Effect of maternal diabetes on the expression of genes regulating fetal brain glucose uptake.

Diabetes alters adult brain glucose uptake and glucose transporter 1 gene expression. To investigate the effect of diabetes on genes regulating fetal brain glucose uptake, we examined the effect of moderate (blood glucose 10-16.7 mM, normoinsulinemia) and severe (blood glucose > 16.8 mM, hypoinsulinemia) maternal diabetes on the expression of genes regulating fetal brain glucose uptake in the genetically nonobese diabetic mouse. In the moderately diabetic state, a 50% decline in fetal brain GLUT1 mRNA levels was associated with a 20% increase in the corresponding GLUT1 protein levels. Simultaneously, although fetal brain GLUT3 mRNA and protein levels were barely detectable, no change in hexokinase I enzyme mRNA, protein (115,000 and 100,000 M(r)) or activity, was noted. In the severe form of maternal diabetes GLUT1 protein was unchanged, GLUT3 protein levels remained low, and a 2- to 3-fold increase in the lower molecular form of the hexokinase I protein (100,000 M(r)) and enzyme activity occurred. These observations suggest that moderate and severe forms of maternal diabetes do not affect the fetal brain glucose transporter levels to a physiologically significant extent. The severe form of maternal diabetes, however, enhances 1.5- to 3-fold the expression and activity of hexokinase I. This enzyme mediates the rate-limiting step in brain glucose metabolism, namely the intracellular conversion of glucose to glucose-6-phosphate.

Toxicity evaluation of petroleum blending streams: reproductive and developmental effects of light catalytic cracked naphtha distillate in rats.

A distillate of light catalytic cracked naphtha (CAS number 64741-55-5, LCCN-D), administered by inhalation, was tested for reproductive and developmental toxicity in Sprague-Dawley rats, following a modified OECD Guideline 421, Reproductive/Developmental Toxicity Screening Protocol. LCCN-D was administered as a vapor, 6 h/d, 7 d/wk at target concentrations of 0, 750, 2500 or 7500 ppm to female rats for approximately 7 wk from 2 wk prior to mating, during mating through gestational d 19, and to males beginning 2 wk prior to mating for 8 consecutive weeks. Dams and litters were sacrificed on postnatal d 4, and males were sacrificed within the following week. Parental systemic effects observed at the 7500 ppm exposure level were increased kidney weights and relative liver weights in males and increased spleen weights in high-dose females. Livers and spleens from rats in the high-dose group were normal in appearance at necropsy. IncreaSed kidney weights in high-dose males were indicative of male-rat-specific light hydrocarbon nephropathy. No test-related microscopic changes were observed in the reproductive organs or nasal turbinate tissues of either sex. Reproductive performance was unaffected by treatment with LCCN-D. Fertility index was > or =90% in all dose groups. There were no exposure-related differences in implantation sites and live pups per litter, and no gross abnormalities were observed. Pups born from treated dams showed comparable body weights and weight gains to controls. The viability index on postpartum d 4 was > or =97%; the high-dose group had more male than female pups at birth and at d 4 postpartum. Under the conditions of this study, the no-observable-adverse-effect level (NOAEL) for exposure to light catalytic cracked naphtha distillate for parental toxicity was 2500 ppm and the NOAEL for reproductive performance and developmental toxicity was 7500 ppm.

ABC estimation of unit costs for emergency department services.

Rapid evolution of the health care industry forces managers to make cost-effective decisions. Typical hospital cost accounting systems do not provide emergency department managers with the information needed, but emergency department settings are so complex and dynamic as to make the more accurate activity-based costing (ABC) system prohibitively expensive. Through judicious use of the available traditional cost accounting information and simple computer spreadsheets. managers may approximate the decision-guiding information that would result from the much more costly and time-consuming implementation of ABC.

Using microcomputers to improve capital decision making.

Health care organizations have traditionally selected capital projects based on subjective measures such as medical staff priority, accreditation criteria, and regulations. In some cases, basic qualitative measures, such as payback period or profitability indices, have been used. The expected reduction in available capital that will result from changes in Medicare reimbursement and from managed care, as well as increased competition, will require health care decision makers to adopt more sophisticated methods of capital project evaluation in the future if they expect their organizations to remain viable. This article demonstrates, through the use of microcomputers and commonly used spreadsheet software, that the capital selection decision process can be improved and the optimal combination of projects, from a financial perspective, selected.

Satisfaction of patients in two Air Force family practice programs.

This study was carried out to determine of patients enrolled in family practice clinics were satisfied with their care and to ascertain if there was a difference in the level of satisfaction between two groups of family practice patients: one group at a teaching medical center and the other at a general acute care community hospital. The overwhelming majority of family practice patients surveyed were extremely satisfied with the care they were receiving. The prime reasons for this satisfaction were physician continuity (having one physician for the whole family), personal attention, and having levels of satisfaction between the groups at a teaching and a non-teaching facility. Overall, families that had received preventive health instructions from their physician had a stronger desire to remain with family practice and had fewer dislikes about the program than did the group of patients who had not received any preventive health instructions from their physician.

Objective risk adjustment improves calculated ROI for capital projects.

Most healthcare organizations can ill afford to assume risk for which they are inadequately compensated. When capital projects are being considered, factoring risk with an adjustment to the projected cost of capital can increase the calculated return on investment and improve the net present value of anticipated cash flow. This adjustment factor, however, should reflect the capital structure of the organization, historical average returns, and variance in the context of the market, the specific industry, and similar projects being considered.

Improving communication among health professionals through education: a pilot study.

Communication can be thought of as a message that is sent, received, and understood. Each discipline of the health profession has its own jargon and means of expressing ideas in shorthand. These separate forms of communicating are effective among those of the same background but are often at the root of misunderstandings between professional groups. This article reviews communication theory and traces the difficulties created when inter-disciplinary teams of healthcare try to work together and communicate. As multi-disciplinary teams are increasingly dealing with the complex problems of today's healthcare system, clear communication and understanding has never been more important. If educators could assist in creating an understanding of vocabulary used for decision processes, communication could improve. The authors of this study performed a multi-stage Delphi survey that grouped terms used by administrators and clinicians and produced a lexicon of corresponding terms. An expert panel then reviewed and modified the list. The result is a lexicon that can be useful to assist clinicians and administrators to communicate with each other. By utilizing clinical terminology, or vice versa, instead of management or clinical jargon, some of the translation done by administration or clinicians could be reduced. Examples of how the lexicon can be utilized are provided in the article. This includes using it in health administration education to demonstrate the variances in clinical/managerial terms. It could also be provided as a primer to physicians, nurses, and other health professionals who assume administrative positions to enhance their communication with administrators.

Comparative 90-day dietary study of paraffin wax in Fischer-344 and Sprague-Dawley rats.

Highly refined mineral hydrocarbons (MHCs) such as low melting point paraffin wax (LMPW) and low viscosity white oils can cause inflammatory changes in the liver and mesenteric lymph nodes (MLNs) of the Fischer-344 (F-344) rat. In contrast, only minimal MLN changes are seen in the Sprague-Dawley (S-D) rat with no changes in the liver. In this study, the response of female F-344 and S-D rats was compared after 90days dietary treatment with 0%, 0.2% or 2% LMPW. Effects in the F-344 rats were significantly greater than in the S-D rats: increased liver and splenic weights and inflammatory changes (hepatic microgranulomas) in these tissues were observed only in the F-344 rats. Microgranulomas in the MLNs were observed in both strains but the effects were substantially greater in the F-344 rats. Cellular markers of inflammation were examined in a subset of rats from each group using immunohistochemical staining. An increase in staining for CD3 (T-cells), CD8a (suppresser/cytotoxic T-cells) and CD4 (helper T-cells) correlated with an increase in lymphoid cells in the livers of treated F-344 rats. The majority of macrophages in the hepatic microgranulomas of treated F-344 rats were negative for the ED2 marker, indicating a likely origin from non-resident macrophages. Electron microscopy showed Kupffer cell hypertrophy and hyperplasia in treated F-344 rats. However, lysozyme staining (indicating activation of epithelioid macrophages) decreased with increasing granuloma size. Non-ED2 expressing cells may have been recruited but not sufficiently activated to be lysozyme positive. Inflammatory changes in the cardiac mitral valve noted in previous studies of LMPW were also seen in the F-344 rats in this study but not in the S-D rats. Chemical analysis showed that MHC accumulated in livers from treated F-344 but not S-D rats and the concentration was more than 2-fold greater in MLNs from the F-344 than from the S-D rats. The F-344 appears to be more immunologically sensitive to a number of agents than other rat strains and the results of this study suggest that this may contribute, along with pharmacokinetic differences, to the inflammatory response of F-344 rats to dietary MHCs.

Using time management to achieve balance.

A recent MGMA survey showed work-life balance as the number one issue facing group practice managers. This article explains techniques from the field of time management that will enable group practice managers to gain control of their schedules, reduce time pressures and stress and increase productivity. The article covers: goal setting, daily lists, handling paperwork, delegating and limiting involvement, socializing, communicating, overachieving, planning, writing, telephone calling, attending meetings, reading, financial planning, developing a philosophy, involving family, evaluating skills and teaching time management to employees.

Improving productivity in academic group practice.

The purposes of this article are to identify all the variables that impact productivity in a group practice, contrast the administrator's and physician's definitions of productivity, discuss current measurement tools and outline the steps in a traditional productivity project. The article identifies key variables that management must address: physician education, goals, feedback and rewards that are critical to the success of any productivity undertaking. Upon completion of this article, the reader will be able to understand the differences in the way administrators and physicians view productivity and be able to identify the vital areas that must be addressed in any effort to increase productivity. While the article focuses on the academic setting, the principles are applicable in any group practice.

Reproductive and developmental toxicity studies of a linear alkylbenzene mixture in rats.

Alkylate 215, a mixture of linear decyl- to tridecylbenzenes, is an intermediate in the manufacture of detergent sulfonates. A two-generation reproduction study and a developmental toxicity study were conducted using single daily doses given by gastric intubation in a corn oil vehicle. In the reproduction study, groups of 30 rats/sex/group were given doses of 0, 5, 50, or 500 mg/kg/day. F0 animals received a 10-week premating treatment period and were then mated to produce a single litter; F1 adults were selected from the F1 litters. F1 animals were dosed for 11 weeks before mating to produce a single litter. Adults and weaned pups received a gross postmortem examination. Histopathology studies were conducted on reproductive tissues, tissues with gross lesions, and the pituitary gland taken from each adult in the control and high dose groups. In the developmental toxicity study, groups of 24 mated female rats were given 0, 125, 500, or 2000 mg/kg/day on Days 6 through 15 of gestation. Dams were terminated on gestation Day 20 and fetuses were examined for external, soft tissue, and skeletal defects. Results of the reproduction study were as follows. At 50 mg/kg/day, pup weights were decreased at Day 7 in the F1 litter. At 500 mg/kg/day, decreases were found in the F0 females in premating and early lactation weight gains; in both generations in premating weight gains in males and in weight gains during gestation in females; and in litter size, pup viability at birth, Day 0-4 survival, and pup weights on Days 14 and 21. The NOAEL for reproductive effects was 5 mg/kg/day. The developmental toxicity study found effects on several parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Methyl tertiary butyl ether inhalation in rats: a single generation reproduction study.

Male rats exposed to target concentrations of methyl tertiary butyl ether (MtBE) at 300, 1300 and 3400 ppm for 6 hours/day, 5 days/week for 12 weeks were mated to female rats exposed to the same concentrations for a 3-week period. Exposures continued through the mating period and the females continued exposures during gestation and from days 5-21 lactation of the litters (F1a) (no exposures days 0-4 lactation). A second litter (F1b) was produced under the same mating and post mating exposure regimen. No adverse effect of treatment was observed with the adult animals (Fo) throughout the in-life portion of the study. The only remarkable finding was an increased incidence of dilated renal pelves in the low- and high-dose females (Fo). All gonad weights, male accessory reproductive organ weights, organ-to-body weight ratios and reproductive organ histopathology were unremarkable upon comparison of treated animals with air sham controls. The mating indices and fertility indices in exposed animals for both mating intervals (F1a and F1b) were not significantly different from controls. Pregnancy rates were comparable between treated and control females for the first litter interval (F1a) but were slightly lower (not statistically significant) than control on the second litter interval (F1b). Treated animal mean gestation length and the mean number of pups at birth were not statistically different from controls. The pup viability indices at birth were comparable for control and treated groups for the F1a generation, but the mid- and high-dose groups displayed a slight statistically significant decrease in the F1b generation; the decrease was not considered to be biologically significant and perhaps not treatment-related. Litter survival indices were comparable between control and treated groups for both litter intervals. Pups of mid- and high-dose females had slightly lower (not statistically significant) mean weights at days 14 and 21 of lactation but this was not considered treatment-related. The most frequent post-mortem observation for pups sacrificed at day 21 of lactation was dilated renal pelves. This did not appear to be related to treatment. It is concluded that MtBE inhalation in rats results in little adverse reproductive toxicity as shown in a two litter, one generation reproduction assay in rats.

Effect of streptozotocin-induced maternal diabetes on fetal rat brain glucose transporters.

Glucose, an essential substrate for brain oxidative metabolism, is transported across the blood-brain barrier and into neuronal and glial cells via Glut 1 and Glut 3 facilitative glucose transporter isoforms. To examine the effect of excessive circulating glucose on fetal brain glucose transporter expression, we investigated the effect of streptozotocin-induced maternal diabetes (SEVERE-D; n = 29) on the 20-d gestation fetal rat brain Glut 1 and Glut 3. We studied the effect of streptozotocin alone (STZ-ND; n = 12) in a nondiabetic state as well, along with vehicle injected controls (C; n = 24). In the presence of fetal hyperglycemia (12.63 +/- 0.82 nM-SEVERE-D versus 2.35 +/- 0.28-STZ-ND and 2.42 +/- 0.16-C; p < 0.001) and hypoinsulinemia (0.38 +/- 0.03 nM-SEVERE-D versus 0.50 +/- 0.07-STZ-ND and 0.55 +/- 0.06-C; p < 0.02), no detectable change in fetal brain Glut 1 and Glut 3 pretranslational expression (transcription/elongation rates and corresponding steady state mRNA levels) was noted when simultaneously compared with the STZ-ND and C groups. In contrast, a trend toward a decline in Glut 1 (approximately 25 to 30%, p = 0.05) and a substantive decrease in Glut 3 (approximately 35 to 50%, p = 0.0006) protein concentrations was present in both the STZ-ND and SEVERE-D groups when compared with the C group. These observations support a chemical effect of streptozotocin independent of maternal diabetes upon the translation or posttranslational processing of fetal brain glucose transporters. Maternal diabetes with fetal hyperglycemia, however, failed to substantively alter fetal brain glucose transporters independent of the streptozotocin effects upon neuroectodermally derived tissues. We conclude that maternal diabetes with associated overt fetal hyperglycemia does not significantly change fetal brain glucose transporter levels.

Teratology evaluation of methyl tertiary butyl ether in rats and mice.

Mated CD Sprague-Dawley rats and CD-1 mice were exposed during the period of organogenesis to target concentrations of 0, 250, 1000, and 2500 ppm methyl t-butyl ether (MTBE). None of the control or test-group animals died during the treatment or posttreatment periods. Females were sacrificed on d 20 (rats) or d 18 (mice). No adverse effects of treatment were reflected in maternal parameters of body weight, water consumption, or liver weight or in physical examination data for either species. Food consumption fell in the groups of treated rats during d 9-12; similar but nonsignificant effects were observed for mice during d 12-15. In rats, no treatment-related changes were recorded in the uterine implantation data, fetal size parameters, or fetal sex distribution data. Examination of fetuses for external abnormalities, skeletal malformations, or ossification variations did not reveal any changes caused by MTBE exposure. A slight increase in fetal resorptions was observed in the groups of mice exposed to low and high concentrations; this increase was attributed to two females in each group that had an unusually high number of resorptions, rather than to the treatment itself. No significant effects were observed in any groups of treated mice on external and soft-tissue examination or evaluation of skeletal abnormalities or ossification variations. The incidence of fused sternebrae in the high-concentration group increased slightly, which might be attributed to fetotoxicity.

Effects of rate review on the financial viability of New York hospitals: a retrospective assessment.

This article reports the findings of a study analyzing the effects of rate setting on the financial condition of New York hospitals from 1974 to 1980. During this period, the New York rate review system was considered one of the most stringent--and successful--cost containment programs in the county. The conclusions of this study indicate that there may be serious long-term consequences of cost containment programs of this type.

Developmental toxicity of dimethylformamide in the rat following inhalation exposure.

Dimethylformamide (DMF) is a widely used industrial solvent. DMF has been reported to be a developmental toxin when given to rodents by injection or following dermal administration. In this study, groups of pregnant rats were exposed by inhalation to either 0 (control), 30, or 300 ppm DMF from gestation day 6 through 15. In the 300 ppm rats, both maternal weight gain during gestation and fetal weights were lower than those of the controls. Fetal resorptions were not increased in this group. No significant differences among either maternal or fetal rats were seen in the 30 ppm group compared to controls. Both fetal and maternal toxicity were noted at 300 ppm and the no observed effect level under these experimental conditions was 30 ppm for both the dams and the conceptuses. DMF did not produce malformations in the rat fetus even at a level that was toxic to the dam.

A two-generation reproduction study with monochlorobenzene vapor in rats.

Groups of 30 male and 30 female Sprague-Dawley CD rats, designated as the F0 generation, were exposed to vapor of monochlorobenzene (MCB) at target concentrations of 0, 50, 150, or 450 ppm for 10 weeks prior to mating and during mating, gestation, and lactation. The progeny of the F0 generation was designated as the F1 generation and groups of 30 male and 30 female F1 animals were exposed to the same concentrations of MCB as the F0 parents. Exposure of F1 animals was initiated 1 week postweaning and lasted 11 weeks prior to mating and through mating, gestation, and lactation. All F2 pups were observed through weaning at which time they were killed. Observations made during the study included body weights, food consumption, mating and fertility indices, pup and litter survival indices, and histopathology of selected tissues. No mortality was observed during the course of this study. Body weights and food consumption for all treated groups were comparable to controls during the growth period. Maternal body weight data during gestation and lactation were also comparable between the control and treated groups. Mating and fertility indices for males and females for both generations appeared unaffected by treatment. Pup and litter survival indices for all treated groups were comparable to those of controls. Hepatocellular hypertrophy and renal changes (tubular dilation with eosinophilic material, interstitial nephritis, and foci of regenerative epithelium) were observed among F0 and F1 male rats exposed to 150 and 450 ppm MCB.(ABSTRACT TRUNCATED AT 250 WORDS)

Subchronic inhalation toxicity and reproductive assessment in rats of three chlorinated propenes.

Groups of 15 male and 15 female Sprague-Dawley rats were exposed to 1 of 3 chloropropene (2,3-Di = DCP; 1,2,3-Tri = TRCP; and 1,1,2,3-Tetra = TECP) vapors to provide information on repeated exposures and the potential for reproductive impairment by the most likely route of occupational exposure. Target exposure concentrations were 0, 1, 5, and 15 ppm, 6 h/d, 5 d/wk for 13 wk. The following parameters were evaluated: pharmacotoxic signs, survival, body weights, hematology, clinical blood chemistry, urine analysis, gross and histopathology (over 40 tissues/rat), organ weights, and selected weight ratios. Signs of nasal irritation were noted in rats exposed to 15 ppm of either DCP or TRCP but not TECP. Small decreases in overall body weight were observed in female rats exposed to 15 ppm TCP. An increase (approximately 15%) in spleen weight, with no corresponding histopathological or clinical findings, was observed in 15 ppm DCP-treated male rats. No other effects considered related to treatment were observed following exposure to any of the three chlorinated propenes. Additional groups of 10 male and 20 female Sprague-Dawley rats were exposed to DCP, TRCP, or TECP vapors at target concentrations of 0, 1, or 5 ppm for 6 h/d, 5 d/wk for a 10-wk premating period, a mating period, and the first 14 d (females only) of gestation. Females were allowed to deliver litters and the offspring were evaluated during a 21-d lactation period. Mating, pregnancy, and fertility indices were generally comparable among all test groups, although female mating and pregnancy indices of both DCP-treated females were lower than expected in the regular and postrecovery reproduction phase. No effects were seen on pup survival, sex distribution, body weights, organ weights, and ratios. A modest reduction in pup body weights was observed following TECP exposure but was attributed to large litter size. No treatment-related effects were seen following necropsy of adults or weanlings, nor were such effects noted following microscopic evaluation of gonads from parental animals.

Chronic toxicity, oncogenic potential, and reproductive toxicity of p-nitroaniline in rats.

Dose levels for these studies were selected mainly on the basis of subchronic studies, although consideration was also given to workplace exposure levels and proposed mechanism of tumor formation with structurally similar compounds. For the chronic study, groups of 60 male and 60 female Sprague-Dawley CD (Registered Trademark of Charles River Breeding Laboratories, Portage, MI) rats were given 0, 0.25, 1.5, or 9.0 mg/kg/day paranitroaniline (PNA) by gavage in corn oil for a period of 2 years. Parameters monitored included clinical observations, ophthalmoscopic exams, body weights, food consumption, hematology, clinical chemistry, and urinalysis at regular intervals throughout the study. All gross lesions and over 40 tissues were examined histologically for all control and high-dosage-level animals. Gross lesions, spleens, and livers of low- and mid-dosage groups were also examined histologically. For the reproduction study, groups of 15 male and 30 female rats, designated as F0 generation, were given PNA at the same levels as the chronic study for 14 weeks prior to mating and during mating, gestation, and lactation. Selected groups of 15 male and 30 female rats of the F1 generation received the same dose of PNA for 18 weeks prior to mating and during mating, gestation, and lactation. F2 pups were observed through weaning at which time they were euthanized. Observations made during the study included body weights, food consumption, mating and fertility indices, pup and litter survival indices, and histopathology of selected tissues. In the chronic study, except for a slight decrease in survival of high-dose male rats late in the study, survival in all treated groups was comparable to controls. Blood methemoglobin levels were elevated in the mid- and high-dosage groups, while slight anemia was observed in the high-dosage group also. Spleen weights were significantly increased in the high-dosage groups. An accumulation of brown pigment was observed in the cytoplasm of the sinusoidal macrophages or littoral cells of the liver and in the reticuloendothelial cells of the spleen. No treatment-related increase in tumor incidence was observed. In the reproduction study, no consistent pattern of effect from treatment between the F0 and F1 generation was seen in mating, pregnancy, or fertility indices. Thus, administration of PNA at levels which produced significant methemoglobinemia and low-level anemia in the rat and histological changes in the spleen produced no tumors or reproducible effects on reproductive performance.