Biomedical subjects

Jennifer L Waller

Publications and source records attributed to Jennifer L Waller.

35 records · Page 2Linked to original sources

PubMed2004

Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats.

BACKGROUND: Minocycline, a semi-synthetic tetracycline antibiotic, is an effective neuroprotective agent in animal models of cerebral ischemia when given in high doses intraperitoneally. The aim of this study was to determine if minocycline was effective at reducing infarct size in a Temporary Middle Cerebral Artery Occlusion model (TMCAO) when given at lower intravenous (IV) doses that correspond to human clinical exposure regimens. METHODS: Rats underwent 90 minutes of TMCAO. Minocycline or saline placebo was administered IV starting at 4, 5, or 6 hours post TMCAO. Infarct volume and neurofunctional tests were carried out at 24 hr after TMCAO using 2,3,5-triphenyltetrazolium chloride (TTC) brain staining and Neurological Score evaluation. Pharmacokinetic studies and hemodynamic monitoring were performed on minocycline-treated rats. RESULTS: Minocycline at doses of 3 mg/kg and 10 mg/kg IV was effective at reducing infarct size when administered at 4 hours post TMCAO. At doses of 3 mg/kg, minocycline reduced infarct size by 42% while 10 mg/kg reduced infarct size by 56%. Minocycline at a dose of 10 mg/kg significantly reduced infarct size at 5 hours by 40% and the 3 mg/kg dose significantly reduced infarct size by 34%. With a 6 hour time window there was a non-significant trend in infarct reduction. There was a significant difference in neurological scores favoring minocycline in both the 3 mg/kg and 10 mg/kg doses at 4 hours and at the 10 mg/kg dose at 5 hours. Minocycline did not significantly affect hemodynamic and physiological variables. A 3 mg/kg IV dose of minocycline resulted in serum levels similar to that achieved in humans after a standard 200 mg dose. CONCLUSIONS: The neuroprotective action of minocycline at clinically suitable dosing regimens and at a therapeutic time window of at least 4-5 hours merits consideration of phase I trials in humans in view of developing this drug for treatment of stroke.

Animals↗

PubMed2004

Spouses of persons with dementia: their healthcare problems, utilization, and costs.

Spouses of persons with dementia (PWD) often experience poor health outcomes related to the experience of living with the afflicted spouse. Using the Anderson and Aday Healthcare Utilization Model, we conducted a retrospective review of an administrative database from a private healthcare insurer to compare health problems that precipitate utilization, patterns of utilization, and costs of care of spouses of PWD (n = 979) to those of spouses of persons without dementia (n = 979). Spouses of PWD were treated for more anxiety disorders (OR = 2.97; 95% CI = 1.63-5.44), falls (OR = 7.72; 95% CI = 2.73-21.84), rheumatologic diseases (OR = 2.5; 95% CI = 1.24-5.06), and diabetes with no complications (OR = 1.53; 95% CI = 1.06-2.22), but less pneumonia (OR =.55; 95%; CI =.35-.88) than comparison spouses. Spouses of PWD had a higher number of emergency room (ER) visits (p =.01). There were no differences in costs between the groups. The findings can be used to develop interventions for spouses of PWD.

Accidental Falls↗

PubMed2004

Autoimmunity in Alzheimer's disease: increased levels of circulating IgGs binding Abeta and RAGE peptides.

Plasma samples derived from 33 Alzheimer's disease (AD) and 42 control participants were subjected to several steps to purify specific anti-(amyloid)Abeta IgGs. Affinity-purified IgGs binding the peptide Abeta1-42, a neurotoxic sequence derived from the trans-membrane amyloid precursor protein, exhibited nearly four-fold higher titers in AD patients compared with their control non-AD cohort. Affinity-purified IgGs binding a fragment of the receptor for advanced glycation end products (RAGE) likewise were increased nearly three-fold in AD individuals. Abeta and RAGE IgG titers were negatively correlated with cognitive status, i.e. the more cognitively impaired individuals tended to exhibit higher IgG titers. Abeta IgG titers were negatively correlated with age in the control group, but not with the AD group. Levels of circulating AB- and RAGE-like proteins were not different between AD and control participants, nor was there a relationship between individual IgG titers and the respective Abeta- and RAGE-like proteins. Freshly prepared leukocyte preparations were subjected to flow cytometric analysis. AD individuals exhibited significantly increased populations of cells expressing binding sites for monoclonal antibodies directed against Abeta (5.5-fold), betaAPP (3.5-fold), and RAGE (2.6-fold) relative to the control group. These findings confirm the presence of circulating IgGs specifically directed at proteins implicated in immunological processes linked to AD. The close relationship between titers for Abeta and RAGE IgGs suggests the possibility that the antibodies are being produced in response to a common mechanism or protein complex (with the respective epitopes) linked to the disease.

Adult↗

PubMed2004

Mortality in patients with microvascular disease.

Patients with chest pain/ischemic cardiac disease and normal coronary arteriography are thought to have a benign prognosis despite diminished quality of life. Many patients with hypertension fall into this group, at least in the early stage of their disease. Whether abnormalities in coronary flow reserve in these patients are associated with increased morbidity and mortality is unknown. One hundred sixty-eight patients with chest pain/ischemic cardiac disease and normal coronary angiograms who underwent invasive measures of coronary flow reserve were followed longitudinally. Mortality and quality of life were ascertained by query of the national death index and telephone administration of standardized questionnaires. Patient follow-up occurred at a mean of 8.5 years. In the abnormal coronary flow reserve group, 12 deaths (20%) were documented in 60 patients compared with eight out of 108 patients (7%; p=0.016) with normal coronary flow reserve. Coronary flow reserve did not predict impairment in functional health status in long-term follow-up. Thus, invasive measures of coronary flow reserve in patients with chest pain/ischemic cardiac disease and normal coronary angiograms predicted increased mortality. Surviving patients with chest pain/ischemic cardiac disease and normal coronary angiograms have significant morbidity.

Blood Flow Velocity↗

PubMed2004

Single slice method for quantification of hemorrhagic transformation using direct ELISA.

An important area of experimental stroke research addresses the development of brain hemorrhage after cerebral ischemia. Investigations of hemorrhagic transformation, however, have been compromised by the absence of sensitive methods for quantification of hemorrhagic transformation. We have developed a direct ELISA method that is sensitive, reproducible and can be conducted on tissue treated with triphenyltetrazolium chloride, a stain commonly used for infarct size determination. We have also localized the slices containing the most hemoglobin to facilitate a single slice analysis. This allows two essential variables in experimental stroke research to be assessed on the same slice, leaving the rest of the brain available for other analysis.

Animals↗

PubMed2004

In vitro evaporative vs. convective water flux across human dentin before and after conditioning and placement of glass-ionomer cements.

PURPOSE: To assess the convective and evaporative fluid movement across glass-ionomer treated dentin. METHODS: Crown segments made from extracted human teeth, were divided into two groups of 14 teeth each. Each segment was cemented onto a plexiglass slab penetrated by a stainless steel tube, permitting filling of the pulp chamber with water. This set-up was attached to a device that measured fluid movement through the dentin in the crown segment. The experimental design involved repeated measurements of convective and evaporative fluid movements in each of the following conditions: smear layer-covered dentin, conditioned dentin, dentin after placement of one of two glass-ionomers (Fuji IX or Ketac-Molar), with and without a protective coating. The same water fluxes were remeasured after storage of the samples for 24 hours in distilled water. RESULTS: Statistical analysis of the results using ANOVA indicated a significant difference between the two measured water fluxes (P < 0.001). There was also a significant difference between the two materials (P < 0.001), with Ketac-Molar allowing higher permeability than Fuji IX. Conditioning the dentin surface with polyacrylic acid increased the convective water flux (P < 0.05) but did not change the evaporative water flux. Placement of the glass-ionomer material did not change the rate of spontaneous evaporation of water from the dentin, but the application of a coating agent reduced the evaporative water loss. These values were not significantly different when the specimens were stored for 24 hours.

Acrylic Resins↗

PubMed2004

A randomized study to decrease the use of potentially inappropriate medications among community-dwelling older adults in a southeastern managed care organization.

BACKGROUND: Despite progress in describing the problem of potentially inappropriate medication (PIM) use, there have been few prospective studies demonstrating that interventions with specific medication criteria can make a difference in decreasing the use of problematic drugs in older adults. OBJECTIVE: To design an intervention study to change physician behavior regarding PIM prescribing to older patients. STUDY DESIGN AND METHODS: A prospective randomized block design was used during an 18-month period from January 2001 to June 2002. The study population was primary care physicians (n = 355) in the Medicare + Choice product line of a southeastern managed care organization and their patients 65 years and older. There were 170 physicians in the treatment group and 185 in the control group. Physicians were assigned to the treatment or usual-care, groups using a randomization table, and each group included physicians who had and had not prescribed a PIM. RESULTS: Approximately 71% (84/118) of the physicians in the intervention group who prescribed a PIM completed and faxed back at least 1 potentially inappropriate medication form to the managed care organization. On 15.4% (260/1692) of the medication forms, physicians made some change regarding PIM use. CONCLUSIONS: Although many studies have addressed medication use among older adults, intervention studies aimed at influencing physician prescribing in this population are limited. This study describes a low-cost, replicable method to contact and educate physicians on drug therapy issues in older adults.

Academic Medical Centers↗

PubMed2003

Cytokine response to diabetic ketoacidosis and its treatment.

The objectives of this study were to monitor plasma cytokines as markers of cellular activation and as potential markers for the progression of the acute complications of diabetic ketoacidosis (DKA). Blood samples were obtained prior to, during and after treatment of severe DKA (pH < 7.2) in six children and adolescents. Plasma IL-10, IL-1beta, TNF-alpha, IL-6, IL-8 and IL-2 cytokine levels were assayed by ELISA at each of the time points. Prior to treatment, elevations of multiple cytokines were found, the highest being IL-10. Treatment of DKA resulted in a significant decrease of IL-10 at 6-8 h (p = 0.0062), and further increases in the inflammatory cytokines at 6-8 h and/or 24 h vs 120 h (baseline): IL-1beta (p =.0048); TNF-alpha (p =.0188) and IL-8 (p =.0048). This study strengthens the hypothesis that the metabolic crisis of DKA, and its treatment, have differential effects on cellular activation and cytokine release. The time frame for the increase in inflammatory cytokines correlates with the reported progression of subclinical brain edema, interstitial pulmonary edema and the development of clinical brain edema.

Adolescent↗

PubMed2002

Differential effects of haloperidol, risperidone, and clozapine exposure on cholinergic markers and spatial learning performance in rats.

Haloperidol (HAL), a potent typical antipsychotic, continues to be a frequently prescribed medication for behavioral disturbances associated particularly with schizophrenia despite well-documented adverse effects associated with its chronic use. Animal experiments have even indicated that HAL can damage cholinergic pathways and thus could be especially deleterious to those experiencing cognitive deficits. However, several recent clinical studies indicate that atypical antipsychotics may actually improve cognitive function in some patients, although this assertion requires further investigation. The purpose of this study was to compare the effects of prior chronic (45- or 90-day) oral exposure to HAL and the atypical antipsychotics risperidone (RISP) and clozapine (CLOZ) on cognitive performance and central cholinergic markers in rats. All analyses were done after 4 days of drug washout in order to minimize direct drug effects. Learning performance and choline acetyltransferase (ChAT) levels were assessed in a water maze task and with immunofluorescence staining, respectively. HAL significantly impaired learning performance after 90 but not after 45 days of treatment when compared to both vehicle controls and the atypical agents, while RISP slightly improved task performance. Both 45 and 90 days of previous HAL exposure reduced ChAT staining in several brain regions, including the cortex, caudate-putamen, and hippocampus. ChAT staining in the caudate-putamen and hippocampus was also decreased after 90 days of RISP exposure, raising the possibility of deleterious cognitive effects after exposure to this dosage for longer periods of time. The results suggest that antipsychotic drugs exert differential and temporally dependent effects on central cholinergic neurons and learning performance.

Animals↗

PubMed2002

Atypical neuroleptics stimulate neurogenesis in adult rat brain.

Schizophrenia has been treated effectively with atypical neuroleptics without serious side effects. We have shown previously that long-term treatment with atypical neuroleptics is correlated with an improvement of cognition in adult rats. We report here that atypical neuroleptics stimulate a 2- to 3-fold increase in newly divided cells in the subventricular zone in the rat and that some of these new cells in the subventricular zone and hippocampus also express a neuronal marker. We used bromodeoxyuridine (BrdU) to identify newly divided cells and confirmed the observation with antibody to a cell-cycle-specific, endogenous proliferating cell nuclear antigen (PCNA). Identification of BrdU-positive cells in the anterior subventricular zone (SVZa) particularly in rats treated with the atypical neuroleptics but not in those in the haloperidol-treated and control rats, suggests increased rostral migratory stream (RMS) cell traffic to replenish neurons in the olfactory bulb. Expression of a neuronal marker, NeuN, in BrdU-positive cells in rats treated with atypical neuroleptics, also suggests that these compounds may modulate in vivo differentiation of neuronal progenitor cells even within a day of BrdU injection. Our results indicate that atypical neuroleptics have a mechanism of action other than the previously proposed mechanisms, which might explain their role in improved cognition in animal and in schizophrenic patients. If substantiated by future studies, our findings may lead to an expanded use of atypical neuroleptics in other neurodegenerative diseases to stimulate neuronal replacement and repair.

Animals↗

PubMed2002

Angiotensin II activation of the JAK/STAT pathway in mesangial cells is altered by high glucose.

BACKGROUND: Both high glucose (HG) and angiotensin II (Ang II) causes glomerular mesangial cell (GMC) growth and increased synthesis of matrix proteins like collagen IV contributing to diabetic nephropathy. We have recently found that exposure of vascular smooth muscle cells to HG augments the Ang II activation of the growth promoting JAK/STAT pathway. We hypothesized that Ang II activation of the JAK/STAT pathway is altered by HG in GMC, and that this pathway might be linked to the Ang II-induced growth and overproduction of collagen IV in GMC in HG conditions. METHODS: GMC were cultured under normal glucose (NG; 5.5 mmol/L) and HG (25 mmol/L) for 48 hours and stimulated with Ang II (0.1 micromol/L) for various times. GMC lysate was then immunoprecipitated and/or immunoblotted with SHP-1, SHP-2 and phosphospecific JAK2 and STAT antibodies. The HG and Ang II induced growth and collagen IV synthesis studies were performed in GMC transfected with JAK2 antisense or JAK2 sense. GMC growth was monitored via [3H]-thymidine incorporation, and collagen IV synthesis via ELISA. RESULTS: We found that Ang II-induced JAK2, STAT1, STAT3, STAT5A/B and SHP-2 phosphorylations were enhanced by HG, whereas that of SHP-1 was reduced. Ang II-induced growth and collagen IV synthesis also were increased under HG conditions. Transfection of GMC with JAK2 antisense oligonucleotides blocked the Ang II-induced growth and collagen IV synthesis in both NG and HG conditions. CONCLUSION: These results provide evidence that activation of the JAK/STAT pathway by HG or/and Ang II may be of importance in the increased GMC cell growth and collagen IV synthesis that is seen in diabetic nephropathy.

Angiotensin II↗

PubMed2002

Comparison of 2 systems for clinical practice profiling in diabetic care: medical records versus claims and administrative data.

OBJECTIVES: To (1) describe the rate of glycosylated hemoglobin (HbA1c) testing and control in a primary care clinic at an academic medical center; (2) compare academic medical center and health maintenance organization (HMO) data for a subgroup of the same patients; and (3) discuss the challenges to accurate clinical practice profiling. STUDY DESIGN: Retrospective analysis of medical records and claims and administrative data. PATIENTS AND METHODS: We reviewed the medical records of 300 patients with diabetes mellitus from the Primary Care practice at an academic medical center (AMC). The HMO and AMC were in the southeastern United States. The study adhered to the National Committee for Quality Assurance's Health Plan Employer Data and Information Set 3.0 (1998) guidelines for collection of the numerator and denominator data. RESULTS: Overall, 275 (91.7%) of 300 patients underwent a documented HbA1c test (range, 77.8%-98.0% across the 5 Primary Care Associates clinic physicians). Of these 275 patients, 206 (74.9%; range, 52.4%-84.7%) were under "good control" (defined by the National Committee for Quality Assurance as an HbA1c level of < or = 9.5%). The mean (SD) HbA1c level was 8.45% (1.98%). Data from the HMO documented a rate of HbA1c testing of 36.3% (45/124) compared with 92.7% (115/124) based on case note review at the academic medical center. CONCLUSIONS: Current administrative and claims-based information systems have inherent weaknesses if used for performance measurement. Reliance solely on medical record review is time and cost prohibitive. To ensure complete reporting of mandated "quality measures" will necessitate the tracking of data across different healthcare systems.

Academic Medical Centers↗

PubMedDate not supplied

Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts.

BACKGROUND: Medication toxic effects and drug-related problems can have profound medical and safety consequences for older adults and economically affect the health care system. The purpose of this initiative was to revise and update the Beers criteria for potentially inappropriate medication use in adults 65 years and older in the United States. METHODS: This study used a modified Delphi method, a set of procedures and methods for formulating a group judgment for a subject matter in which precise information is lacking. The criteria reviewed covered 2 types of statements: (1) medications or medication classes that should generally be avoided in persons 65 years or older because they are either ineffective or they pose unnecessarily high risk for older persons and a safer alternative is available and (2) medications that should not be used in older persons known to have specific medical conditions. RESULTS: This study identified 48 individual medications or classes of medications to avoid in older adults and their potential concerns and 20 diseases/conditions and medications to be avoided in older adults with these conditions. Of these potentially inappropriate drugs, 66 were considered by the panel to have adverse outcomes of high severity. CONCLUSIONS: This study is an important update of previously established criteria that have been widely used and cited. The application of the Beers criteria and other tools for identifying potentially inappropriate medication use will continue to enable providers to plan interventions for decreasing both drug-related costs and overall costs and thus minimize drug-related problems.

Aged↗

PubMedDate not supplied

Variability of vaginal pH determination by patients and clinicians.

PURPOSE: Measurement of intravaginal pH provides a reasonable assessment of vaginal health but is fraught with the potential for several sampling errors. The purposes of the study were to determine the variability of self-sampled vaginal pH among women using an inexpensive swab-based pH test compared with a clinician-obtained specimen, and variability of vaginal pH within 3 regions of the normal vagina. METHODS: In this cross-sectional study, women obtained a vaginal specimen using a cotton-tip applicator, transferred it to pH paper, and interpreted the results. A clinician also blindly interpreted these tests. Thereafter, a clinician obtained 3 swab specimens from the proximal, middle, and distal vagina for pH testing. Results were compared using Wilcoxon signed rank test, interclass correlation coefficients, Bland-Altman plots, and mixed-model analysis of variance. RESULTS: Interclass correlation coefficients were moderately high comparing subjects with clinician for the swab-based pH test (0.74). Subjects' swab pH values (4.5) were significantly lower than clinicians' pH values (4.7, P = .0001). Intravaginal pH did not vary between the 3 anatomic locations. CONCLUSIONS: Self-sampled intravaginal pH interpretations vary slightly compared with clinician-obtained specimens. Because swab pH sampling does not detect an intravaginal pH gradient in normal women, self-sampling technique may vary considerably without affecting outcomes. Our findings support self-sampling for vaginal pH before using over-the-counter products for presumed vaginitis.

Adolescent↗

PubMedDate not supplied

Survey of behavior management teaching in predoctoral pediatric dentistry programs.

PURPOSE: The purpose of this study was to survey directors of predoctoral pediatric dentistry programs regarding the teaching of behavior management techniques. METHODS: Surveys were mailed to all 56 dental schools in the United States. Follow-up mailings were sent to nonrespondents. The survey contained items on program demographics and the program's teaching of communicative and pharmacologic techniques. Information was also obtained on informed consent and parental presence in the operatory. RESULTS: Surveys were returned by 48 schools. Two schools declined to respond because they had not yet accepted or graduated students. The final response rate was 89%. The mean (+/-SD) percentage of total didactic time devoted to behavior management was 12% (+/-6). Communicative techniques were taught as "acceptable" by 96% to 100% of programs, with the exception of the hand-over-mouth exercise (HOME). HOME was taught as "unacceptable" by 62% of programs. Active and passive immobilization of sedated and nonsedated children was taught as "acceptable" by 69% to 85% of programs. Sixty-seven percent to 98% of programs taught that pharmacologic techniques (nitrous oxide, conscious sedation, general anesthesia) are "acceptable." There was little evidence that the teaching of behavior management techniques had changed over the previous 5 years, nor that they were likely to change in the near future. Parental presence in the operatory was common for some procedures, particularly among younger children. CONCLUSIONS: Predoctoral programs teach as acceptable communicative and pharmacologic management techniques, with the exception of HOME. Predoctoral program directors report they are not likely to increase the amount of curricular time devoted to behavior management in the near future.

Anesthesia, Dental↗

PubMedDate not supplied

Survey of behavior management teaching in pediatric dentistry advanced education programs.

PURPOSE: The purpose of this study was to survey pediatric dentistry advanced education program directors regarding the teaching of behavior management techniques. METHODS: Surveys were mailed to all (65) advanced education programs in the United States. Follow-up mailings were sent to nonrespondents. The survey contained items on program demographics and the program's teaching of communicative and pharmacologic techniques. Information was also obtained on informed consent and parental presence in the operatory. RESULTS: Surveys were returned by 54 programs. Two programs declined to respond because they had not yet accepted or certified residents. The final response rate was 86%. The mean percentage (+/- SD) of total didactic time devoted to behavior management was 13% (+/-9.5). Communicative techniques were taught as "acceptable" by 98% of programs, with the exception of the hand-over-mouth exercise (HOME), which was taught as "unacceptable" by 54% of programs. Active and passive immobilization of sedated and nonsedated children was taught as "acceptable" by 76% to 98% of programs. All programs taught that pharmacologic techniques (nitrous oxide, conscious sedation, general anesthesia) are "acceptable." There was little evidence that the teaching of behavior management techniques had changed over the previous 5 years, nor that it is likely to change in the near future. Parental presence in the operatory was common for some procedures, particularly among younger children. CONCLUSIONS: Most programs do not teach HOME as an acceptable behavior management technique. The amount of curricular time devoted to behavior management is not likely to change appreciably in the near future.

Anesthesia, Dental↗

PubMedDate not supplied

A survey of members of the American Academy of Pediatric Dentistry on their use of behavior management techniques.

PURPOSE: The objective of this study was to survey members of the American Academy of Pediatric Dentistry (AAPD) regarding their use of behavior management techniques. METHODS: Surveys were mailed to 4,180 members, with a follow-up mailing to nonrespondents 2 months later. The survey contained items on demographic variables and use (current, past, and future) of communicative and pharmacologic techniques. Information was also obtained on informed consent, parental presence in the operatory, and parenting styles. RESULTS: Survey response was 66%. Communicative techniques are widely used, with the exception of the hand-over-mouth exercise (HOME). Immobilization for sedated and nonsedated children and pharmacologic techniques are used by a majority or near majority of respondents. Little change was reported in technique use over time, except that 50% of respondents indicated they use HOME less now than 5 years ago, and 24% plan to use it less over the next 2 to 3 years. Parental presence in the operatory appeared to be a common practice for some procedures and for children with special health care needs. The majority of respondents believed that parenting styles had changed in ways that adversely impacted children's behavior in the dental setting. CONCLUSIONS: Most practitioners have not changed their use of behavior management techniques in recent years, nor do they plan to change their use of them in the near future. HOME was the exception to these trends.

Adult↗