Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Candy”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 847 records · Page 47Linked to original sources
PubMed2004

Impact of initiating carvedilol before angiotensin-converting enzyme inhibitor therapy on cardiac function in newly diagnosed heart failure.

OBJECTIVES: The purpose of this research was to evaluate the therapeutic value of initiating a beta-blocker before an angiotensin-converting enzyme inhibitor (ACEI) in the treatment of heart failure. BACKGROUND: Although ACEI and carvedilol produce benefits in heart failure, whether the order of initiation of therapy determines the impact on left ventricular (LV) function and New York Heart Association functional class (NYHA FC) has not been determined. METHODS: A single-center, prospective, randomized, open-label study was performed. We evaluated whether initiation of therapy with carvedilol either before (n = 38) or after (n = 40) perindopril therapy in newly diagnosed patients in NYHA FC II to III heart failure with idiopathic dilated cardiomyopathy, with the addition of the alternative agent after six months, determined subsequent changes in NYHA FC and LV function (echocardiography and radionuclide ventriculography). Study drugs were titrated to maximum tolerable doses. RESULTS: There were no differences in baseline characteristics between the study groups. After 12 months 11 patients died (6 in the group where the ACEI was initiated). At 12 months the group receiving carvedilol as initial therapy achieved a higher tolerable dose of carvedilol (43 +/- 17 mg vs. 33 +/- 18 mg, p = 0.03); a lower dose of furosemide (p < 0.05); and better improvements in symptoms (NYHA FC, p < 0.002), LV ejection fraction (radionuclide: 15 +/- 16% vs. 6 +/- 13%, p < 0.05; echocardiographic, p < 0.01), and plasma N-terminal pro-brain natriuretic peptide concentrations (p < 0.02). CONCLUSIONS: As opposed to the conventional sequence of drug use in the treatment of heart failure, initiation of therapy with carvedilol before an ACEI results in higher tolerable doses of carvedilol and better improvements in FC and LV function.

Adolescent↗
PubMed2004

Systemic effects of allergen exposure on blood basophil IL-13 secretion and FcepsilonRIbeta.

BACKGROUND: Airway allergen challenge studies have shown the upregulation of cytokines in local airway tissues and distal effects on bone marrow precursors for eosinophils and basophils. OBJECTIVE: We investigated whether local intranasal allergen challenge alters the phenotype of circulating basophils to a primed state. METHODS: Ten subjects with allergic rhinitis were challenged with allergen by means of intranasal spray on 3 sequential days. Basophils were isolated from subjects before challenge and 3, 24, and 96 hours after the third allergen challenge. Basophils were compared before challenge and after the last allergen challenge for levels of FcepsilonRIbeta protein by means of Western blotting and for FcepsilonRIbeta mRNA expression by means of real-time PCR. Basophils were also compared with regard to spontaneous secretion of IL-4 and IL-13. RESULTS: Basophil FcepsilonRIbeta protein levels increased in 5 of 6 subjects after allergen challenge relative to before challenge. Likewise, basophil FcepsilonRIbeta mRNA levels increased a median of 2-fold after the last challenge relative to before challenge ( P=.007, n=9). IL-13 protein was detected in supernatants of 7 of 9 subjects' basophil-enriched cultures after the last challenge compared with 3 of 9 basophil-enriched cultures before challenge (median, 6.2 vs 0 pg/mL; P=.058). IL-4 was not detected in any culture supernatant. CONCLUSION: Intranasal allergen challenge transiently activates circulating basophils by increasing expression of the FcepsilonRIbeta subunit and spontaneous IL-13 secretion. Because FcepsilonRIbeta is an amplifier of FcepsilonRI-mediated responses and IL-13 is proinflammatory, these findings support a primed basophil functional state and demonstrate a systemic effect of local allergen challenge that could contribute in exacerbating allergic reactions.

Administration, Intranasal↗
PubMed2005

What advice do patients with infectious mononucleosis report being given by their general practitioner?

OBJECTIVE: The aim of this study was to describe the advice that patients with acute infectious mononucleosis recall having been given by their general practitioner (GP; family or primary care doctor). METHODS: Individuals with a recent diagnosis of infectious mononucleosis were recruited for a randomised controlled trial assessing the effectiveness of a brief educational intervention on recovery. All participants were asked at their initial assessment what advice that they had been given by their GP. They were not given any prompts and were free to give several responses. Responses were grouped into various themes. RESULTS: Seventy-one patients took part. Of these, 11 (15%) recalled being given no specific advice. Of the remaining 60 participants, 70% recalled being given advice to rest, or to "take it easy", usually without any qualification; 10% recalled being given dietary advice, and 17% advice on simple symptom management. CONCLUSION: The majority of individuals with recent onset infectious mononucleosis recall being given advice to rest by their GPs. This finding is discussed in relation to evidence suggesting that rest may be unhelpful.

Diet↗
PubMed2006

Knowledge and use of the internet as a source of controlled substances.

Despite growing evidence that the internet is a source of controlled substances for nonmedical use, there is a lack of information about who is using it to obtain these drugs. One hundred adult drug-dependent inpatients in a private residential treatment program participated in a semistructured interview regarding how they obtained their drugs. Twenty-nine percent reported knowledge of the internet as a source of drugs, and 11% reported that they had used the internet to either buy drugs or locate a drug dealer. The results of this preliminary study suggest that the internet has become a source of controlled substances for some addicted individuals. Considerations for future research and clinical practice are described.

Adult↗
PubMed2004

Phase I study of escalating doses of oxaliplatin in combination with fixed dose gemcitabine in patients with non-small cell lung cancer.

PURPOSE: Oxaliplatin (OHP) is a new platinum antineoplastic, while gemcitabine (GEM) is one of the most active drugs against non-small cell carcinoma (NSCLC). The OHP/GEM combination is interesting because the drugs have different mechanisms of action and toxicity profiles. The primary endpoint of this study was to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of OHP/GEM combination in non-small cell carcinoma of the lung. METHODS: Patients with relapsed NSCLC were treated with fixed dose i.v. GEM (1250 mg/m2) on days 1 and 8; followed on day 1 by i.v. OHP over 3 h, starting from 70 mg/m2 with 20 mg/m2 increments, up to 130 mg/m2. We enrolled 19 patients with eastern cooperative oncology group (ECOG) status 0/1=13/6; male/female=13/6. All had received first-line and four second-line chemotherapy. RESULTS: Four patients dropped out. At dose level 2, one patient died of pulmonary embolism; at level 3, two patients died of disease progression. One patient at level 3, refused to continue treatment after allergic reaction (high fever episode) during infusion of third cycle. Fifteen patients were evaluable for toxicity and response. According to a priori statistical considerations, three patients in each of the first three treatment levels and six in the last level were evaluable. No G3-4 toxicity was observed at levels 1 and 2. G3 neutropenia and anemia occurred in 8% of cycles at level 3. Six patients entered level 4 (OHP 130 mg/m2) with 22 courses delivered: G3-4 neutropenia occurred in 9%, G1-2 thrombocytopenia in 18%; other toxicities were mainly limited to G1-2 flu-like syndrome in about one third of patients and G1-2 nausea and vomiting in 5% of courses. There was no myelo-DLT at the highest dose level. There was no neurotoxicity at any level. Treatment was delayed in 12% and dose reduced in 26% of courses. There were 2/15 PR. CONCLUSIONS: MTD was not reached. OHP and GEM can probably be administered safely at 130 and 1250 mg/m2, respectively, as first-line therapy. The schedule is being used in a phase II trial.

Aged↗
PubMed2005

Functional human telomeres are recognized as DNA damage in G2 of the cell cycle.

Telomeres have to be distinguished from DNA breaks that initiate a DNA damage response. Proteins involved in the DNA damage response have previously been found at telomeres in transformed cells; however, the importance of these factors for telomere function has not been understood. Here, we show that telomeres of telomerase-negative primary cells recruit Mre11, phosphorylated NBS1, and ATM in every G2 phase of the cell cycle. This recruitment correlates with a partial release of telomeric POT1; moreover, telomeres were found to be accessible to modifying enzymes at this time in the cell cycle, suggesting that they are unprotected. Degradation of the MRN complex, as well as inhibition of ATM, led to telomere dysfunction. Consequentially, we propose that a localized DNA damage response at telomeres after replication is essential for recruiting the processing machinery that promotes formation of a chromosome end protection complex.

Cell Line↗
PubMed2006

Deficits across multiple cognitive domains in a subset of aged Fischer 344 rats.

Rodent models of cognitive aging routinely use spatial performance on the water maze to characterize medial temporal lobe integrity. Water maze performance is dependent upon this system and, as in the aged human population, individual differences in learning abilities are reliably observed among spatially characterized aged rats. However, unlike human aging in which cognitive deficits rarely occur in isolation, few non-spatial learning deficits have been identified in association with spatial impairment among aged rats. In this study, a subset of male aged Fischer 344 rats was impaired both in water maze and odor discrimination tasks, whereas other aged cohorts performed on par with young adult rats in both settings. The odor discrimination learning deficits were reliable across multiple problems. Moreover, these deficits were not a consequence of anosmia and were specific to olfactory learning, as cognitively impaired aged rats performed normally on an analogous non-olfactory discrimination task. These are among the first data to describe an aging model in which individual variability among aged rat cognition occurs across two independent behavioral domains.

Aging↗
PubMed2006

Epigenetic memory loss in aging oligodendrocytes in the corpus callosum.

In this study, we address the hypothesis that aging modifies the intrinsic properties of oligodendrocytes, the myelin-forming cells of the brain. According to our model, an "epigenetic memory" is stored in the chromatin of the oligodendrocyte lineage cells and is responsible for the maintenance of a mature phenotype, characterized by low levels of expression of transcriptional inhibitors. We report here an age-related decline of histone deacetylation and methylation, the molecular mechanisms responsible for the establishment and maintenance of this "epigenetic memory" of the differentiated state. We further show that lack of histone methylation and increased acetylation in mature oligodendrocytes are associated with global changes in gene expression, that include the re-expression of bHLH inhibitors (i.e. Hes5 and Id4) and precursor markers (i.e. Sox2). These changes characteristic of the "aging" oligodendrocytes can be recapitulated in vitro, by treating primary oligodendrocyte cultures with histone deacetylase inhibitors. Thus, we conclude that the "epigenetic memory loss" detected in white matter tracts of older mice induces global changes of gene expression that modify the intrinsic properties of aged oligodendrocytes and may functionally modulate the responsiveness of these cells to external stimuli.

Age Factors↗
PubMed2005

Accelerated satiation after duodenal switch.

BACKGROUND: This is to introduce a new test "negative alliesthesia" for measuring satiation after bariatric surgery. It is a test that is well known by physiologists but has never been used clinically. It is based on the observation that repeated pleasant gustatory stimuli turn into unpleasantness in the process of satiation. METHODS: We measured the time it took for a repeatedly ingested sweet stimulus to become first unpleasant (negative alliesthesia) and then intolerable (satiety). At the same time, we measured the degree of pleasure aroused by the sweet stimulus (hedonic rating). The test was given to 9 patients before and 3 and 6 months after the duodenal switch procedure and in 10 morbidly obese patients, three times, 3 months apart. RESULTS: The test showed that negative alliesthesia and satiety were three times faster after surgery. The negative alliesthesia time decreased from 16.0 +/- 3.9 minutes to 5.7 +/- 1.4 minutes (P < 0.0004). The satiety time decreased from 26.7 +/- 5.0 minutes to 10.7 +/- 1.3 minutes (P <0.001). Finally, the hedonic rating for the sweet stimulus decreased from 78.8% +/- 15.7% to 49.9% +/- 13.0% at 3 months and 39.3% +/- 20.6% at 6 months after surgery, without, however, reaching statistical significance. CONCLUSION: The duodenal switch modified negative alliesthesia. It is too soon to say what place this test may have in bariatric surgery, but its simplicity and ingenuity are attractive.

Adult↗
PubMed2005

Measurement of urinary excretion of 5-hydroxymethyluracil in human by GC/NICI/MS: correlation with cigarette smoking, urinary TBARS and etheno DNA adduct.

5-Hydroxymethyluracil (5-HMU) is derived from radiation in addition to endogenous oxidative DNA damage and it is one of the most abundant DNA adducts. Human 5-HMU-DNA-glycosylase has been shown to repair this lesion. Whether urinary levels of 5-HMU is a valid biomarker for oxidative DNA damage in vivo has been investigated. However, controversial results on its relation to cigarette smoking were reported. To facilitate analysis of urinary 5-HMU in epidemiological studies, a highly sensitive and specific assay based on stable isotope dilution gas chromatography/negative ion chemical ionization/mass spectrometry was developed. The limit of detection for N1,N3-bis(pentafluorobenzyl)-HMU is 10 fg (20 amol) (S/N=4) injected on column and the limit of quantification in urine was 0.7 nM of 5-HMU. Using as little as 10 microL of human urine samples, levels of urinary 5-HMU in 21 healthy volunteers were accurately quantified. No correlation was observed between urinary 5-HMU levels and cigarette smoking. However, there was a statistically significant association between urinary levels of 5-HMU and thiobarbituric acid-reactive substances (r=0.71, p=0.0003). In addition, urinary 5-HMU levels also correlated with urinary levels of 1,N6-ethenoadenine (r=0.54, p=0.01). These findings suggest that this assay should be valuable in assessing the role of urinary 5-HMU as a biomarker of oxidative DNA damage and repair.

Adenine↗
PubMed2005

VEGF directs newly gastrulated mesoderm to the endothelial lineage.

Herein, we investigated the role of VEGF signaling in the earliest events in vasculogenesis and found that it exerts critical effects shortly after mesodermal cells form by gastrulation. We showed that VEGF treatment of embryos caused an increase in the population of newly gastrulated mesodermal (NGM) cells that express the transcription factor TAL1. This increase in TAL1-positive cells was attributed to VEGF induction of VEGF receptor-2 (Flk1)-positive NGM cells that would normally not have been induced due to the limited availability of VEGF in the NGM. Evidence that VEGF-mediated induction of NGM cells is relevant to the endothelial lineage is the finding that induced TAL1-positive cells in the NGM formed ectopic structures whose cells exhibited characteristics of endothelial cells, including the ability to integrate into the vascular network and express the QH1 antigen. Finally, we showed that VEGF-induced TAL1 expression in the NGM which resulted in the formation of ectopic structures was mediated by Flk1 but not Flt1 signaling. In summary, we have established that VEGF signaling is critical to allocation of NGM to the endothelial lineage.

Animals↗
PubMed2006

Corticosterone in relation to body mass in Adelie penguins (Pygoscelis adeliae) affected by unusual sea ice conditions at Ross Island, Antarctica.

Penguins naturally fast each year during breeding and again whilst moulting, and may lose more than 40% of body mass during a fast. Fasting in emperor (Aptenodytes forsteri) and king (Aptenodytes patagonicus) penguins has been divided into three phases, with phase III characterised by an increased rate of body mass loss, increased plasma corticosterone concentrations, and a change in behaviour leading to abandonment of the breeding attempt and return to sea to feed. Initial corticosterone concentrations and corticosterone responses to a handling stressor were measured in the current study to determine if they increase during phase III of fasting in Adelie penguins (Pygoscelis adeliae). The study was conducted in 2001 at the northern Cape Bird colony on Ross Island, Antarctica. Penguin breeding on Ross Island was disrupted in the 2001-2002 summer by a large iceberg (B15A) which stopped the normal movement of sea ice in the Ross Sea. Penguins departing from the Cape Bird colony were lighter than returning or incubating birds (3.39+/-0.10cf. 4.16+/-0.06 and 4.07+/-0.08kg). It is likely that the departing birds were males that had been lighter than normal when they arrived at the colony. Initial plasma corticosterone concentrations were higher in departing than returning or incubating penguins (6.89+/-1.69cf. 2.36+/-0.42 and 1.08+/-0.19ng/ml). Corticosterone responses to handling were also greater in departing penguins. Initial plasma corticosterone, concentrations at 30min and total and corrected integrated corticosterone responses were inversely related to body mass in departing penguins, whereas there were no relationships in arriving penguins. beta-hydroxybutyrate and uric acid concentrations were consistent with departing birds having entered phase III of fasting. The results indicate that corticosterone and corticosterone responses are elevated in phase III of fasting in the Adelie penguin.

3-Hydroxybutyric Acid↗
PubMed2002

Effects of pentoxifylline on cytokine profiles and left ventricular performance in patients with decompensated congestive heart failure secondary to idiopathic dilated cardiomyopathy.

Patients with severe heart failure have plasma cytokine concentrations that are more than twofold greater than those in patients with moderate heart failure. Although pentoxifylline, an immunomodulatory agent that inhibits tumour necrosis factor-alpha (TNF-alpha) production, improves pump function in mild-to-moderate heart failure, its effects on advanced heart failure have not been determined. In a prospective, randomized, double-blind, placebo-controlled study we compared the effects of 1-month therapy with pentoxifylline (400 mg 3 times daily) (n = 9) and placebo (n = 9) on left ventricular systolic function and dimensions as well as on plasma TNF-alpha (picograms per milliliter), interleukin-10 (IL-10), and the apoptosis-signaling receptor Fas/Apo-1 in patients with idiopathic dilated cardiomyopathy and advanced heart failure. All patients had New York Heart Association functional class IV heart failure, required intravenous inotropic agents for >72 hours at the beginning of the study, and received diuretics, digoxin, and an angiotensin-converting enzyme inhibitor for the duration of the study. Marked increases in TNF-alpha and Fas/Apo-1 concentrations were noted in the 18 patients compared with patients with functional class II to III heart failure and controls (p <0.001). Baseline characteristics were the same between the pentoxifylline and placebo groups. Pentoxifylline administration resulted in reduced TNF-alpha and Fas/Apo-1 concentrations, and an increase in ejection fraction at 1 month (p <0.05 compared with baseline and with placebo), effects that were not observed in the placebo-treated group. These data suggest that pentoxifylline may be a useful adjunct to conventional therapy in patients with severe heart failure.

Adjuvants, Immunologic↗
PubMed1999

Association of left ventricular systolic performance and cavity size with angiotensin-converting enzyme genotype in idiopathic dilated cardiomyopathy.

The insertion-deletion (ID) polymorphism of the angiotensin-converting enzyme (ACE) gene is a marker linked to differences in plasma and cardiac ACE activity as well as to an increased mortality in patients with idiopathic heart failure. We examined the possibility that ACE gene ID variants are associated with differences in left ventricular (LV) systolic performance or internal LV dimensions in a high-risk cohort of patients with idiopathic dilated cardiomyopathy (IDC). The ACE genotype was determined in 171 patients selected with IDC in New York Heart Association functional class II to III heart failure and with a LV ejection fraction of < or = 40%. Left ventricular performance and dimensions were assessed using echocardiography (n = 161) and radionuclide ventriculography (n = 169). The frequency of ACE gene ID alleles was not different in the study versus non-age-matched (n = 171; odds ratio 0.94) and age-matched (n = 106, odds ratio 0.88) control groups. Ejection fraction was found to be worse in patients with the DD genotype (echocardiography, DD = 23.5 +/- 0.70, ID + II = 26.8 +/- 0.8, p = 0.009; ventriculography, DD = 21.7 +/- 0.9, ID + II = 25.3 +/- 0.8, p = 0.003). LV end-systolic and end-diastolic diameters were increased in patients with the DD genotype. Multifactor regression analysis showed the ACE genotype to be an independent predictor of both ejection fraction (echocardiography, p <0.02; ventriculography, p <0.03) and end-diastolic diameter (p <0.02). In conclusion, the results of this study indicate that the DD genotype of the ACE gene is independently associated with both a reduced LV systolic performance and an increased LV cavity size in patients with IDC.

Aged↗
PubMed1999

Comparison of acebutolol with and without hydrochlorothiazide versus carvedilol with and without hydrochlorothiazide in black patients with mild to moderate systemic hypertension.

In the present study, we assessed the antihypertensive efficacy of acebutolol 200 mg versus carvedilol 25 mg once daily, given as monotherapy for 3 months to 40 black patients (20 patients in each group, mean age 53+/-10 years, 24 women) with mean blood pressure (BP) during the day >90 and <110 mm Hg. Patients in whom blood pressure could not be controlled took medication, which was increased at 3-month intervals as follows: step 2, acebutolol 200 mg or carvedilol 25 mg plus hydrochlorothiazide 12.5 mg once daily; step 3, acebutolol 400 mg or carvedilol 50 mg plus hydrochlorothiazide 25 mg once daily. Overall, significant but modest BP reduction was achieved with both beta blockers at 3 months. In the acebutolol group, 24-hour BP decreased from 142+/-15/94+/-7 mm Hg to 138+/-16/89+/-8 mm Hg (p<0.005 for diastolic BP at 3 months vs baseline). Mean day BP decreased from 145+/-15/98+/-5 mm Hg to 140+/-14/93+/-7 mm Hg (p<0.05 for systolic BP and p<0.0005 for diastolic BP at 3 months vs. baseline). In the carvedilol group, 24-hour BP decreased from 145+/-11/93+/-6 to 138+/-16/87+/-9 mm Hg (p<0.05 for systolic BP and p<0.005 for diastolic BP at 3 months vs baseline). Mean day BP decreased from 149+/-10/99+/-5 to 141+/-16/91+/-87 mm Hg (p<0.05 for systolic BP and p<0.0005 for diastolic BP at 3 months vs baseline). At 12 months, most patients required combination therapy to achieve BP control. The control (mean day diastolic BP <90 mm Hg) and response (mean day diastolic BP decrease > or =10 mm Hg) rates at 12 months were 59% and 82% in the acebutolol and 78% and 78% in the carvedilol groups, respectively. In conclusion, acebutolol or carvedilol in combination with hydrochlorothiazide, rather than acebutolol or carvedilol alone, should be considered as first-line antihypertensive therapy in black patients with mild to moderate hypertension.

Acebutolol↗
PubMed1999

Jelly beans as an alternative to a fifty-gram glucose beverage for gestational diabetes screening.

OBJECTIVE: This study tested the hypothesis that a standardized dose of jelly beans could be used as an alternative sugar source to the 50-g glucose beverage to screen for gestational diabetes mellitus. STUDY DESIGN: One hundred sixty pregnant women at 24 to 28 weeks' gestation were recruited for a prospective study to compare 2 sugar sources for serum glucose response, side effects, preference, and ability to detect gestational diabetes mellitus. Patients were randomly assigned to consume 50-g glucose beverage or 28 jelly beans (50 g simple carbohydrate). Serum glucose values were determined 1 hour later. The test was later repeated with the other sugar source. Finally, a 100-g 3-hour oral glucose tolerance test was performed. Participants completed a questionnaire recording subjective outcome variables. American Diabetes Association criteria were used to interpret all test results. RESULTS: Among 136 participants completing the study no significant differences were found between 1-hour serum glucose values (116.5 +/- 27 mg/dL with 50-g glucose beverage, 116.9 +/- 23.6 mg/dL with jelly beans; P =.84), frequency of discrepant results (P =.47), sensitivity, specificity, or predictive value. Jelly beans yielded fewer side effects (38% with 50-g glucose beverage, 20% with jelly beans; P <.001) and were preferred by 76% of participants (P <.001). Five cases (3.7% incidence) of gestational diabetes mellitus were diagnosed, 3 with 50-g glucose beverage alone, 1 with jelly beans alone, and 1 with both sugar sources. CONCLUSIONS: Jelly beans may be used as an alternative to the 50-g glucose beverage as a sugar source for gestational diabetes mellitus screening. The 2 sources provoke similar serum glucose responses. Patients report fewer side effects after a jelly bean challenge than after a 50-g glucose beverage challenge.

Adolescent↗