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Biomedical subjects

S Levin

Publications and source records attributed to S Levin.

At least 19 recordsLinked to original sources

[Therapy related alterations to the thyroid gland].

Therapy related alterations to the thyroid gland are associated with more or less specific morphological changes. The therapy (thyrostatic drugs, radio-iodine) may be administered for the treatment of thyroid dysfunction (hyperthyroidism), or the thyroid gland is involved during or after the treatment (irradiation, various drugs) of primarily non-thyroid related diseases. The present review summarizes the most important morphological changes related to therapy.

Amiodarone↗

Prevalence and fluconazole susceptibility of Candida species recovered from the oropharynx of healthcare workers (HCWs) and non-HCWs.

We compared oropharyngeal cultures and fluconazole susceptibility for Candida in 100 healthcare workers (HCWs) and 100 non-HCWs. Isolates were identified using standard microbiological methods. Susceptibility was determined by Etest and microtiter method. There was no significant difference in prevalence or species of oropharyngeal Candida between HCWs and non-HCWs. Fluconazole resistance was infrequent.

Allied Health Personnel↗

Single- and repeated-dose pharmacokinetics of eplerenone, a selective aldosterone receptor blocker, in rats.

1. The pharmacokinetics of eplerenone (EP) were examined in rats following single or repeated dosing with (14)C-labelled or unlabelled EP to characterize absorption, metabolism and excretion. Rates of EP metabolism and cytochrome P450 activities were determined in vitro after repeated dose administration of EP. 2. Following a single i.v. dose (15 mg kg(-1)), the elimination half-life of EP was 0.80 and 1.14 h in male and female rats, respectively. Plasma clearances (CL) of EP were 1.62 and 1.20 l kg(-1) h(-1) in males and females, respectively. Following a single oral dose (15 mg kg(-1)), C(max) and T(max) of EP were 1.71 micro g ml(-1) and 0.5 h in male rats. The corresponding values in female rats were 3.54 micro g ml(-1) and 1.0 h. The systemic availability of EP was 25.6% in male rats and 66.4% in female rats, demonstrating sex differences in the pharmacokinetics of EP. 3. In the 8-day study, the AUC(0-24h)'s of total EP (closed lactone ring form plus open form) following 100 and 200 mg kg(-1) oral doses were approximately half those on day 1 in male rats. After repeated dosing for 13 weeks, the pharmacokinetics of total EP did not change with study duration at the 20 mg kg(-1) dose in both males and females. However, at the 100 mg kg(-1) dose, AUC(0-24h)'s were notably reduced on day 24 but progressively increased on subsequent days to approximate day 1 levels by day 86 in both sexes. At the 500 mg kg(-1) dose, the AUCs on day 86 remained lower than those on day 1. Reductions in AUCs on days 8 and 24 appeared to be the result of metabolism induction. 4. EP was extensively metabolized in male rats and most faecal and urinary radioactivity was in the form of metabolites. In female rats, the vast majority of urine and faecal radioactivity was associated with total EP. Thus, the sex difference in the pharmakokinetics of EP was due to more extensive metabolism in male rats. 5. The major metabolite in the rat was 6beta-OH EP. EP 6beta-hydroxylase activity was well correlated with testosterone 6beta-hydroxylase activity, indicating that EP metabolism to 6beta-OH EP was mediated primarily by CYP3A in the rat. 6. After repeated dose administration, EP increased 6beta-hydroxylase activities of testosterone and EP itself in a dose-dependent manner in both male and female rats, indicating that EP was a CYP3A inducer in the rat. There appeared to be no effects on activities of CYP1A1, 2B and 2E1.

Administration, Oral↗

Increasing asthma awareness among physicians: impact on patient management and satisfaction.

Our objective was to investigate the impact of increased asthma awareness among primary care physicians on the asthma control and satisfaction of their patients. Physicians attended an asthma education session with emphasis on patient-physician partnership followed by 4 month monitored follow-up of patients aged 5-44 years with mild to moderate asthma. Findings were compared with a group of patients whose physician attended the session but did not participate in the follow-up and two other control groups. The study included pediatricians and general practitioners of Maccabi Healthcare Services and their patients. Asthma symptoms were rated by patients and physicians. Data on drug prescription and use were derived from the Maccabi central database. Patient response and satisfaction and physician satisfaction were evaluated by telephone interviews. Mean asthma symptom score improved from 2.0 to 1.1 in the study group of patients (p < 0.001). The use of reliever drugs decreased concomitantly with a rise in controller drugs in all patients. An improvement in asthma status was reported by 64% of the study patients and 39% of non-participating patients (p = 0.007). Fifty-eight percent of the patients rated their competence to deal with asthma as high before the intervention compared to 62% of the participating and 55% of the non-participating patients after the intervention (p = 0.002). Most physicians claimed that simply increasing their awareness on asthma led to beneficial results in their patients. Physician education followed by monitored follow-up enhanced asthma control and patient satisfaction. Nevertheless, physician education alone appears to have a significant isolated impact on asthma control.

Adolescent↗

Ultra-relativistic electrons in Jupiter's radiation belts.

Ground-based observations have shown that Jupiter is a two-component source of microwave radio emission: thermal atmospheric emission and synchrotron emission from energetic electrons spiralling in Jupiter's magnetic field. Later in situ measurements confirmed the existence of Jupiter's high-energy electron-radiation belts, with evidence for electrons at energies up to 20[?]MeV. Although most radiation belt models predict electrons at higher energies, adiabatic diffusion theory can account only for energies up to around 20[?]MeV. Unambiguous evidence for more energetic electrons is lacking. Here we report observations of 13.8[?]GHz synchrotron emission that confirm the presence of electrons with energies up to 50[?]MeV; the data were collected during the Cassini fly-by of Jupiter. These energetic electrons may be repeatedly accelerated through an interaction with plasma waves, which can transfer energy into the electrons. Preliminary comparison of our data with model results suggests that electrons with energies of less than 20[?]MeV are more numerous than previously believed.

Journal Article↗

Neuronal hyperexcitability induced by repeated brief episodes of hypoxia in rat hippocampal slices: involvement of ionotropic glutamate receptors and L-type Ca(2+) channels.

Repeated exposures of rat hippocampal slices to short episodes of hypoxia induce a sustained decrease in the threshold of the development of stimulus-evoked epileptiform discharges in CA1 pyramidal neurons. We have previously demonstrated that the K(+)(o)-induced hyperexcitability required functional L-type voltage-dependent Ca(2+) channels and NMDA-receptors, but was independent of AMPA/kainate-receptor activation. As hypoxia/ischaemia can lead to increased K(+)(o), the epileptiform activity observed after exposure to these challenges could also result from high K(+)(o). The purpose of this study was: (i) to determine whether ionotropic glutamate receptors and L-type Ca(2+) channels are involved in the development of epileptiform activity induced by repeated exposures of hippocampal slices to hypoxia; and (ii) to compare the properties of hypoxia- and high K(+)(o)-induced hyperexcitability. Population spike of presynaptic fibres with field excitatory postsynaptic potential from the stratum radiatum, and population spike of CA1 pyramidal neurons from the stratum pyramidale, were recorded simultaneously in the CA1 area of rat hippocampal slices in response to electrical stimulation of the Schaffer collateral/commissural fibres. Repeated, brief hypoxic episodes induced a sustained decrease in the threshold for development of evoked epileptiform discharges that was associated with long-term potentiation of the CA3-CA1 synapses, but without EPSP-spike potentiation (i.e. in contrast to high K(+)(o)-induced hyperexcitability). The selective antagonist of NMDA receptors, D-APV (25 microM), and the selective blocker of L-type Ca(2+) channels, nifedipine (10 microM) depressed the development of hypoxia-induced hyperexcitability. However, in contrast to high K(+)(o)-induced hyperexcitability, hypoxia-induced hyperexcitability was also blocked by the AMPA/kainite-receptor antagonist, CNQX (5 microM). The present findings confirm that repeated, brief episodes of hypoxia, like exposure to high extracellular K(+), can induce a pro-epileptic state in the CA1 neuronal network, but that the mechanisms leading to hyperexcitability are different for the two stimuli.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Geographic variation in cardiovascular disease risk factors among American Indians and comparisons with the corresponding state populations.

OBJECTIVES: (1) To compare the prevalence of self-reported CVD, diabetes, hypertension, fair/poor perceived health status, and current tobacco use from three surveys of American Indians - two in the Southeast (Catawba Diabetes and Health Survey [CDHS] and Lumbee Diabetes and Health Survey [LDHS]) and one in the upper Midwest (Inter-Tribal Heart Project [ITHP]). (2) To compare the prevalence estimates from the CDHS, LDHS, ITHP with those for the corresponding state populations (South Carolina, North Carolina, Minnesota and Wisconsin, respectively) derived from the Behavioral Risk Factor Surveillance System (BRFSS). METHODS: Pearson's Chi-square analyses were used to detect statistically significant differences in the age-adjusted prevalence estimates across the study populations. RESULTS: Among these three populations of American Indians, the ITHP participants had the highest prevalence estimates of diabetes (20.1%) and current cigarette smoking (62.8%). The CDHS participants had the highest prevalence estimate of fair/poor perceived health status (32.0%). The LDHS participants had the highest prevalence estimate of chewing tobacco use (14.0%), and the lowest prevalence of CVD. The prevalence estimates of self-reported diabetes were dramatically higher among American Indian participants in the ITHP (20.1%) and CDHS (14.9%) than among participants in the corresponding state BRFSS (5.8% MN and WI and 6.6% SC), as were the estimates for hypertension. CONCLUSION: The substantial variations in prevalence of CVD and its risk factors among Tribal Nations suggests that distinct cultural norms, historic conditions, and important health issues of each American Indian community must be recognized and incorporated into all health promotion programs and policies.

Adult↗

Infectious complications of solid organ transplantations.

The rate of infectious complications in SOT recipients has declined dramatically. As improvements in immunosuppressive therapy, surgical techniques, and diagnostics and antimicrobial treatment continue, further declines in infectious complications are expected. Refinements to preemptive therapy for high-risk patients are likely to contribute further to this decrease. Further investigation is required to define what role various infectious agents play in chronic allograft injury and rejection.

Anti-Infective Agents↗

Tacrolimus conversion improves hyperlipidemic states in stable liver transplant recipients.

With improvements in surgical technique and the advent of new and more effective immunosuppressive agents, survival rates in liver transplant recipients have dramatically improved. However, hyperlipidemia frequently develops in patients administered cyclosporine-based immunosuppression long-term, although it appears to occur less often with newer, tacrolimus-based regimens. We sought to determine whether an isolated change in the baseline immunosuppressive regimen (cyclosporine to tacrolimus) would improve hyperlipidemic states in these patients. Twenty-one long-term stable liver transplant recipients with hyperlipidemia, manifested by elevated cholesterol and/or triglyceride levels, were offered conversion to tacrolimus from cyclosporine A therapy. Lipid profiles were monitored at baseline (while on cyclosporine therapy) and at 1 and 3 months after conversion to tacrolimus therapy. There were no other medication manipulations. After conversion to tacrolimus therapy, mean cholesterol levels decreased from 251 to 202 mg/dL at 1 month (P <.001) and 194 mg/dL at 3 months (P <.001). Similarly, triglyceride levels decreased from 300 to 207 mg/dL by 1 month (P =.011) and 203 mg/dL by 3 months (P <.001). There was also a statistically significant decrease for very low-density lipoprotein levels at 3 months (P =.005) and low-density lipoprotein levels at 1 and 3 months (P =.013 and P =.014, respectively). High-density lipoprotein levels did not significantly change after conversion to tacrolimus therapy. Conversion was not accompanied by adverse side effects, and patients tolerated the change well. In conclusion, simple conversion from cyclosporine to tacrolimus-based immunosuppression therapy is safe and improves posttransplantation hyperlipidemia in a subgroup of liver transplant recipients.

Cholesterol↗

A randomized clinical trial comparing the efficacy of mandibular implant-supported overdentures and conventional dentures in diabetic patients. Part IV: Comparisons of dietary intake.

STATEMENT OF PROBLEM: It is unclear whether the replacement of conventional mandibular dentures with implant-supported overdentures alters the diet and thus improves the nutritional intake of edentulous persons. PURPOSE: The purpose of this study was to compare the pretreatment and posttreatment diets of edentulous diabetic patients who received new dentures with either a conventional complete mandibular denture (CD) or a mandibular implant-supported overdenture (IOD). MATERIAL AND METHODS: New dentures were made for 89 edentulous diabetic patients with acceptable metabolic control without insulin (NIT) or with insulin (IT). A randomized approach was used to assign 37 patients a mandibular CD and 52 patients a mandibular IOD supported by 2 cylindrical implants. Of the 89 patients, 58 submitted a dietary log for 7 consecutive days before treatment (PT) and 6 months after treatment completion (PTC). An average daily intake of 28 essential nutrients was determined for each patient at each time interval. Separate 2 x 2 x 2 repeated analysis of variance (ANOVA) tests were performed for each nutrient to compare the means of the 2 denture groups (CD and IOD), 2 diabetic groups (NIT and IT), and 2 time intervals (PT and PTC). The intakes were also compared with the recommended daily allowance (RDA). RESULTS: ANOVAs for all 28 nutritional variables showed no main effect for either denture type or diabetic treatment. Time effects were seen for magnesium, potassium, copper, and monounsaturated fats. The PTC mean intake of the total sample (N = 58) decreased for all 3 minerals and increased for monounsaturated fats with study dentures. Post hoc tests showed the differences between PT and PTC means to be statistically significant for only magnesium (P=.043) and potassium (P=.015). The percentage of patients with PT intake 25% or more below the RDA ranged from 33% to 85% in the CD group and from 24% to 100% in the IOD group for the same 11 nutrients. PTC fiber intake deficiency was noted in almost all participants. Carbohydrate consumption was markedly lower than that recommended by the American Diabetic Association. CONCLUSION: As is often the case with elderly groups, this group of edentulous diabetic patients showed highly comprised nutritional intakes of fiber, vitamins, and minerals. The replacement of old dentures with new dentures that included either a mandibular CD or IOD did not alter patient diets such that the patients improved their nutritional intakes of essential micronutrients and macronutrients.

Aged↗

Wound-induced angiogenesis and its pharmacologic inhibition in a murine model.

BACKGROUND: A novel synthetic compound, SU5416, inhibits subcutaneous tumor growth of cells. Because angiogenesis in tumor growth and wound healing involves similar mechanisms, we examined whether SU5416 inhibits wound-induced angiogenesis. METHODS: Sixteen female BALB/c mice were randomized to receive either SU5416 (n = 8) or vehicle alone (n = 8) on day -2. On day 0, transparent window chambers were implanted into the dorsal skin flap. Treatment was stopped on day 7. On days 1, 7, and 14, micrographs of the windows were taken and microvessel density was estimated. RESULTS: On day 1, no statistically significant difference was noted between the microvessel density in controls and treatments. After the mice underwent treatment from day -2 to day 7 and microvessel densities were analyzed on day 7, angiogenesis was significantly inhibited in the SU5416 group (P <.001). Seven days after cessation of treatment, however, the SU5416 group showed complete recovery in angiogenesis. The increase in microvessel density in the SU5416 group on day 14 from day 7 was not significantly different from that of the control group (P >.05). CONCLUSIONS: We observed that SU5416, a known inhibitor of tumor-induced angiogenesis, also inhibited wound-induced angiogenesis in our murine wound model. This inhibitory effect is significant while the mice are undergoing treatment.

Angiogenesis Inhibitors↗

Eplerenone: a selective aldosterone receptor antagonist (SARA).

Aldosterone, the final product of the renin-angiotensin-aldosterone system (RAAS), is a mineralocorticoid hormone that classically acts, via the mineralocorticoid (aldosterone) receptor, on epithelia of the kidneys, colon, and sweat glands to maintain electrolyte homeostasis. Aldosterone has also been shown to act at nonepithelial sites where it can contribute to cardiovascular disease such as hypertension, stroke, malignant nephrosclerosis, cardiac fibrosis, ventricular hypertrophy, and myocardial necrosis. Although angiotensin-converting enzyme (ACE) inhibitors and angiotensin type 1 (AT(1)) receptor antagonists act to suppress the RAAS, these agents do not adequately control plasma aldosterone levels--a phenomenon termed "aldosterone synthesis escape." Spironolactone, a nonselective aldosterone receptor antagonist, is an effective agent to suppress the actions of aldosterone; its use is, however, associated with progestational and antiandrogenic side effects due to its promiscuous binding to other steroid receptors. For these reasons, eplerenone--the first agent of a new class of drugs known as the selective aldosterone receptor antagonists (SARAs)--is under development. In rodent models, eplerenone provides marked protection against vascular injury in the kidney and heart. In phase II clinical trials, eplerenone demonstrates 24-h control of blood pressure with once or twice daily dosing, and is safe and well tolerated in patients with heart failure when given with standard of care agents. Pharmacokinetic studies reveal that eplerenone has good bioavailability with low protein binding, good plasma exposure, and is highly metabolized to inactive metabolites and excreted principally in the bile. Eplerenone is well tolerated in acute and chronic safety pharmacology studies. Ongoing phase III trials of eplerenone in the treatment of hypertension and heart failure are underway. These studies will extend our understanding of selective aldosterone receptor antagonism in the treatment of chronic cardiovascular disease.

Animals↗

Racial/ethnic health disparities in South Carolina and the role of rural locality and educational attainment.

BACKGROUND: The prevalence of selected health indicators were compared among the Catawba Indians, African Americans, and whites in South Carolina, considering the possible role of rural locality and education. METHODS: Catawba members were respondents of a 1998 survey (N = 808). Other South Carolina residents were respondents of the 1995-1997 Behavioral Risk Factor Survey (4,150 whites and 1,413 African Americans). Prevalence of cardiovascular disease, diabetes, hypertension, overweight, poor health, smoking, physical inactivity, and poor diet were compared among the racial/ethnic groups. Logistic regression analyses were conducted within strata of urban/rural locality and education to determine whether these factors were associated with the adverse health indicators. RESULTS: Both Catawba and African Americans had higher prevalence of diabetes, hypertension, overweight, poor health, physical inactivity, and poor diet than whites. In addition, prevalence of diabetes, poor health, smoking, and poor diet were higher among the Catawba than among African Americans. Restricting the analyses to comparisons within urban/rural locality had little effect, whereas restricting the analyses to comparisons by education level eliminated many of the disparities among those with low education. CONCLUSIONS: Prevalence of chronic disease and adverse health behavior are higher among the Catawba than among other residents of South Carolina, especially compared with white residents.

Adult↗

Unusual renal features of Lowe syndrome in a mildly affected boy.

The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder characterized by congenital cataracts, mental retardation, and renal tubular dysfunction. The gene responsible for OCRL was identified by positional cloning and encodes a lipid phosphatase, phosphatidylinositol 4,5, bisphosphate [PtdIns(4,5)P2]5-phosphatase, which localizes to the Golgi apparatus and is suspected to play a role in Golgi vesicular transport [Suchy et al., 1995]. In addition to the ocular and renal manifestations, most boys with OCRL have cognitive problems and maladaptive behaviors including tantrums and stereotypies. We report a boy with a history of congenital cataracts and mild developmental delay who was also found to have hematuria with proteinuria but minimal signs of renal tubular dysfunction. Subsequent renal biopsy was compatible with a diagnosis of a noncomplement fixating chronic glomerulonephritis. Despite the atypical renal findings, skin fibroblast analysis for PtdIns (4,5)P2 5-phosphatase was performed, and enzyme activity was low, consistent with the diagnosis of OCRL. Western blot analysis from cell lysates showed the ocrl protein was decreased in size and amount. Our report shows atypical renal features of OCRL in a mildly affected boy. The possibility of OCRL should be considered in boys with cataracts and glomerular disease, even in the absence of renal tubular defects and frank mental retardation usually associated with the syndrome. Am. J. Med. Genet. 95:461-466, 2000. Published Wiley-Liss, Inc.

Acidosis, Renal Tubular↗

Lessons on pattern formation from planet WATOR.

It is well known that if reacting species experience unequal diffusion rates, then dynamics that lead to a constant steady state in a "well-mixed" environment can in a spatial setting lead to interesting patterns. In this paper, we focus on complementary pattern formation mechanisms that operate even when the diffusion rates are equal. In particular, we can say that when the mean-field ODE has an attracting periodic orbit then the stochastic spatial model will have large-scale spatial structures in equilibrium. We explore this mechanism in depth through the dynamics of the simulator WATOR.

Animals↗

Ecology. The value of nature and the nature of value.

Ecosystems are capital assets: When properly managed, they yield a flow of vital goods and services. Relative to other forms of capital, however, ecosystems are poorly understood, scarcely monitored, and--in many important cases--undergoing rapid degradation. The process of economic valuation could greatly improve stewardship. This potential is now being realized with innovative financial instruments and institutional arrangements.

Australia↗

Comparison of the enantioseparation of racemic uridine analogs on Whelk-O 1 and ChiralPak-AD columns.

The commercially available, brush-type (S,S)-Whelk-O 1 chiral stationary phase (CSP) has been used to separate 10 racemates of structurally related uridine analogs, potentially anti-viral agents, under various mobile phase compositions, using various temperatures. The enantioseparation was evaluated by comparing the Whelk-O 1 column performance with that of ChiralPak-AD column, reported previously. The comparison involved the role of some distinctive structural features of the racemates, type and composition of the solvent modifiers, as well as effect of temperature on the chiral discrimination. Despite the fact that both columns separate almost all the uridine analogs, significant differences were observed in their chiral recognition, as revealed from their retention, selectivity, resolution and elution order. The chiral recognition processes, responsible for enantioseparation on the Whelk-O 1 column, were relatively more systematic and easier to manipulate than on ChiralPak-AD column. Enantioseparation on the latter are of more complex nature and frequently gave results that were contradictory to the expectations. On the other hand, the performance in the ChiralPak-AD column was superior to that of the Whelk-O 1 column. Limitations in column handling and maintenance (pressure and temperatures) as well as limited solvent choice lead to the preference of the Whelk-O 1 column, in spite of its lower (but adequate) performance.

Chromatography, High Pressure Liquid↗