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Biomedical subjects

H Pohl

Publications and source records attributed to H Pohl.

At least 19 recordsLinked to original sources
PubMed2000

Vasoconstrictor responses in thromboxane receptor knockout mice: tubuloglomerular feedback and ureteral obstruction.

The role of thromboxane (TP) in the vasoconstriction induced by tubuloglomerular feedback or 18-h ureteral obstruction was studied in wild type mice (TP +/+), and in heterozygous (TP +/-) and homozygous TP receptor knockout mice (TPR -/-). TGF function was assessed from the response of stop flow pressure (PSF) to a maximum increase in loop of Henle flow rate (0-30 nL min-1). PSF fell by 6.4 +/- 0.4 mmHg in wild-type mice, by 6.1 +/- 0.6 mmHg in TP +/-, and by 7.9 +/- 0.7 mmHg in TP -/- mice. In the presence of the TP receptor agonist U46,619 (10-5 M) the PSF reduction increased to 10. 4 +/- 0.8 mmHg in TP +/+, and to 10.6 +/- 2.8 mmHg in TP +/-, but was unchanged at 7.7 +/- 0.7 mmHg in TP -/-. Mean arterial blood pressures were comparable between groups (103 +/- 3 mmHg in TP +/+, 113 +/- 4.6 in TP +/- and 113 +/- 2.4 mmHg in TP -/- mice). Intratubular pressure following unilateral ureteral obstruction was significantly higher in TP -/- than in TP +/+ mice both in the early phase (0-3 h) and late phase (18 h) of obstruction. These results indicate that chronic TP receptor deficiency does not significantly alter maximum TGF responses in mice, and that it is accompanied by exaggerated vasodilatation during short-term unilateral ureteral obstruction and attenuated vasoconstriction during longer lasting obstruction. We conclude that thromboxane is primarily a regulator of renal vascular tone under pathophysiological conditions.

Animals↗
PubMed2000

Circadian control of migratory restlessness and the effects of exogenous melatonin in the brambling, Fringilla montifringilla.

Circadian pacemakers control both "daytime" activity and nocturnal restlessness of migratory birds, and the daily rhythm of melatonin release from the pineal has been suggested to be involved in the control of migratory activity. To study the phase relations between the two activity components during entrainment and when free running, locomotor activity of bramblings (Fringilla montifringilla) was recorded continuously under a 12:12 "cool light" to "warm light" cycle (CL:WL, ca. 5,000 K and ca. 2,500 K, respectively) or blue light to red light cycle (BL:RL. maxima at 440 and 650 nm, respectively) at different irradiance ratios. Migratory activity was expressed primarily during the WL or RL phase of the light cycles. Under free-running conditions, the circadian periods tau correlated with the phase relations between day and night (migratory) activity components during preceding entrainment. Bramblings with migratory activity had significantly longer tau at constant light intensity than the same individuals without migratory activity. Birds with migratory activity reentrained faster after a 6h phase shift of the CL:WL cycle than birds without migratory activity. When exogenous melatonin was given in the drinking water (200 microg/mL 1% ethanol or 0.86 mM) to bramblings exposed to 12:12 CL:WL cycles with constant irradiance, the amounts of activity, which were initially higher during the WL phase of the light cycle, were suppressed to similar low levels during both light phases. The systematic changes in the amounts of activity during melatonin treatment were not correlated with consistent changes in entrainment status. The data support the hypothesis that changes in the amplitude and level of the daily melatonin cycle are involved in regulating migratory restlessness, by either allowing or inhibiting nocturnal activity.

Animals↗
PubMed1999

Spectral composition of light as a Zeitgeber for birds living in the high arctic summer.

The hypothesis was tested whether periodic changes in spectral composition of light are an effective zeitgeber for synchronization (entrainment) of circadian rhythms of birds breeding in the high arctic summer. Two palearctic passerine birds, the brambling (Fringilla montifringilla) and the common redpoll (Carduelis f. flammea), which both breed during summer at latitudes above the Arctic Circle and migrate to temperate zone latitudes for wintering, were studied. To investigate the effect of daily alterations in light spectrum, bramblings were tested under 24-h cycles of fluorescent lights of different color temperatures (12 h at ca 5,000 K and 12 h at ca 2,500 K) and energy ratios varying between 16:1 and 0.3:1. Entrainment of activity rhythms occurred at energy ratios of 1:1 (in all seven birds tested) and 0.8:1 (in three of seven birds tested) with activity mostly within the "blue" phase (ca 5,000 K). Light cycles alternating between narrow spectral ranges of blue (max. at 440 nm) and red (max. at 650 nm) and energy ratios of 1:1 and 1.1:1 (equivalent to ratios of photons flux of ca 0.67:1 and 0.73:1, respectively) were also effective in entraining the bramblings' activity rhythms (8 and 9 of 11 birds, respectively) with activity occurring primarily during the red phase. The activity rhythms of most common redpolls tested also entrained to blue:red light cycles (B:R 16.5:7.5 h) with equal energies during the blue and red phase (equivalent to a photons flux ratio of ca 0.67:1). The results support the hypothesis that passerine birds breeding in the arctic during summer may use the daily changes in spectal composition of sunlight as a zeitgeber for synchronizing physiological and behavioral rhythms, if changes in light intensity are not a reliable environmental cue.

Adaptation, Physiological↗
PubMed1998

Public health challenges posed by chemical mixtures.

Approximately 40 million people live within a 4-mile radius of waste sites that the Agency for Toxic Substances and Disease Registry (ATSDR) has assessed to date. Human populations living in the vicinity of such sites are often subjected to complex chemical exposures that may contribute to the total body burden of oxogenous chemicals. Apart from the contaminants found at waste sites, exposure may also include environmental, occupational, and personal agents. Concurrent exposure to chemicals such as welding fumes, indoor air pollutants, tobacco smoke, alcohol, and prescription and nonprescription drugs makes the health assessment of exposure to waste site chemicals a more complex task. Voluntary exposures such as these frequently entail exposures to relatively high chemical concentrations and can usually be well defined and quantified. Conversely, involuntary exposures from waste sites may be at low concentrations and hence difficult to characterize and quantify. Of the approximately 1450 waste sites evaluated by the ATSDR, 530 (37%) had either completed or potentially completed exposure pathways. Results of public health assessments conducted at 167 sites during 1993 to 1995 show that about 1.5 million people have been exposed to site-specific contaminants. At 10% or more of the sites that had either completed or potentially completed exposure pathways, 56 substances were identified. Of these, 19 are either known or anticipated human carcinogens, and 9 are associated with reproductive or endocrine-disrupting effects. In this paper we present important concerns regarding hazardous waste sites including the impact on human health, ecology, and quality of life. To address such human-health related issues, the ATSDR has established a mixtures program that consists of three components: trend analysis to identify combinations of chemicals of concern, experimental studies to identify data that would be useful in the development and implementation of predictive decision support methodologies, and development of assessment methodologies and guidance to provide health assessors with the tools to incorporate the evaluation of multiple-chemical exposure into site assessments.

Animals↗
PubMed1997

Medication-prescribing errors in a teaching hospital. A 9-year experience.

BACKGROUND: Improved understanding of medication prescribing errors should be useful in the design of error prevention strategies. OBJECTIVE: To report analysis of a 9-year experience with a systematic program of detecting, recording, and evaluating medication-prescribing errors in a teaching hospital. METHODS: All medication-prescribing errors with potential for adverse patient outcome detected and averted by staff pharmacists from January 1, 1987, through December 31, 1995, were systematically recorded and analyzed. Errors were evaluated by type of error, medication class involved, prescribing service, potential severity, time of day, and month. Data were analyzed to determine changes in medication-prescribing error frequency and characteristics occurring during the 9-year study period. RESULTS: A total of 11,186 confirmed medication-prescribing errors with potential for adverse patient consequences were detected and averted during the study period. The annual number of errors detected increased from 522 in the index year 1987 to 2115 in 1995. The rate of errors occurring per order written, per admission, and per patient-day, all increased significantly during the study duration (P < .001). Increased error rates were correlated with the number of admissions (P < .001). Antimicrobials, cardiovascular agents, gastrointestinal agents, and narcotics were the most common medication classes involved in errors. The most common type of errors were dosing errors, prescribing medications to which the patient was allergic, and prescribing inappropriate dosage forms. CONCLUSIONS: The results of this study suggest there may exist a progressively increasing risk of adverse drug events for hospitalized patients. The increased rate of errors is possibly associated with increases in the intensity of medical care and use of drug therapy. Limited changes in the characteristics of prescribing errors occurred, as similar type errors were found to be repeated with increasing frequency. New errors were encountered as new drug therapies were introduced. Health care practitioners and health care systems must incorporate adequate error reduction, prevention, and detection mechanisms into the routine provision of care.

Drug Prescriptions↗
PubMed1995

Public health assessment for dioxins exposure from soil.

Dioxins are among the most toxic anthropogenic chemicals in the environment. Their toxicity has been extensively studied in both humans and animals. Dioxin-contaminated soil may result in dioxins occurring in a food chain. This is especially important for the general population. It has been estimated that about 98% of exposure to dioxins is through the oral route. In the 1980s, a concentration level of 1 ppb 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in soil was specified as "a level of concern," based on cancer effects. However, recent studies indicate that end points other than cancer are also of concern. A health risk analysis scenario based on health effects of TCDD other than cancer is discussed and compared with the projected intake from 1 ppb TCDD in soil.

Biological Availability↗
PubMed1995

Halogenated aromatic hydrocarbons and toxicity equivalency factors (TEFs) from the public health assessment perspective.

The validity of the toxicity equivalency factors (TEFs) approach to predicting toxicity of mixtures was investigated on the basis of the public health risk assessment that had been posted for different groups of halogenated aromatic hydrocarbons. First, the minimal risk levels (MRLs) were derived based on the databases available for chlorinated dibenzo-p-dioxins (CDDs), chlorinated dibenzofurans (CDFs), and polychlorinated biphenyls (PCBs). The MRL values were then converted to 2,3,7,8-tetrachlorinated dibenzo-p-dioxin (TCDD) toxicity equivalents (TEQs) and compared with each other. There was a good correlation between intermediate duration oral MRLs for TCDD and 2,3,4,7,8-pentaCDF when expressed in TEQs (7 pg/kg/day and 15 pg/kg/day). Although the studies that served for derivation of these MRLs used different species (guinea pigs and rats, respectively), the toxicity endpoints (immunological and hepatic for TCDD and hepatic for 2,3,4,7,8-pentaCDF) were comparable. The hepatic effects were measured by the same techniques (blood chemistry and histopathology), ensuring similar sensitivity. However, there was a discrepancy between acute oral MRLs for TCDD and 2,3,4,7,8-pentaCDF when they were expressed in TEQs (20 pg/kg/day and 500 pg/kg/day, respectively). The studies used for MRL derivation involved not only different species (mice and guinea pigs, respectively), the immunotoxicity endpoints were measured by techniques with different sensitivity (serum complement activity versus histopathology), making comparison difficult. Further calculations showed that the TEFs approach may be feasible for individual coplanar congeners of PCBs, but not for a mixture of Aroclors. Correlations presented here support the concept that the TEFs are valid only if specific criteria for their derivation are met (e.g., a broad database of information, consistency across endpoints, additivity for the effects, a common mechanism of action, etc.). In environmental exposure, the total toxicity of halogenated aromatic hydrocarbons is not necessarily the sum of the total individual congener toxicities because individual congeners compete for the same receptor; therefore, nonadditive behavior may occur.

Animals↗
PubMed1994

Entrainment properties of the circadian system changing with reproductive state and molt in the canary.

Changes in entrainment properties of the circadian pacemaking system with respect to changes in reproductive state and molt were investigated in the male domestic canary (Serinus canaria). In two experiments canaries were subjected to three and two similar sequences of light regimens, respectively, during 1 year. Locomotor activity, feeding, and vocalization were simultaneously recorded. Only birds showing complete postnuptial wing feather molt and related changes in behavior (vocalization) expressed differences in the ability of their circadian system to entrain to low-amplitude light/dark (LD) cycles with periods (T) > 24 h. It is suggested that changes in the organization of the circadian system, including differences in entrainment properties, are associated with the state of photorefractoriness and related functions (testicular regression, postnuptial molt). Regardless of the molt status, over 90% of the birds that were arrhythmic in constant light (LL) entrained to low-amplitude LD cycles with T 25.5 h (Experiment 1) or T 25.0 h (Experiment 2). Birds that did not entrain or were relatively entrained with the respective light regimes were (with one exception) rhythmic in LL. It is therefore likely that the occurrence of arrhythmia in LL facilitates entrainment to low-amplitude light cycles.

Animals↗
PubMed1990

Medication prescribing errors in a teaching hospital.

A study of prescribing errors committed by physicians that occurred in a tertiary-care teaching hospital is reported. From a total of 289 411 medication orders written during the 1-year study period, 905 prescribing errors were detected and averted, of which 522 (57.7%) were rated as having potential for adverse consequences. The overall detected error rate was 3.13 errors for each 1000 orders written and a rate of 1.81 significant errors per 1000 orders. The error rate (4.01 per 1000 orders) was greatest between 12 pm and 3:59 pm. First-year postgraduate residents were found to have a higher error rate (4.25 per 1000 orders) than other prescriber classes, and obstetrics/gynecology services (3.54 per 1000 orders) and surgery/anesthesia services (3.42 per 1000 orders) had greater error rates than other services. The study results demonstrate the significant risk to patients from medication prescribing errors. Educational, operational, and risk-management activities should include efforts directed at reducing the risk to patients from prescribing errors.

Hospital Bed Capacity, 500 and over↗
PubMed1990

Increase in luteinizing hormone content occurs in cultured human fetal pituitary cells exposed to gonadotropin-releasing hormone.

To investigate the mechanisms by which GnRH regulates LH production during intrauterine life, dispersed pituitary cells from second trimester human fetuses were cultured on extracellular matrix-coated plates for 48 h. Exposure of cells to 3 x 10(-10) mol/L GnRH for 1-48 h significantly increased cumulative LH secretion compared to that in respective controls (P less than 0.01). The rate of GnRH-stimulated LH release was accelerated during the first 6 h, after which it declined to a level similar to that of basal release. This phenomenon was associated with a decrease in the GnRH concentration of the medium. Exposure of cells to GnRH (3 x 10(-10) to 10(-6) mol/L) for 48 h induced a dose-dependent elevation of total LH which correlated with an increase in releasable, but not cellular, LH. Desensitization to GnRH (10(-7) mol/L) occurred when cells were cultured with pharmacological amounts of GnRH for 48 h. These results indicate that GnRH induces the increase in total and releasable LH in human fetal pituitary cells. These cells also appear to inactivate GnRH. Thus, GnRH may increase LH production in the human fetal pituitary and the pituitary receptor mechanism may be involved in GnRH action on LH release during intrauterine life.

Cells, Cultured↗
PubMed1989

Vitamin C intake influences the bleomycin-induced chromosome damage assay: implications for detection of cancer susceptibility and chromosome breakage syndromes.

Supplementation with 1 g of vitamin C (ascorbic acid) per day decreased the amount of chromosome damage induced in lymphocytes by an exposure to bleomycin during the last 5 h of cell culture. We did not see such changes in lymphocytes from control individuals samples at the same time but not taking vitamin C supplements. This bleomycin assay has been proposed as a test for cancer susceptibility. A similar assay for genetic instability may be useful in detecting heterozygotes for chromosome-breakage syndromes (for example, Fanconi anemia or ataxia telangiectasia). Even though our sample size is small and our results should be interpreted cautiously, statistically significant effects were found with vitamin C supplementation. It would, therefore, be prudent to consider dietary and perhaps other lifestyle factors when interpreting of results from this bleomycin assay and related assays for genetic instability.

Ascorbic Acid↗