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Biomedical subjects

L Wheeler

Publications and source records attributed to L Wheeler.

At least 19 recordsLinked to original sources

Localization of the gene for familial primary pulmonary hypertension to chromosome 2q31-32.

Primary pulmonary hypertension (PPH), an often fatal disease, is characterized by elevated pulmonary artery pressures in the absence of a secondary cause. Endovascular occlusion in the smallest pulmonary arteries occurs by proliferation of cells and matrix, with thrombus and vasospasm. Diagnosis is often delayed because the initial symptoms of fatigue and dyspnea on exertion are nonspecific and definitive diagnosis requires invasive procedures. The average life expectancy after diagnosis is two to three years with death usually due to progressive right heart failure. The aetiology of the disease is unknown. Although most cases appear to be sporadic, approximately 6% of cases recorded in the NIH Primary Pulmonary Hypertension Registry are inherited in an autosomal dominant manner with reduced penetrance. Following a genome-wide search using a set of highly polymorphic short tandem repeat (STR) markers and 19 affected individuals from six families, initial evidence for linkage was obtained with two chromosome 2q markers. We subsequently genotyped patients and all available family members for 19 additional markers spanning approximately 40 centiMorgans (cM) on the long arm of chromosome 2. We obtained a maximum two-point lod score of 6.97 at theta = 0 with the marker D2S389; multipoint linkage analysis yielded a maximum lod score of 7.86 with the marker D2S311. Haplotype analysis established a minimum candidate interval of approximately 25 cM.

Centromere

A movement-based approach to language development in children who are deaf-blind.

A movement-based approach to the development of language in children with deaf-blindness includes utilization of the four coactive movement phases: resonance, coactive movement, nonrepresentation reference, and deferred imitation. Such an approach stresses the use of structure in the environment as well as the use of a hierarchy of media cues. These cues range from concrete to symbolic in their characteristics and assist children in learning more complex concepts. A movement based approach uses the salient features of individuals or objects to develop an understanding of the person or object. Such features initially are used to stimulate use of language concerning objects or individuals in the immediate environment, and later to refer to persons or concepts in a more abstract fashion.

Blindness

Kaiser Permanente Medical Center's pilot Tele-Home Health Project.

This is an interim report of a Kaiser Home Health Department study of the use of telemedicine technology in the home care setting. We present our study design and some early findings from the first six months of the project. Preliminary findings indicate the technology is dependable, and that average telehealth video visits are cost-effective and are about 60% shorter (18 minutes vs. 45 minutes) than on-site visits, with no decrease in patient satisfaction. The study will be completed in September of 1997. This study was initiated in 1996 to explore improving access to health services while maintaining quality of care, and to demonstrate the cost effectiveness of remote consultation technology in the home health setting. The the study, which began in May 1996, employs a randomized design approved by the Institutional Review Board and will be completed in approximately one year. This project was titled Tele-Home Health to acknowledge that a multi-disciplinary team would be composed mainly of nurse case managers, but would also include physical therapists, speech therapists, occupational therapists, home health aides, licensed

Aged

Adrenergic and imidazoline receptor-mediated responses to UK-14,304-18 (brimonidine) in rabbits and monkeys. A species difference.

Brimonidine is a relatively selective alpha-2 adrenoceptor agonist that is being developed for the treatment of glaucoma. Because brimonidine is chemically related to clonidine and has affinity for the nonadrenergic imidazoline receptor, its ocular effects may be unrelated to alpha-2 receptor activation. The objective of this study was to determine the pharmacology of the intraocular pressure (IOP) response to brimonidine in rabbits and monkeys and the side effects (miosis, cardiovascular depression) in monkeys. Conscious albino rabbits and cynomolgus monkeys were pretreated topically with the following receptor antagonists: rauwolscine (alpha-2), idazoxan (alpha-2, imidazoline), SKF 105854 (vascular postjunctional alpha-2), and prazosin (alpha-1). Intraocular pressure, pupil size, or blood pressure/heart rate was monitored noninvasively for 6 hours following dosing. Binding experiments were performed using [3H]brimonidine in membrane preparations from rabbit iris/ciliary body and from monkey cerebral cortex and brain stem. In rabbits, the ocular hypotensive response to brimonidine was unilateral and was inhibited by rauwolscine > idazoxan >> SKF 105854 = prazosin; this ranked order of potency correlated with displacement of [3H]brimonidine in the rabbit iris/ciliary body. In monkeys, brimonidine decreased IOP bilaterally and suppressed cardiovascular function suggesting a CNS site of action. Intraocular pressure and cardiovascular responses to brimonidine were inhibited by idazoxan >> rauwolscine > SKF 105854 = prazosin; a similar profile was obtained for displacement of [3H]brimonidine in monkey brain tissue. Both rauwolscine and idazoxan inhibited the miotic response to brimonidine in monkeys. Taken together, these results indicate that brimonidine stimulates an ocular alpha-2 adrenoceptor to decrease IOP in the rabbit and a CNS imidazoline receptor to decrease IOP, blood pressure, and heart rate in the cynomolgus monkey. The miotic response in the monkey is mediated by an alpha-2 adrenoceptor. The alpha-1 and vascular postjunctional alpha-2 adrenoceptors do not appear to play a role in mediating these responses.

Adrenergic alpha-2 Receptor Agonists

Participation in transvaginal ovarian cancer screening: compliance, correlation factors, and costs.

The objective was to identify factors influencing participation in screening for ovarian cancer using transvaginal sonography in the free experimental program at the University of Kentucky over its 6+ year history. Database records for screenings, performed from 1987 to June 1994, were utilized. Computer sorts, 1990 census information as predictors, and stepwise multiple regression analysis were employed. Participation in the model ovarian screening program took 3-4 years to approach > 300 screens/month, with repeat screenings exceeding new subject participation in this time period. A number of participants traveled > 200 miles for screening on both initial and repeat encounters. Analysis of distance to the screening site, median family income, county physician population, and education levels indicated that distance and then education correlated best with participation. Unit screening cost shrank from $45 to under $25 when maximal participation was achieved. Distance and education correlated with participation. Expenses compare favorably with diagnostic procedures for other diseases.

Adult

Clean intermittent catheterization: safe, cost-effective bladder management for male residents of VA nursing homes.

OBJECTIVES: To compare the safety and cost of clean versus sterile intermittent bladder catheterization in male nursing home residents. To provide evidence to support the hypothesis that intermittent catheterization is a valid, alternative method of bladder management in male residents of long-term care in whom urinary retention is a documented problem. DESIGN: Randomized clinical trial. SETTING: Three long-term care sites having predominantly male populations. PARTICIPANTS: Eighty male veterans, residents of three long-term care facilities, ranging in age from 36 to 96 years with a mean age of 72. INTERVENTIONS: Standardized procedures for clean and sterile intermittent catheterization (IC) were implemented by staff nurses at each site. Patients were randomized into clean and sterile IC groups. Nursing time and catheterization equipment usage were recorded using bar code readers. Clinical data were collected from the medical chart. Treatment of urinary tract infection was prescribed by the medical personnel responsible for each individual resident. MEASUREMENTS: We compared the number of treatment episodes for symptomatic bacteriuria between groups randomized to receive either clean or sterile intermittent catheterization. Laboratory analysis of blood and urine was done on predetermined days. Control variables were research site and patient history of urinary tract infection within the last 6 months. A cost comparison of nursing time and equipment usage for the two catheterization techniques was also performed. RESULTS: No significant differences were found between clean and sterile groups with regard to number of treatment episodes, time to first infection, type of organism cultured, or cost of antibiotic treatment. The cost of sterile technique was considerably higher both in terms of nursing time and supplies. CONCLUSIONS: Findings from this study demonstrate that clean technique intermittent catheterization is a safe and cost-effective bladder management technique with male, nursing home residents, despite the frailty of this high risk population. An annual savings of approximately $1460 per patient in nursing time and catheterization supplies could be anticipated if a patient were catheterized an average of four times per day substituting clean IC technique for sterile IC technique.

Adult

Specific associations of T4 bacteriophage proteins with immobilized deoxycytidylate hydroxymethylase.

Is the enzymatic machinery for DNA precursor biosynthesis linked to the DNA replication apparatus? To identify intermolecular associations among deoxyribonucleotide biosynthetic enzymes and to ask whether these enzymes are linked to replication proteins, we analyzed radiolabeled T4 bacteriophage proteins that bind specifically to a column of immobilized T4 deoxycytidylate hydroxymethylase. More than a dozen T4 proteins and a few Escherichia coli proteins are adsorbed specifically by this column. Several of the T4 proteins were identified by two-dimensional gel electrophoresis and radioautography. These include five enzymes involved in DNA precursor biosynthesis, dCMP hydroxymethylase, thymidylate synthase, dihydrofolate reductase, dCTPase-dUTPase, and ribonucleotide reductase large and small subunits, plus several proteins of DNA metabolism and replication. Analysis of extracts of cells infected with phage amber mutants defective in specific proteins suggested a specific association involving thymidylate synthase and the gene 32 single-strand DNA-binding protein.

Autoradiography

Murine model of cutaneous infection with gram-positive cocci.

Staphylococcus aureus has remained an important cause of nosocomial wound infections, but standardized or reproducible systems for analyzing cutaneous infections caused by S. aureus do not exist. A variety of foreign materials, variable inocula, and skin traumas have been used to promote infection. To minimize these variables and ensure reproducibility, we chose a model using subcutaneous injections of a fixed quantity of dextran microbeads (Cytodex) as the foreign material added to standardized broth suspensions of S. aureus. Suspensions (0.2 ml) injected into an outbred strain of immunocompetent hairless mice generated reproducible, measurable lesions. With S. aureus Smith Diffuse, fluctuant, erythematous lesions with a peak diameter of 15 mm were observed; these lesions yielded purulent material containing gram-positive cocci and neutrophils and yielded growth of S. aureus on culture. Lesion size was proportional to the bacterial inoculum size. Histologic examination of excised lesions revealed typical abscesses. A second strain of S. aureus (SLC3) produced dermonecrosis instead of abscesses at an inoculum size of 10(7) CFU. Control injections with a sterile Cytodex suspension regularly produced nondraining, nonerythematous nodules with maximum diameters of less than or equal to 5 mm. Streptococcus pyogenes produced late-onset necrotic lesions and abscesses. Using a foreign substance, this model generates easily observed and reproducible cutaneous infection with S. aureus and streptococci that can potentially discriminate between inter- and intrastrain differences. Such a model could be used to test the pathogenicity of isogeneic strains of these bacterial species and to evaluate the efficacy of antimicrobial agents.

Analysis of Variance

Effect of first-grade classroom environment on shy behavior, aggressive behavior, and concentration problems.

Investigates the effect of the first-grade classroom environment on the shy behavior, aggressive behavior, and concentration problems of 609 children in 19 East Baltimore public schools. First-grade classroom environment was assessed in terms of dominant pattern of classroom achievement and behavior. Structured teacher ratings assessed child shy behavior, aggressive behavior, and concentration problems at the end of first grade. Children in low-achieving classroom environments had significantly higher teacher ratings of shy behavior and aggressive behavior than children in mixed-achieving or high-achieving environments, even after controlling for potentially confounding child characteristics and classroom behavior environment effects. Analyses controlling for child characteristics and classroom achievement environment effects indicated that children in poor-behaving classroom environments also had significantly higher teacher ratings of shy behavior than children who were not in poor-behaving environments. Subgroup analyses indicated that repeaters in mixed-achieving environments had significantly higher levels of shy behavior compared with nonrepeaters, and repeaters in poor-behaving environments had significantly higher levels of aggressive behavior compared with nonrepeaters. Implications for prevention research are discussed.

Achievement

Experience with colposcopy in a family practice center.

The experience of a family practice center that performed colposcopy for one year was reviewed to provide insight into the appropriateness of this procedure to a family practice clinic. Almost three thousand Papanicolaou smears were performed, which prompted 97 colposcopy clinic appointments involving 68 patients. Dysplastic Pap smears accounted for 1.82% of the total. Atypical Pap smears occurred in 3.91% of the tests, and 16.1% of a sample of these demonstrated dysplasia. Controversy concerning the atypical Pap smear is discussed. The colposcopy service was convenient for the patients and was at least revenue neutral while providing a new professional opportunity for selected family practitioners. A referral base of at least 1,000 Pap smears might justify a colposcopy program, depending on referral strategies.

Ambulatory Care

The role of arachidonic acid metabolism in IL-3-induced proliferation.

The role of arachidonic acid metabolites as second messengers in the IL-3-induced activation of DA-1 cells was examined. By using inhibitors of either the cyclooxygenase (CO) or lipoxygenase (LPO) pathways, we determined that neither prostaglandins nor leukotrienes were involved in signal transduction, since aspirin, indomethacin, meclofenamic acid, and nordihydroguaiaretic acid (NDGA) failed to inhibit the proliferation response of DA-1 cells to IL-3. Furthermore, two combination CO/LPO inhibitors, benoxaprofen and BW755c, failed to inhibit DA-1 proliferation. A new CO/LPO compound examined, SK&F 86002, did inhibit proliferation (IC50 = 30 microM +/- 14, N = 11), leading us to conclude this drug has other actions besides CO/LPO inhibition. Finally, direct measurement of 3H-arachidonic acid uptake by DA-1 cells failed to show a difference in the amount of 3H-arachidonic acid incorporated in the presence of limiting or saturating amounts of IL-3. We conclude from these data that arachidonic acid metabolites are not involved in transmembrane signalling by IL-3 in DA-1 cells.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz

Inhibition of phosphoinositide-specific phospholipase C by manoalide.

Manoalide is a novel sesterterpenoid which has previously been shown to be a potent inhibitor of venom phospholipases A2. To determine whether manoalide inhibited other phospholipases, the sensitivity of phosphoinsitide-specific phospholipase C (PI-PLC) to inactivation by manoalide was examined using crude cytosolic PI-PLC and a PI-PLC purified to homogeneity from guinea pig uterus cytosol (PI-PLC I). Manoalide inhibited both cytosolic and purified PI-PLC I in a concentration-dependent fashion, exhibiting an IC50 of 3-6 microM. Inactivation of PI-PLC I was calcium- and pH-dependent, with greater inactivation occurring at alkaline pH. Manoalide inhibited hydrolysis of all three phosphoinositides by purified PI-PLC I. The substrate kinetics of PI-PLC I suggest that manoalide does not inhibit purified PI-PLC I by simple competitive or noncompetitive inhibition. Enzyme activity was not recovered after dialysis of manoalide-treated PI-PLC I, indicating that inactivation of PI-PLC I was irreversible. To determine whether manoalide inhibited PI-PLC in cells, the effects of manoalide on norepinephrine (NE)-stimulated phosphoinositide hydrolysis and calcium mobilization were investigated in a smooth muscle-like cell line, DDT1MF-2. Manoalide inhibited NE-induced inositol 1,4,5-trisphosphate and inositol 1-phosphate formation in a concentration-dependent manner. The IC50 for inhibition of inositol 1-phosphate formation was 1.5 microM. Manoalide also inhibited NE-induced calcium transients in DDT1MF-2 cells, exhibiting an IC50 of 2 microM. These data suggest that inhibition of PI-PLC may account, in part, for the anti-inflammatory actions of manoalide.

Animals

Extracellular calcium alters the effects of retinoic acid on DNA synthesis in cultured murine keratinocytes.

The rate of proliferation of epidermal keratinocytes was manipulated by growing the cells in medium containing high or low concentrations of calcium. Keratinocytes cultured in high extracellular Ca++ (1.4 mM and 2.8 mM) proliferated twice as fast as those grown in low Ca++ medium (0.09 mM) as measured by incorporation of [3H]thymidine into DNA. Exposure of high calcium keratinocytes to all-trans retinoic acid for 4 days caused a dose-related inhibition of DNA synthesis with an IC50 of about 10 microM. In contrast, incubating low calcium keratinocytes with all-trans retinoic acid caused a dose-related stimulation of DNA synthesis with maximum increase of 278% over control at 10 microM. This increase was accompanied by increases in culture confluency with maximum increase of 109% in cell number over control at 10 microM. These results are of importance since they suggest Ca++ may influence the effect of retinoids on keratinocytes.

Animals

Back school and chiropractic practice.

The back school as a method for teaching back pain prevention and self-care is discussed. Methods of developing and utilizing back schools are examined, and a review of research investigating the use of back school is presented. Future trends in back school are discussed. It is concluded that back schools can play an important part in the chiropractic office.

Back Pain

On specificity in the impact of social participation on physical and psychological health.

Although it has been suggested that social participation is likely to be beneficial for health and well-being, there is little research demonstrating specifically which aspects of socializing may be responsible. This study distinguishes specific components of social interaction and health and examines differential relationships among them. Three distinct categories of social participation variables were posited: quality, quantity, and social traits. If was hypothesized that health problems would be more frequent among persons with poor quality interaction. The only exception to this prediction was that illnesses that are socially communicated were expected to be more prevalent among persons with a greater quantity of social participation, regardless of quality. Results confirmed these predictions for females. For males, the pattern of results was more complex, in that masculinity and femininity influenced the manner in which symptoms were expressed. These results supported the notion that social relations have a specific impact on health, and that if research is to provide useful information for intervention, we must learn more about which specific aspects of social participation are beneficial as well as how this occurs.

Adaptation, Psychological

Loneliness, social interaction, and sex roles.

Forty-three male and 53 female college seniors maintained the Rochester Interaction Record for 2 weeks, providing information about every social interaction of 10 minutes or more. Subjects then completed the revised UCLA (University of California, Los Angeles) Loneliness Scale and the Personal Attributes Questionnaire, measuring sex-role orientation. For both sexes, loneliness was negatively related to the amount of time spent with females and to the meaningfulness of interaction with males and females. However, meaningfulness with males was more important than meaningfulness with females. Femininity was negatively related to loneliness for both sexes and partially mediated the above relationships. There were sex differences, however, in the extent to which variables overlapped in predicting loneliness. For example, a large group of nonlonely males was characterized both by having meaningful relationships with males and by spending time with females, whereas a second group of nonlonely males was characterized simply by having meaningful relationships with males. The largest group of nonlonely females was characterized simply by having meaningful relationships with males, but another sizable group was characterized simply by spending time with females. Females doing both accounted for very little of the variance.

Adult