disease without sufficient antigenic stimulation to maintain the cellular immune response. The detection of JCV-specific CTL in an HIV- patient recently diagnosed with PML, who was showing evidence of neurological improvement without any treatment, indicates that this finding may be used as a favorable prognostic marker of disease evolution in the clinical management of patients with PML. As the quest for an effective treatment of PML continues, JCV-specific cellular immune response deserves further attention because it appears to play a crucial role in the prevention of disease progression.
According to DiBenedetto, "Occupational health nurses enhance and maximize the health, safety, and productivity of the domestic and global work force" (1999b). This project clearly defined the multiple roles and activities provided by an occupational and environmental health nurse and assistant, supported by a part time contract occupational health nurse. A well defined estimate of the personnel costs for each of these roles is helpful both in demonstrating current value and in future strategic planning for this department. The model highlighted both successes and a business cost savings opportunity for integrated disability management. The AAOHN's Success Tools (1998) were invaluable in launching the development of this cost effectiveness model. The three methods were selected from several tools of varying complexities offered. Collecting available data to develop these metrics required internal consultation with finance, human resources, and risk management, as well as communication with external health, safety, and environmental providers in the community. Benchmarks, surveys, and performance indicators can be found readily in the literature and online. The primary motivation for occupational and environmental health nurses to develop cost effectiveness analyses is to demonstrate the value and worth of their programs and services. However, it can be equally important to identify which services are not cost effective so knowledge and skills may be used in ways that continue to provide value to employers (AAOHN, 1996). As evidence based health care challenges the occupational health community to demonstrate business rationale and financial return on investment, occupational and environmental health nurses must meet that challenge if they are to define their preferred future (DiBenedetto, 2000).
Gravity directs the early polar development in single cells of Ceratopteris richardii Brogn. It acts over a limited period of time during which it irreversibly determines the axis of the spore cell's development. A self-referencing calcium selective electrode was utilized to record the net movement of calcium across the cell membrane at different positions around the periphery of the spore during the period in which gravity orients the polarity of the spore. A movement of calcium into the cell along the bottom and out of the cell along the top was detected. This movement was specific, polarized, and strongest in a direction that opposed the vector of gravity. Treatment with nifedipine, a calcium-channel blocker, diminished the calcium current and caused the cell to lose its responsiveness to the orienting influence of gravity. Results shown suggest that calcium plays a crucial role in the ability of a single cell to respond to gravity and in the subsequent establishment of its polarity.
Circadian levels of melatonin were determined in the hepatic portal vein, cranial vena cava, and the lower aorta of ten juvenile pigs. Blood was sampled every hour for a total of 24 hr via temporary cannulas introduced into blood vessels under anesthesia. No peak levels of melatonin were found in the mid-scotophase, but hepatic portal concentrations peaked at 06.00 hr. Overall levels of melatonin were highest in the hepatic portal vein (range 35-65 pg/mL), followed by an artery (range 30-55 pg/mL) and the vena cava (range 25-35 pg/mL). Levels of melatonin exhibit strong variation between individual pigs, but generally the average levels from all three sources follow each other's time course. However, on occasion, melatonin levels in the hepatic portal vein varied independently from the levels in the vena cava. Large portal peaks were usually preceded by a feeding period and were associated with a subsequent period of sleep. The data indicate that: 1) there is no clear circadian rhythm of melatonin in the peripheral blood of pigs, 2) relatively little melatonin is metabolized during the first liver passage, 3) food intake may elevate melatonin levels in the hepatic portal vein, and 4) increased levels of melatonin originated in the gastrointestinal tract may induce sleep.
AIM: To determine the concurrent validity of three self-administered health-related quality of life (HRQOL) questionnaires when administered to patients with amyotrophic lateral sclerosis (ALS). BACKGROUND: ALS is the most common motor neuron disease among adults. As a rapidly progressive and fatal disease, ALS has devastating effects on the patient's relationships, functional capacity and mental health. HRQOL measures include information about patients' physical impairments, functional level, and psychosocial status. This study compares a tool designed for the ALS population, the Sickness Impact Profile ALS-19 (SIP/ALS19), and two tools designed to be used in any population, the Quality of Well-being Scale SA (QWB SA), and the SF-36 Health Survey (SF-36). Correlation of the scores would suggest that each tool is valid as a stand-alone measurement of quality of life for this patient population. METHODS: The SIP/ALS-19, the SF-36, and the QWB SA were self-administered to 19 subjects diagnosed with ALS. The scores for each test were ranked and analyzed for agreement using the Spearman rank correlation coefficient. RESULTS: The SIP/ALS-19 demonstrated moderate to good correlation with the QWB SA and fair correlation with the SF-36. The SF-36 had little to no correlation with the QWB SA. CONCLUSIONS: The study did not demonstrate significant correlation among the three quality of life measures. The SIP/ALS-19, SF-36, and QWB SA each have a different focus in measuring HRQOL. The healthcare practitioner should consider the patient's stage of disease, treatment goals, and type of interventions planned when selecting a HRQOL tool for the ALS patient.
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We report a 5-year-old girl with a large rapidly growing giant cell tumor of the mandible that recurred 2 months after the first surgical excision and 3 months after a second resection. An angiogenic protein, (bFGF), was abnormally elevated in her urine. The patient was treated with interferon alfa-2a for 1 year because this agent inhibits angiogenesis by suppressing bFGF overexpression in infantile hemangiomas and in other human tumors. During this time the bone tumor regressed and disappeared, the urinary bFGF fell to normal levels, and the mandible regenerated. She has remained tumor-free and has been off therapy for 3 years at this writing. This first successful use of interferon alfa-2a to treat a mandibular tumor in a child demonstrates: 1) low grade tumors that overexpress bFGF may respond to interferon alfa-2a, in a manner similar to life-threatening infantile hemangiomas; 2) antiangiogenic therapy, given without interruption for 1 year, was safe and effective in this patient; and 3) treatment may be continued for 1 year without the development of drug resistance.
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OBJECTIVE: To review the medical literature on management of end-stage renal disease (ESRD) and its complications in the pediatric patient. DATA SOURCES AND STUDY SELECTION: MEDLINE searches (1970-1997) of the English-language literature. Clinical trials and reviews of drug therapy management were included, and bibliographies were reviewed for relevant articles. DATA SYNTHESIS: Principles of renal replacement therapy in children have been expanded to include maintenance of fluid and electrolyte balance and to manage the complications of ESRD in children. Types of renal replacement and their complications are reviewed. Complications of ESRD are reviewed with emphasis on drug therapy management of anemia of chronic renal failure, growth retardation, and hypertension. A discussion of the use of vitamins and supplements to maintain bone and mineral homeostasis is provided, and specific recommendations for vaccination of children with ESRD are given. CONCLUSIONS: Children with end-stage renal failure present a unique challenge to the pharmacist. Renal replacement therapy for children with ESRD involves some form of dialysis and an intensive medication regimen. Complications must be treated with appropriate drug therapy. Drug therapy must be monitored closely for dosage adjustment, clinical response, drug interactions, and toxicity. Patients and families must receive continuous education and follow-up to encourage compliance. The pharmacist must work closely with the healthcare team to optimize drug therapy and improve patient education and compliance.
UNLABELLED: This activity is designed for healthcare providers making formulary decisions for managed care organizations. GOAL: To help clinicians determine whether managed care formularies meet the needs of pediatric patients. OBJECTIVES: 1. List general considerations for establishing a pediatric drug formulary. 2. Understand the importance of growth and development when selecting drug therapy for pediatric patients. 3. Discuss potential difficulties with administering medications during school hours. 4. Identify specific medications within the drug classes of antibiotics, asthma medications, endocrine, and gastrointestinal agents that should be available on a pediatric drug formulary.
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OBJECTIVE: To assess the incremental cost-effectiveness of prophylactic compared with episodic care in boys with severe hemophilia A. SETTING: Eleven U.S. hemophilia treatment centers. METHODS: Charge data from a randomly selected cohort of 70 boys receiving episodic infusions for bleeding events and from all 27 boys receiving infusions prophylactically were collected from documents obtained from the hemophilia treatment centers during a period of approximately 2 years. Published and public sources were used for conversion to cost, lifetime earnings, and earnings losses from disability. A model was constructed for a hypothetical patient from ages 3 to 50 years by means of three infusion scenarios. RESULTS: The cohort receiving prophylactic treatment had fewer bleeding events each year (median, 3 vs 31) but used more concentrate (3323 vs 1015 units/kg per year). Factor VIII concentrate accounted for more than 93% of the cost of both episodic and prophylactic care. Compared with episodic infusion, prophylaxis from ages 3 to 20 years costs $1100 per bleeding event prevented, in comparison with $1380 for prophylaxis from ages 3 to 50 years. The total cost of prophylactic care from ages 3 to 50 years would equal the current total cost of episodic care if the price of the concentrate were decreased by 50%. CONCLUSION: Prophylactic care markedly reduces the number of bleeding events and should prevent joint function impairment, but at substantial cost.
Melatonin concentrations were determined in serum and 10 segments of the gastrointestinal tract (GIT) of 48 pigs (100 kg weight). The animals were fasted for 30 hr and then sacrificed 0, 1, 2, 5, 10, and 20 hr after refeeding. Peak amount of gastric digesta (2,428 g) and ileum digesta (850 g) were observed 1 hr and 5 hr, after refeeding, respectively. Conversely, colon content reached a minimal weight (726 g) at 2 hr after refeeding. Serum levels of melatonin increased from 3.4 pg/ml to 15.5 pg/ml (peak 5 hr after refeeding). Melatonin levels in GIT tissues before refeeding varied from 23.8 pg/g (stomach-fundus) to 62.1 pg/g (rectum). Increasingly higher levels of melatonin were detected in the distal segments of the GIT. Higher melatonin levels after refeeding were observed in most GIT tissues except the rectum. In most tissues, peak melatonin values were detected 5 hr after refeeding. A significant change in weight of digesta across time (P < 0.05) was detected in the stomach, ileum, and cecum. Similar changes in melatonin levels across time were found in most tissues except the esophagus, stomach (cardia and pylorus), and rectum. Adjacent GIT tissues exhibited similar (P < 0.05) melatonin levels. The GIT melatonin levels correlated best with the variation of digesta weight in the ileum. In addition, the increase of serum melatonin levels correlated best with the increase of GIT melatonin levels in the distal part of the GIT. Our results suggest that melatonin produced in the ileum, cecum, and colon may contribute significantly to the short-term increase of serum melatonin levels observed after refeeding.
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The relationship of basal lamina, a form of specialised extracellular matrix which separates epithelial cells and other cell types from adjacent stroma, to the behaviour of malignant neoplasms of epithelial origin is not well understood. However, it is widely acknowledged that the properties of local invasion and metastasis of carcinomas are linked to extracellular matrix (including basal lamina) changes. In the present study, the distribution of the major basal lamina components, type IV collagen and laminin, in normal rat tongue mucosa and experimentally induced oral carcinomas was investigated using post-embedding immunogold techniques and electron microscopy. The expression of these components was also quantitatively analysed using morphometry and immunocytochemistry. Results indicated that type IV collagen and laminin were confined to the lamina densa of normal oral epithelial basal lamina, and that both components were also detected in the lamina densa of basal lamina associated with carcinomas, and in the extracellular matrix of tumours. Furthermore, laminin was detected within stromal fibroblasts in normal tissues and experimental carcinomas. Quantitative analysis indicated that expression of laminin was significantly increased in carcinomas. In contrast, type IV collagen expression was significantly decreased. The quantitative changes observed in the two basal lamina constituents may be related to the process of tumour invasion, reflecting altered metabolic activities of tumour and stromal cells. These observations may be of use in understanding the architectural characteristics of oral mucosa basal lamina and in assessing the malignant potential of epithelial dysplasias or "premalignant" lesions.
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Ten years after continence training, 14 severely and profoundly mentally handicapped individuals were found to have substantially maintained their improvements in bladder control. Completely independent self-initiated toileting had not been maintained, but the level of prompting to toilet was considerably less than before training. Those who had received intensive individual training fared much better than those who had received less intensive group training. Intensive individual training was found to be cost effective and resulted in very substantial savings in career time.