Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 44
Filter
1.
J Perinatol ; 35(5): 353-6, 2015 May.
Article in English | MEDLINE | ID: mdl-25521560

ABSTRACT

OBJECTIVE: To determine whether Medicaid status influenced the effect of a quality improvement effort. STUDY DESIGN: Using a data set consisting of the 2006 to 2010 vital statistics data linked with Medicaid status data, we identified non-medically indicated inductions between 36 0/7 and 38 6/7 weeks gestational age and compared rates of non-medically indicated inductions between women with Medicaid and all other payers. We also compared these rates in hospitals that did and did not participate in the Ohio Perinatal Quality Collaborative (OPQC). RESULTS: A total of 232 935 births with gestational ages between 36 0/7 and 38 6/7 weeks were included in this study. In the sample, 32 371 births (13.9%) were non-medically indicated inductions. Overall, rates of non-medically indicated deliveries for all insurance types dropped over the course of the initiative. Interestingly, in OPQC participating hospitals, the Medicaid mothers' rates of non-medically indicated inductions prior to 39 weeks were well below rates for other insurance types prior to the initiative. By the end of the initiative, rates for all insurance types had dropped significantly but non-medically indicated inductions<39 weeks rates dropped more dramatically in the non-Medicaid mothers, resulting in higher rates for Medicaid than for non-Medicaid mothers. CONCLUSIONS: Non-medically indicated deliveries decreased for women irrespective of Medicaid enrollment status. However, non-medically indicated delivery rates did not drop as sharply for women enrolled in Medicaid.


Subject(s)
Delivery, Obstetric/trends , Labor, Induced/statistics & numerical data , Medicaid , Adult , Female , Gestational Age , Humans , Infant, Newborn , Ohio , Pregnancy , United States , Young Adult
2.
Epilepsy Behav ; 34: 73-6, 2014 May.
Article in English | MEDLINE | ID: mdl-24726950

ABSTRACT

We examined self-reported complementary and alternative medicine (CAM) use among a largely indigent population with epilepsy. Overall CAM use was 70%, with the most frequently reported complementary and alternative medicines (CAMs) being medical marijuana (33%), prayer/spirituality (31%), meditation (19%), vitamins (19%), and stress management (16%). Forty-four percent of patients reported improved seizure control with CAMs. Stress management accounted for perceived seizure reduction in 74%, followed by marijuana (54%), prayer (49%), and yoga (42%). Among the most commonly used and helpful CAMs, stress management was not associated with specific demographic or clinical variables; marijuana use was significantly associated with lower age (users=35.2±10 years vs. nonusers=41.6±12; p<0.01) and lower income (under $15,000 40% use vs. 14% over $15,000; p<0.05); and prayer was significantly associated with female gender (male=21% vs. female=45%; p<0.01) and Black ethnicity (Black=55% vs. Hispanic=30% vs. White=23%; p<0.05). Taken together, our study was notable for the high rate of CAM utilization in a largely indigent population, with high rates of perceived efficacy among several CAM modalities.


Subject(s)
Complementary Therapies/methods , Epilepsy/therapy , Hospitals, County , Patient Acceptance of Health Care , Adaptation, Psychological , Adult , Epilepsy/drug therapy , Epilepsy/psychology , Ethnicity , Female , Humans , Male , Medical Marijuana/therapeutic use , Middle Aged , Sex Factors , Spirituality , Surveys and Questionnaires , Vitamins/therapeutic use , Yoga
3.
Biomed Opt Express ; 3(8): 1947-54, 2012 Aug 01.
Article in English | MEDLINE | ID: mdl-22876357

ABSTRACT

Transbronchial needle aspiration (TBNA) is a procedure routinely performed to diagnose peripheral pulmonary lesions. However, TBNA is associated with a low diagnostic yield due to inappropriate needle placement. We have developed a flexible transbronchial optical frequency domain imaging (TB-OFDI) catheter that functions as a "smart needle" to confirm the needle placement within the target lesion prior to biopsy. The TB-OFDI smart needle consists of a flexible and removable OFDI catheter (430 µm dia.) that operates within a standard 21-gauge TBNA needle. The OFDI imaging core is based on an angle polished ball lens design with a working distance of 160 µm from the catheter sheath and a spot size of 25 µm. To demonstrate the potential of the TB-OFDI smart needle for transbronchial imaging, an inflated excised swine lung was imaged through a standard bronchoscope. Cross-sectional and longitudinal OFDI results reveal the detailed network of alveoli in the lung parenchyma suggesting that the TB-OFDI smart needle may be a useful tool for guiding biopsy acquisition to increase the diagnostic yield.

4.
Biomaterials ; 20(23-24): 2245-56, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10614931

ABSTRACT

The effect of polymer chemistry on adhesion, proliferation, and morphology of human articular cartilage (HAC) chondrocytes was evaluated on synthetic degradable polymer films and tissue culture polystyrene (TCPS) as a control. Two-dimensional surfaces of poly(glycolide) (PGA), poly(L-lactide) (L-PLA), poly(D,L-lactide) (D,L-PLA), 85:15 poly(D,L-lactide-co-glycolide) (D,L-PLGA), poly(epsilon-caprolactone) (PCL), 90:10 (D,L-lactide-co-caprolactone) (D,L-PLCL), 9:91 D,L-PLCL, 40:60 L-PLCL, 67:33 poly(glycolide-co-trimethylene carbonate) (PGTMC), and poly(dioxanone) (PDO) were made by spin-casting into uniform thin films. Adhesion kinetics were studied using TCPS and PCL films and revealed that the rate of chondrocyte adhesion began to level off after 6 h. Degree of HAC chondrocyte adhesion was studied on all the substrates after 8 h, and ranged from 47 to 145% of the attachment found on TCPS. The greatest number of chondrocytes attached to PGA and 67:33 PGTMC polymer films, and attachment to PCL and L-PLA films was statistically lower than that found on PGA (p < 0.05). There was no correlation between amount of chondrocyte attachment to the substrates and the substrates' water contact angle. Chondrocytes proliferated equally well on all the substrates resulting in equivalent cell numbers on all the substrates at both day 4 and day 7 of the culture. However, these total cell numbers were reached as a result of a 88- and 42-fold expansion on PDO and PLA, respectively, which was significantly higher than the 11-fold expansion found on TCPS (p < 0.05). The greater fold expansion of the cells on PDO and L-PLA films may be attributed to the availability of space for cells to grow, since their numbers at the start of culture were fewer following the 8 h attachment period. This suggests that regardless of initial seeding density on these degradable polymer substrates (i.e., if some minimum number of cells are able to attach), they will eventually populate the surfaces of all these polymers given sufficient space and time.


Subject(s)
Cartilage, Articular/cytology , Cell Adhesion , Chondrocytes/cytology , Polymers/metabolism , Cell Division , Cells, Cultured , Dioxanes/metabolism , Humans , Kinetics , Membrane Proteins/metabolism , Microscopy, Electron, Scanning , Polyesters/metabolism , Polymers/chemistry , Time Factors
5.
Drug Chem Toxicol ; 22(3): 481-9, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10445159

ABSTRACT

Standard regulatory toxicity tests are frequently supplemented with additional compound specific analysis. Analysis of hepatic cytochrome P-450 content, hepatic beta-oxidation activity (biochemical analysis), and cell proliferation rates are examples of these analyses that are included when past experience or similarity to other compounds, suggest that a presently tested compound may have an effect. Until now, separate subsets of animals have been designated for cell proliferation analysis and biochemical analysis, because it was unknown if implantation of 5-bromo-2'deoxyuridine (BrdU) filled osmotic pumps (BrdU implants) would effect the rate of hepatic-beta or hepatic cytochrome P-450 content. The purpose of the current study was to determine if BrdU implants had an effect on hepatic cytochrome P-450 content, beta-oxidation activity, or the measurement of these enzymes in rats and mice. The BrdU was administered through subcutaneous osmotic pump implants. The rate of hepatic peroxisomal beta-oxidation was not altered in male or female rats or mice with the BrdU implants when compared to those of the control groups. The total hepatic cytochrome P-450 content was also not altered in male or female rats or mice with the BrdU implants when compared to those of the control groups. BrdU implants do not appear to have an effect on the rate of hepatic peroxisomal beta-oxidation or the total hepatic cytochrome P-450 content in male or female rats and mice. It can be concluded that in future studies, rats or mice which are designated for cell proliferation analysis using BrdU implants are also suitable for use in evaluating chemically induced effects on hepatic peroxisomal beta-oxidation activity and/or total hepatic cytochrome P-450 content.


Subject(s)
Bromodeoxyuridine/toxicity , Cytochrome P-450 Enzyme System/analysis , Drug Implants , Liver/drug effects , Microbodies/drug effects , Animals , Bromodeoxyuridine/administration & dosage , Female , Liver/metabolism , Male , Mice , Mice, Inbred ICR , Microbodies/metabolism , Organ Size/drug effects , Oxidation-Reduction , Rats , Rats, Sprague-Dawley
6.
J Nurs Adm ; 29(5): 21-7, 1999 May.
Article in English | MEDLINE | ID: mdl-10333858

ABSTRACT

OBJECTIVE: The authors determine the effect of patient-focused redesign on midlevel nurse managers' role responsibilities and perceptions of work environment. BACKGROUND: Patient-focused redesign models have been initiated in a number of hospitals over the past 10 years. Few studies of the impact of these models on nurse leaders' roles and work responsibilities have been conducted. METHODS: Nine midlevel nurse managers were interviewed about their redesigned leadership roles and the challenges they experienced in implementing patient-focused redesign. RESULTS: Several themes emerged from the data. These themes focused on role change, ambiguity, position power, and environmental uncertainty and turbulence. Each of the nurse managers described feelings of frustration, disconnectedness, and inadequacy and spoke of how difficult it was to be the central figure in the eye of the storm. They noted that previously successful administrative strategies were not producing the same effect as in the past. CONCLUSION: This study provides beginning information about the magnitude of the impact of organizational redesign on midlevel nurse managers. Midlevel managers in this study struggled to keep up with the demands of the change and their own recognition of the importance of remaining committed to the uncertain goals of the institution. They were frustrated by their perceived inability to fix the situation and to meet the multiple needs of the staff. Nonetheless, they supported senior executives and attempted reasonable solutions to the problem.


Subject(s)
Nurse Administrators/organization & administration , Nursing Service, Hospital/organization & administration , Patient-Centered Care/organization & administration , Work , Humans , Leadership , Midwestern United States , Nurse Administrators/psychology , Organizational Innovation , Self Concept , Work/psychology
7.
J Urban Health ; 75(4): 903-10, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9854251

ABSTRACT

To describe practice trends for total abdominal hysterectomy (TAH) and supracervical abdominal hysterectomy (SCH) in New York State and to identify fiscal features associated with these two operations, all inpatient discharges for TAH and SCH performed for benign indications from 1990 to 1996 were reviewed using the Statewide Planning and Resource Cooperative System, a centralized data reporting system. For each year examined, the number of TAHs and SCHs performed, the procedure rates adjusted for the total New York State female population, and the per diem charge (calculated from mean institutional charge as a function of average length of stay) were evaluated. While the TAH rate declined in New York State, from 34.0 in 1990 to 28.4 in 1996 (P = .01), the SCH rate increased nearly five-fold during the same period, from 0.62 to 3.07 (P = .0003). Patients tended to be discharged later following SCH than for TAH, although by 1996, the LOS for both operations was equivalent. The per diem institutional charge for SCH was consistently higher than for TAH in each year studied. The changes in charge and relative frequency of TAH and SCH in New York State invite further study to describe these trends more fully.


Subject(s)
Hospital Costs/statistics & numerical data , Hysterectomy/economics , Hysterectomy/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Female , Health Care Surveys , Hospitalization/statistics & numerical data , Hospitalization/trends , Humans , New York , Patient Discharge
8.
J Prof Nurs ; 13(3): 160-7, 1997.
Article in English | MEDLINE | ID: mdl-9167405

ABSTRACT

Critical thinking is now an explicit National League for Nursing outcome requirement for nursing education programs, and all nursing faculty currently are expected to teach and evaluate critical thinking. However, most of the related literature is theoretical and not on the practical level that might be directly usable by faculty. This article presents a beginning framework developed by a faculty task force at the Indiana University School of Nursing for teaching and evaluating critical thinking. The conceptual definition of critical thinking underlying the framework reflects the efforts of several hundred experts from various disciplines, is maximally inclusive, and lends itself well to operationalization in the nursing context. The task force made two assumptions for this project: first, that the principles of rational thinking are essentially the same at every educational level, although the expertise expected of students at different educational levels certainly differs; and, second, that at this time a focus on operational as opposed to theoretical definitions for the six identified components of critical thinking (interpretation, analysis, evaluation, inference, explanation, and self-regulation) would be particularly useful for faculty and student understanding.


Subject(s)
Curriculum , Education, Nursing , Problem Solving , Thinking , Educational Measurement , Humans , Logic , Models, Educational , Program Development
9.
Biotechnol Prog ; 12(6): 837-46, 1996.
Article in English | MEDLINE | ID: mdl-8983208

ABSTRACT

Controlled secretion processes for the production of secretory proteins in monolayer culture have been described previously (Grampp et al. Adv. Biochem. Eng./ Biotechnol. 1992, 46, 35-62), but little is known about the feasibility of scaling such processes into high-density bioreactors. Two immobilized-cell, ceramic-matrix bioreactor configurations were tested using the beta TC-3 cell model system which, in monolayer culture, can be manipulated to secrete murine insulin in a highly controlled manner. One reactor was configured with an external recirculation reservoir for oxygen transfer and was operated as a conventional immobilized bed/recycle reactor. The other reactor was configured as a single-pass perfusion system with oxygen supplied by diffusion from silicone tubing positioned proximal to the porous walls of the ceramic matrix. After inoculation with beta TC-3 cells, both systems were perfused with serum-supplemented medium to stimulate cell growth, and they ultimately attained high densities (approximately 5 x 10(8) cells/mL of pore volume). To initiate controlled secretion operations, the reactor cores were washed with a serum-free basal medium, then exposed to a serum-free discharging medium containing secretory stimulants. Following several hours of discharging, the reactors were washed again, then switched to a serum-containing medium designed to quench the regulated secretion process. For the single-pass reactor these cycling operations were simple to implement and were effective in promoting the cyclic discharge and recharge of murine insulin. Because of the ability to reduce the perfusion rate in the single-pass reactor independent of oxygen transfer, the discharged insulin was captured in a relatively small volume (2 reactor core hold-up volumes), yielding a mean product concentration 10-fold greater than in the steady-state perfusate. Cyclic operation of the recirculating reactor was more difficult due to the complexity of switching between recirculation reservoirs, and the introduction of air bubbles during such operations resulted in the loss of biomass from the reactor after one cycle. Even in the first discharging cycle, the insulin yield was much lower than in the perfusate from the single-pass reactor, despite the comparable metabolic rates. The single-pass reactor was cycled successfully through four discharging and recharging episodes and maintained its ability to discharge insulin, albeit at a slower rate after the first discharge. Overall, 50-60% of the insulin secreted during the 48 h cycles was recovered during the brief discharging episodes. When insulin secretion rates and discharging yields were normalized to metabolic activity, neither high-density reactor system performed as well as did identically treated control T-flask cultures. It is hypothesized that the productivity and responsiveness of the high-density, pore-immobilized beta TC-3 cells are lower than in monolayer culture.


Subject(s)
Bioreactors , Insulin/metabolism , Animals , Cell Line , Culture Media , Glucose/metabolism , Insulin Secretion , Kinetics , Lactic Acid/metabolism , Mice
10.
Obstet Gynecol ; 87(5 Pt 1): 664-7, 1996 May.
Article in English | MEDLINE | ID: mdl-8677064

ABSTRACT

OBJECTIVE: To assess the effectiveness of a joint-specialty society and health department statewide peer-review program to reduce cesarean rates. METHODS: Forty-five of the 165 hospitals with active delivery services were reviewed between 1989 and 1993. Differences in total and repeat cesarean rates and vaginal birth after cesarean (VBAC) rates were compared by hospital review status using Student t tests and linear regression for the years before and after completion of the program. RESULTS: Reviewed hospitals reduced their total cesarean rate by 3% and repeat cesarean rate by 0.7%, and increased their VBAC rate by 14.6% compared with nonreviewed hospitals, for which the respective reduction in rates was 1%, 0.6%, and 12.7%. Statistically, there was no difference between reviewed and nonreviewed hospitals in terms of rate changes. CONCLUSION: This joint-specialty society and health department peer review had no apparent impact on cesarean rates.


Subject(s)
Cesarean Section, Repeat/statistics & numerical data , Cesarean Section/statistics & numerical data , Peer Review, Health Care , Vaginal Birth after Cesarean/statistics & numerical data , Female , Humans , Linear Models , New York/epidemiology , Pregnancy , Societies, Medical
11.
Arch Pediatr Adolesc Med ; 149(10): 1123-9, 1995 Oct.
Article in English | MEDLINE | ID: mdl-7550816

ABSTRACT

OBJECTIVES: To investigate an apparent decline in the rate of infantile hypertrophic pyloric stenosis (IHPS) and to examine the characteristics of children with IHPS and any associated malformations. DESIGN: Cohort study in which children with IHPS were compared with the population of live births. Trends of IHPS were compared in two data sets: a population-based birth defects registry and hospital discharge data. PARTICIPANTS: Children with IHPS identified from a birth defects registry and the population of live-born infants born to residents of New York State from 1983 to 1990. MAIN OUTCOME MEASURE: Trends in the incidence of IHPS in the two data sets, and demographic characteristics and malformations associated with IHPS. RESULTS: The rate of IHPS declined from 2.4 per 1000 live births in 1984 to 1.7 in 1990. White race and male gender were associated with a higher occurrence of IHPS; high birth order, older maternal age, higher maternal education, and low birth weight were associated with lower occurrence. Seven percent of children with IHPS had a major malformation compared with 3.7% of the general population. Three major malformations occurred more frequently in children with IHPS: intestinal malrotation, obstructive defects of the urinary tract, and esophageal atresia. Fewer cases were found in the birth defects registry than in the hospital discharge data. CONCLUSIONS: Underreporting of IHPS to the birth defects registry accounts for some of the decline. Children with IHPS have more major malformations than the general population, although some of the excess could be attributed to increased detection. Further investigation is needed into the environmental factors, especially socioeconomic, associated with IHPS.


Subject(s)
Pyloric Stenosis/epidemiology , Case-Control Studies , Cohort Studies , Congenital Abnormalities/epidemiology , Female , Humans , Hypertrophy , Incidence , Infant, Newborn , Logistic Models , Male , New York/epidemiology , Odds Ratio , Population Surveillance , Pyloric Stenosis/complications , Pyloric Stenosis/pathology , Registries , Risk Factors , Sex Distribution
12.
J Comp Neurol ; 359(4): 573-85, 1995 Sep 04.
Article in English | MEDLINE | ID: mdl-7499548

ABSTRACT

Experimental lesions have been widely used to induce neuronal degeneration and to test the ability to trophic molecules to prevent lesion-induced alterations, but these studies have not demonstrated unequivocally that afflicted neurons die as a result of these manipulations. The documentation of neuronal death in the above-described models and the time when it occurs after injury are crucial for the interpretation of trophic effects. In the present study, we combined multiple approaches to investigate the nature of retrograde neuronal changes in cholinergic neurons of the medial septal nucleus (MSN) after complete, unilateral transection of the fimbria-fornix (F-F). Projections neurons of the MSN were prelabeled with the fluorescent tracer Fluoro-gold (FG) 1 week prior to lesion. By counting both FG-labeled and choline acetyltransferase (ChAT)-immunoreactive neurons in the MSN at multiple time points postaxotomy, we differentiated the phenotypic response to injury from the degenerative process and established a critical time between the third and fourth weeks postaxotomy, during which approximately 50% of fluorescent perikarya disappear. Working in the previous time window, we identified dying cells by electron microscopy (EM) and terminal transferase-mediated (TdT) deoxyuridine triphosphate (d-UTP)-biotin nick end labeling (TUNEL) and showed that MSN neurons die via apoptosis, beginning at 16 days postaxotomy. An additional group of animals was allowed to survive for 1 month (i.e., 10 days after cell death has been completed); during this period, animals were treated with intraventricular nerve growth factor (NGF). Quantitative analysis of surviving cholinergic perikarya showed that NGF prevented degeneration of the majority of neurons. In concert, the results of the present study establish that NGF does not merely protect the phenotype but also prevents cell death in lesioned central cholinergic neurons.


Subject(s)
Acetylcholine/physiology , Apoptosis/drug effects , Nerve Degeneration/physiology , Nerve Growth Factors/pharmacology , Neurons/drug effects , Stilbamidines , Animals , Axons/physiology , Biotin/chemistry , Choline O-Acetyltransferase/analysis , Deoxyuracil Nucleotides/chemistry , Fluorescent Dyes , Immunohistochemistry , Male , Neurons/pathology , Rats , Rats, Sprague-Dawley , Septal Nuclei/chemistry , Septal Nuclei/cytology
13.
Med Group Manage J ; 42(4): 94, 96, 98 passim, 1995.
Article in English | MEDLINE | ID: mdl-10144248

ABSTRACT

In an environment of constant change, effective management decisions are harder to make. Physicians and clinic managers often miss valuable information from one key group--the patients. Their input builds a framework for sound solutions. The most efficient, unbiased collection method is a patient satisfaction study. With guidance from some one who is experienced in survey design and handling, physicians and managers will find these studies are easy to administer, are tools for learning and help build patient loyalty. Effectively designed studies give proportion to issues raised by patients. This information helps physicians and managers make good decisions on practice style, operations and service delivery. In the two case studies of primary care practices included in this article, the physician partners had very different issues of concern than the patients did. Without the studies, the physicians might have made poor decisions on the future of their clinics. Insurance providers recommend regular satisfaction studies to measure quality improvements, a clinic's strengths and weaknesses, and the patients' expectations. Patients are your lifetime partners and have valuable information for the survival of a practice. They help define where a practice is and where it should be.


Subject(s)
Group Practice/standards , Patient Satisfaction , Appointments and Schedules , Data Collection , Group Practice/organization & administration , Health Services Research , Oregon , Physician-Patient Relations , Professional-Patient Relations , Time Management
14.
J Geriatr Psychiatry Neurol ; 8(2): 125-31, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7794478

ABSTRACT

The pathologic diagnosis of Alzheimer's disease (AD) rests upon the identification of senile plaques and neurofibrillary tangles (NFT) in brain tissue. Methods for staining these structures vary in their sensitivity. Six different silver stains and immunocytochemistry for the beta-amyloid (A beta) peptide were compared for sensitivity in staining of plaques and tangles. For staining of plaques, the silver stains fell into two groups: one group stained primarily large, distorted neurites in classic plaques, and the other stained primarily fine, filamentous elements in diffuse plaques and at the periphery of classic plaques. Our recently developed "quick silver" method demonstrated the highest number of plaques. Sensitivity of NFT staining also varied considerably. The quick silver and Yamamoto-Hirano methods were best for staining both plaques and NFT.


Subject(s)
Alzheimer Disease/diagnosis , Alzheimer Disease/pathology , Brain/pathology , Neurofibrillary Tangles/pathology , Adolescent , Adult , Aged , Brain/ultrastructure , Culture Techniques , Female , Humans , Immunohistochemistry , Male , Middle Aged , Neurofibrillary Tangles/ultrastructure
16.
Biotechnol Bioeng ; 40(9): 1056-68, 1992 Nov.
Article in English | MEDLINE | ID: mdl-18601214

ABSTRACT

A single-pass, plug-flow bioreactor has been developed in which oxygen is supplied to entrapped hybridoma cells via silicone tubes threaded through the square channels of a macroporous ceramic monolith. Oxygen diffuses from the gas phase, through the silicone tubing, across the open square channel, and into the pores of the ceramic wall where it is consumed by entrapped cells. Advantages of such a reactor include higher product yields, protection of cells from detrimental hydrodynamic effects, no internal moving parts to compromise asepsis, and simplicity of operation. A prototype bioreactor was constructed and operated over a range of residence times. A side-by-side experimental comparison with a conventional recycle bioreactor was performed by inoculating both bioreactors with cells from the same stock culture and feeding medium from the same reservoir. Final antibody titers were 80% higher in the single-pass bioreactor at a residence time of 200 minutes compared with those of the recycle bioreactor at a residence time of 800 minutes. A theoretical analysis of oxygen transport in this bioreactor is developed to highlight important design criteria and operating strategies for scale-up.

17.
Fundam Appl Toxicol ; 19(4): 590-7, 1992 Nov.
Article in English | MEDLINE | ID: mdl-1426718

ABSTRACT

Wyeth-14,643 (WY) belongs to a diverse class of compounds which have been shown to produce hepatic peroxisome proliferation and hepatocellular carcinoma in rodents. Based on a review of bioassay data, a relationship appears to exist between peroxisome proliferating compounds and Leydig cell adenoma formation. Most rat bioassays with peroxisome proliferators have been conducted in the Fisher-344 (F344) rat, which has a high spontaneous incidence of Leydig cell adenomas. Thus, it was necessary to use an alternative animal model to investigate this relationship further. Therefore the Crl:CD BR (CD) rat, which has a low spontaneous Leydig cell adenoma incidence, was chosen for a 2-year feeding study with WY. Before initiating this 2-year feeding study, it was necessary to investigate whether any strain differences existed between CD and F344 rats with respect to WY-induced peroxisome and cell proliferation. In this study, male CD and F344 rats were fed diets containing 0, 50, or 1000 ppm WY for 21 days. Peroxisome proliferation in the liver and testis was determined biochemically by measuring beta-oxidation activity and was confirmed ultrastructurally. Serum hormone levels and cell proliferation rates in the liver and testis were also measured. In addition, basal beta-oxidation activity and cell proliferation rates were compared between the CD and F344 rats. A significant decrease in final body weight was observed in the 1000 ppm WY groups for both CD and F344 rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Anticholesteremic Agents/pharmacology , Pyrimidines/pharmacology , Animals , Body Weight/drug effects , Leydig Cells/drug effects , Leydig Cells/metabolism , Liver/drug effects , Liver/metabolism , Male , Microbodies/drug effects , Organ Size/drug effects , Oxidation-Reduction , Rats , Rats, Inbred F344 , Rats, Inbred Strains , Species Specificity
18.
Mutat Res ; 270(2): 201-9, 1992 Nov 16.
Article in English | MEDLINE | ID: mdl-1383737

ABSTRACT

Recently in vitro assays of mutagenesis have been criticized as being poorly predictive of long-term in vivo rodent assays of carcinogenicity. Questions have also been raised concerning the relevance of rodent assays to human risk. In vitro assays using mammalian cells can detect most types of genetic lesions thought to be important in human malignant disease. Molecular and cytogenetic analyses of mutations induced by a variety of genotoxic compounds at the heterozygous thymidine kinase locus in mouse lymphoma cells indicate that this in vitro assay does indeed register the range of genetic lesions recently found in a wide variety of human tumors. The types and complexity of the induced lesions are reflected in mutant colony phenotype in a compound-specific fashion. These studies point to the use of appropriate in vitro mammalian mutagenesis assays as new model systems for dissecting the genetic lesions important in human carcinogenesis, and as a means of determining the potential for compounds to induce such lesions.


Subject(s)
Carcinogenicity Tests , Models, Genetic , Mutagenicity Tests , Animals , Genes/drug effects , Genotype , Humans , Mammals , Mice , Phenotype , Thymidine Kinase/genetics
19.
J Neurol Sci ; 106(2): 221-9, 1991 Dec.
Article in English | MEDLINE | ID: mdl-1802970

ABSTRACT

The present study tested aspects of a novel etiological/pathogenetic hypothesis of Alzheimer's disease (AD), which proposes that alterations in endocrine regulation of peripheral calcium/phosphate (Ca/PO4) homeostasis (e.g., by glucocorticoids, vitamin D, etc.) induce and/or reflect altered calcium homeostasis and neurotoxicity in brain neurons. Two key predictions of this hypothesis were tested, namely that: (1) alterations in serum Ca and/or PO4 regulation should be present before or near the onset of AD and (2) these alterations should be found consistently in subjects with unconfounded AD. Previous studies have sought evidence of changes in Ca regulation primarily late in the disease, and usually in severely demented, thin and immobile inpatients in whom Ca/PO4 measures are likely to be confounded. In the present study, only mobile, relatively healthy, adequately nourished outpatients with probable AD were selected. In comparison to age-matched controls or demented subjects with even mild indications of vascular contributions, the AD subjects were characterized by lower serum PO4 and, to a lesser degree, lower serum Ca as well as a higher chloride/PO4 ratio. On serum chemistry tests from the first stages of AD (within 1 or 3 years after the onset of cognitive symptoms), these changes in serum PO4/Ca were as pronounced as they were later in the disease. Moderately low values of either PO4, Ca, or both (below -1.0 S.D. from the control group mean) identified 74% of all AD subjects and 100% of early onset AD subjects, in comparison to only 46% of mixed/vascular dementia subjects and 31% of normal age-matched controls. Thus, the results were consistent with the predictions and may have significant etiological/pathogenetic implications. If larger tests confirm these frequencies, serum Ca/PO4 indices may also prove useful in differential diagnosis.


Subject(s)
Alzheimer Disease/physiopathology , Calcium/blood , Phosphates/blood , Aged , Alzheimer Disease/blood , Alzheimer Disease/etiology , Blood Glucose/metabolism , Blood Pressure , Cholesterol/blood , Female , Follow-Up Studies , Humans , Male
20.
Genomics ; 10(3): 827-30, 1991 Jul.
Article in English | MEDLINE | ID: mdl-1889822

ABSTRACT

We report the cytogenetic mapping of the thymidine kinase (tk-1) gene in the mouse using two complementary and independent analyses: (1) investigation of chromosome aberrations associated with tk-1 gene inactivation in the L5178Y TK+/- -3.7.2C cell line, and (2) fluorescence in situ molecular hybridization of cloned tk-1 cDNA probes to mitotic chromosomes of this cell line. The consensus location from both analyses is 11E1-E2. Consideration of the mouse tk-1 gene localization, along with evidence that the homologous human TK1 gene is located distally on the large arm of chromosome 17, appears to extend the region of homology between MMU11 and HSA17 to the distal end of both chromosomes.


Subject(s)
Mice/genetics , Thymidine Kinase/genetics , Animals , Chromosome Aberrations , Chromosome Mapping , Genes , Genes, Neoplasm , Leukemia L5178/genetics , Leukemia L5178/pathology , Tumor Cells, Cultured
SELECTION OF CITATIONS
SEARCH DETAIL
...