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1.
J Pediatr Endocrinol Metab ; 34(2): 187-193, 2021 Feb 23.
Article in English | MEDLINE | ID: mdl-33544546

ABSTRACT

OBJECTIVE: We analyzed the impact of geographic distance from the clinic on adherence to recommended clinic visits and diabetes control among patients with type 1 diabetes (T1D) seen in a pediatric endocrinology clinic serving a rural region in eastern North Carolina. METHODS: We retrospectively included patients with T1D age ≤20 years seen in our clinic during 2017. Outcomes were tracked until June 2018. Distance from the clinic was determined according to the zone improvement plan (ZIP) code of patient address. Visit adherence was defined based on the number of attended visits during the study period, aiming for 1 every 3 months. Glycated hemoglobin (HbA1c) was measured at the first and last visits during the review period. RESULTS: The analysis included 368 patients, of whom 218 (59%) completed at least 1 visit every 3 months. The median HbA1c was 9.1 (interquartile range [IQR]: 8.0, 10.3) at the initial visit, and 9.3 (IQR: 8.0, 11.1) at the final visit. Median distance from the clinic was 56 km (IQR: 35, 86). On multivariable logistic regression, greater distance from the clinic was associated with lower odds of visit adherence (odds ratio per 10 km: 0.93; 95% confidence interval: 0.87, 0.99; p=0.030). Neither distance to the clinic nor clinic visit adherence were associated with HbA1c. CONCLUSIONS: Patients living further away from the clinic were less likely to adhere to the recommended visit schedule, but distance was not correlated with HbA1c levels. Further work is needed to assist families living far from the clinic with adhering to recommended visits.


Subject(s)
Ambulatory Care Facilities/standards , Biomarkers/blood , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 2/therapy , Endocrinology/standards , Health Services Accessibility/statistics & numerical data , Patient Compliance/statistics & numerical data , Adolescent , Adult , Blood Glucose/analysis , Child , Child, Preschool , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Female , Follow-Up Studies , Glycated Hemoglobin/analysis , Humans , Infant , Infant, Newborn , Male , Prognosis , Retrospective Studies , Rural Population , Young Adult
2.
Anaesthesia ; 74(12): 1619, 2019 12.
Article in English | MEDLINE | ID: mdl-31681998
3.
Leukemia ; 32(3): 663-674, 2018 03.
Article in English | MEDLINE | ID: mdl-28690315

ABSTRACT

Anthracyclines have been a cornerstone in the cure of diffuse large B-cell lymphoma (DLBCL) and other hematological cancers. The ability of anthracyclines to eliminate DLBCL depends on the presence of topoisomerase-II-alpha (TopIIA), a DNA repair enzyme complex. We identified nucleolin as a novel binding partner of TopIIA. Abrogation of nucleolin sensitized DLBCL cells to TopIIA targeting agents (doxorubicin/etoposide). Silencing nucleolin and challenging DLBCL cells with doxorubicin enhanced the phosphorylation of H2AX (γH2AX-marker of DNA damage) and allowed DNA fragmentation. Reconstitution of nucleolin expression in nucleolin-knockdown DLBCL cells prevented TopIIA targeting agent-induced apoptosis. Nucleolin binding to TopIIA was mapped to RNA-binding domain 3 of nucleolin, and this interaction was essential for blocking DNA damage and apoptosis. Nucleolin silencing decreased TopIIA decatenation activity, but enhanced formation of TopIIA-DNA cleavable complexes in the presence of etoposide. Moreover, combining nucleolin inhibitors: aptamer AS1411 or nucant N6L with doxorubicin reduced DLBCL cell survival. These findings are of clinical importance because low nucleolin levels versus high nucleolin levels in DLBCL predicted 90-month estimated survival of 70% versus 12% (P<0.0001) of patients treated with R-CHOP-based therapy.


Subject(s)
Antineoplastic Agents/pharmacology , Lymphoma, Large B-Cell, Diffuse/metabolism , Phosphoproteins/antagonists & inhibitors , RNA-Binding Proteins/antagonists & inhibitors , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , DNA Damage , DNA Topoisomerases, Type II/metabolism , Female , Gene Expression , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/mortality , Male , Molecular Targeted Therapy , Phosphoproteins/genetics , Phosphoproteins/metabolism , Poly-ADP-Ribose Binding Proteins/antagonists & inhibitors , Poly-ADP-Ribose Binding Proteins/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Nucleolin
4.
Epidemiol Infect ; 145(7): 1409-1417, 2017 05.
Article in English | MEDLINE | ID: mdl-28219463

ABSTRACT

We conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38-17·40), prior MRSA infection (OR 3·59; 95% CI 1·05-12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7-159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08-0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated.


Subject(s)
Methicillin-Resistant Staphylococcus aureus/physiology , Staphylococcal Infections/epidemiology , Adolescent , Adult , Aged , Anti-Bacterial Agents/pharmacology , Child , Child, Preschool , Clindamycin/therapeutic use , Female , Humans , Infant , Infant, Newborn , Male , Methicillin/pharmacology , Middle Aged , Pennsylvania/epidemiology , Prevalence , Prospective Studies , Risk Factors , Staphylococcal Infections/microbiology , Young Adult
5.
Leukemia ; 28(12): 2376-87, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24811343

ABSTRACT

Impaired Fas-mediated apoptosis is associated with poor clinical outcomes and cancer chemoresistance. Soluble Fas receptor (sFas), produced by skipping of exon 6, inhibits apoptosis by sequestering Fas ligand. Serum sFas is associated with poor prognosis of non-Hodgkin's lymphomas. We found that the alternative splicing of Fas in lymphomas is tightly regulated by a long-noncoding RNA corresponding to an antisense transcript of Fas (FAS-AS1). Levels of FAS-AS1 correlate inversely with production of sFas, and FAS-AS1 binding to the RBM5 inhibits RBM5-mediated exon 6 skipping. EZH2, often mutated or overexpressed in lymphomas, hyper-methylates the FAS-AS1 promoter and represses the FAS-AS1 expression. EZH2-mediated repression of FAS-AS1 promoter can be released by DZNeP (3-Deazaneplanocin A) or overcome by ectopic expression of FAS-AS1, both of which increase levels of FAS-AS1 and correspondingly decrease expression of sFas. Treatment with Bruton's tyrosine kinase inhibitor or EZH2 knockdown decreases the levels of EZH2, RBM5 and sFas, thereby enhancing Fas-mediated apoptosis. This is the first report showing functional regulation of Fas repression by its antisense RNA. Our results reveal new therapeutic targets in lymphomas and provide a rationale for the use of EZH2 inhibitors or ibrutinib in combination with chemotherapeutic agents that recruit Fas for effective cell killing.


Subject(s)
Lymphoma, B-Cell/blood , Lymphoma, B-Cell/genetics , RNA, Antisense/genetics , RNA, Long Noncoding/genetics , fas Receptor/blood , fas Receptor/genetics , Adenine/analogs & derivatives , Alternative Splicing , Apoptosis/genetics , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Line, Tumor , DNA Methylation , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Enhancer of Zeste Homolog 2 Protein , Fas Ligand Protein/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Gene Knockdown Techniques , Histones/metabolism , Humans , Introns , Lymphoma, B-Cell/metabolism , Models, Biological , Piperidines , Polycomb Repressive Complex 2/genetics , Polycomb Repressive Complex 2/metabolism , Protein Binding , Pyrazoles/pharmacology , Pyrimidines/pharmacology , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism
6.
Reprod Sci ; 21(11): 1362-9, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24604232

ABSTRACT

Resveratrol is a natural phytoestrogen with antiproliferative properties present in red wine, grapes, and berries. Published reports on the effects of resveratrol in human endometrial function are limited. The objective of this study was to investigate the expression of estrogen receptor α (ESR1), Ki-67 (a proliferative marker), aryl hydrocarbon receptor (AhR), and members of the cytochrome P450 superfamily of enzymes (CYP1A1 and CYP1B1) in an in vitro and vivo assay. Alkaline phosphatase assay of estrogenicity was used to compare estrogen activity of different concentrations of resveratrol to estradiol (E2) and diethylstilbestrol (DES), using Ishikawa cell culture. Immunohistochemical expression of ESR1 and Ki67, and reverse transcriptase polymerase chain reaction of AhR, CYP1A1, and CYP1B1 were analyzed from xenograft implants of human endometrial tissue in ovariectomized immunodeficient RAG-2-γ(c) mice, after 30 days of treatment with subcutaneous pellets of E2, E2 plus progesterone (P4), or E2 plus resveratrol (6, 30, or 60 mg) for 30 days. Compared to E2, resveratrol acted as an agonist and antagonist of estrogen in low and high concentrations, respectively, when combined with E2. Xenografts of human endometrial tissues in RAG-2 mice exhibited reduced expression of ESR1 and proliferative activity (Ki67) with 60 mg of resveratrol. This study suggests that resveratrol, at high doses, has the potential benefit to reduce proliferation of human endometrium through ESR1.


Subject(s)
Endometrium/drug effects , Phytoestrogens/pharmacology , Stilbenes/pharmacology , Wine , Alkaline Phosphatase/metabolism , Animals , Basic Helix-Loop-Helix Transcription Factors/drug effects , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Cell Proliferation/drug effects , Cytochrome P-450 CYP1A1/genetics , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 CYP1B1/genetics , Cytochrome P-450 CYP1B1/metabolism , DNA-Binding Proteins/deficiency , DNA-Binding Proteins/genetics , Diethylstilbestrol/pharmacology , Dose-Response Relationship, Drug , Endometrium/transplantation , Estradiol/pharmacology , Estrogen Receptor alpha/drug effects , Estrogen Receptor alpha/metabolism , Female , Heterografts , Humans , Ki-67 Antigen/metabolism , Mice, Inbred C57BL , Mice, Knockout , Ovariectomy , Receptors, Aryl Hydrocarbon/drug effects , Receptors, Aryl Hydrocarbon/genetics , Receptors, Aryl Hydrocarbon/metabolism , Resveratrol , Time Factors
7.
Diabetes Obes Metab ; 16(6): 510-8, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24298995

ABSTRACT

AIMS: To compare efficacy and safety of two, once-daily basal insulin formulations [insulin lispro protamine suspension (ILPS) vs. insulin glargine (glargine)] added to oral antihyperglycaemic medications (OAMs) and exenatide BID in suboptimally controlled type 2 diabetes (T2D) patients. METHODS: This 24-week, open-label, multicentre trial randomized patients to bedtime ILPS (n = 171) or glargine (n = 168). Non-inferiority of ILPS versus glargine was assessed by comparing the upper limit of 95% confidence intervals (CIs) for change in haemoglobin A1c (HbA1c) from baseline to week 24 (adjusted for baseline HbA1c) with non-inferiority margin 0.4%. RESULTS: Non-inferiority of ILPS versus glargine was demonstrated: least-squares mean between-treatment difference (ILPS minus glargine) (95% CI) was 0.22% (0.06, 0.38). Mean HbA1c reduction was less for ILPS- versus glargine-treated patients (-1.16 ± 0.84 vs. -1.40 ± 0.97%, p = 0.008). Endpoint HbA1c < 7.0% was achieved by 53.7% (ILPS) and 61.7% (glargine) (p = NS). Overall hypoglycaemia rates (p = NS) and severe hypoglycaemia incidence (p = NS) were similar. Nocturnal hypoglycaemia rate was higher in patients treated with ILPS versus glargine (p = 0.004). Weight gain was similar between groups (ILPS: 0.27 ± 3.38 kg; glargine: 0.66 ± 3.93 kg, p = NS). Endpoint total insulin doses were lower in patients treated with ILPS versus glargine (0.30 ± 0.17 vs. 0.37 ± 0.17 IU/kg/day, p < 0.001). CONCLUSIONS: ILPS was non-inferior to glargine for HbA1c change over 24 weeks, but was associated with less HbA1c reduction and more nocturnal hypoglycaemia. Treat-to-target basal insulin therapy improves glycaemic control and is associated with minimal weight gain when added to OAMs and exenatide BID for suboptimally controlled T2D.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hyperglycemia/drug therapy , Hypoglycemic Agents/administration & dosage , Insulin Lispro/administration & dosage , Insulin, Long-Acting/administration & dosage , Administration, Oral , Adolescent , Adult , Aged , Diabetes Mellitus, Type 2/metabolism , Female , Glycated Hemoglobin/metabolism , Humans , Hyperglycemia/metabolism , Hypoglycemia/chemically induced , Hypoglycemic Agents/adverse effects , Insulin Glargine , Insulin Lispro/adverse effects , Insulin, Long-Acting/adverse effects , Male , Middle Aged , Protamines/administration & dosage , Protamines/adverse effects , Treatment Outcome , Weight Gain , Young Adult
8.
Amino Acids ; 43(1): 5-12, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22327512

ABSTRACT

The main determinant of muscle carnosine (M-Carn) content is undoubtedly species, with, for example, aerobically trained female vegetarian athletes [with circa 13 mmol/kg dry muscle (dm)] having just 1/10th of that found in trained thoroughbred horses. Muscle fibre type is another key determinant, as type II fibres have a higher M-Carn or muscle histidine containing dipeptide (M-HCD) content than type I fibres. In vegetarians, M-Carn is limited by hepatic synthesis of ß-alanine, whereas in omnivores this is augmented by the hydrolysis of dietary supplied HCD's resulting in muscle levels two or more times higher. ß-alanine supplementation will increase M-Carn. The same increase in M-Carn occurs with administration of an equal molar quantity of carnosine as an alternative source of ß-alanine. Following the cessation of supplementation, M-Carn returns to pre-supplementation levels, with an estimated t1/2 of 5-9 weeks. Higher than normal M-Carn contents have been noted in some chronically weight-trained subjects, but it is unclear if this is due to the training per se, or secondary to changes in muscle fibre composition, an increase in ß-alanine intake or even anabolic steroid use. There is no measureable loss of M-Carn with acute exercise, although exercise-induced muscle damage may result in raised plasma concentrations in equines. Animal studies indicate effects of gender and age, but human studies lack sufficient control of the effects of diet and changes in muscle fibre composition.


Subject(s)
Carnosine/metabolism , Exercise/physiology , Muscle Fibers, Skeletal/metabolism , Muscle, Skeletal/metabolism , Carnosine/blood , Diet, Vegetarian , Female , Humans , Male , Muscle, Skeletal/chemistry , Sex Characteristics , beta-Alanine
9.
Indian J Med Res ; 128(4): 353-72, 2008 Oct.
Article in English | MEDLINE | ID: mdl-19106434

ABSTRACT

Hexavalent chromium (Cr(VI)), a commonly used industrial metal, is a well known human lung carcinogen. Epidemiology and animal studies suggest that the particulate Cr(VI) compounds, specifically the water insoluble compounds, are the more potent carcinogens; however, the carcinogenic mechanism remains unknown. Here we summarize recent Cr(VI)-induced human tumour, in vivo, cell culture and in vitro studies and put the data into context with three major paradigms of carcinogenesis: multistage carcinogenesis, genomic instability, and epigenetic modifications. Based on these studies, we propose a mechanism for chromate carcinogenesis that is primarily driven by the genomic instability paradigm.


Subject(s)
Carcinogens/toxicity , Chromium/toxicity , Animals , Carcinogenicity Tests , Humans
10.
Int J Sports Med ; 29(12): 952-8, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18548362

ABSTRACT

The effect of 30 days of beta-alanine supplementation (4.8 g per day) on resistance exercise performance and endocrine changes was examined in eight experienced resistance-trained men. An acute resistance exercise protocol consisting of 6 sets of 12 repetitions of the squat exercise at 70 % of one-repetition maximum (1-RM) with 1.5 minutes of rest between sets was performed before and after each supplemental period. Blood draws occurred at baseline (BL), immediate (IP), 15-minutes (15P) and 30-minutes (30P) postexercise for growth hormone, testosterone and cortisol concentrations. A 22 % (p < 0.05) difference in total number of repetitions performed at the end of 4 weeks of supplementation was seen between beta-alanine (BA) and placebo (PL), and Delta mean power was greater in BA (98.4 +/- 43.8 w) vs. PL (7.2 +/- 29.6 w). Growth hormone concentrations were elevated from BL at IP and 15P for both groups, while cortisol concentrations were greater than BL at all time points for both BA and PL. No group differences were noted. No change from BL was seen in testosterone concentrations for either group. Results indicate that four weeks of beta-alanine supplementation can significantly improve muscular endurance during resistance training in experienced resistance-trained athletes. However, these performance gains did not affect the acute endocrine response to the exercise stimulus.


Subject(s)
Adaptation, Physiological/physiology , Dietary Supplements , Exercise/physiology , Muscle Contraction/physiology , Muscle, Skeletal/physiology , beta-Alanine/therapeutic use , Adult , Cross-Over Studies , Double-Blind Method , Exercise Test , Growth Hormone/blood , Humans , Hydrocortisone/blood , Male , Muscle Strength/physiology , Sex Factors , Testosterone/blood , beta-Alanine/pharmacology
11.
J Reprod Immunol ; 77(2): 186-94, 2008 Apr.
Article in English | MEDLINE | ID: mdl-17884179

ABSTRACT

This study has evaluated the hypothesis that activity of the detoxifying enzyme butyrylcholinesterase (BuChE) correlates with levels of serum anti-cardiolipin antibodies (ACA) and T lymphocytes in peripheral blood of women experiencing recurrent spontaneous abortion (RSA). Peripheral venous blood from 16 non-pregnant, RSA-afflicted women and 8 healthy non-pregnant women was analyzed for frequency of T lymphocyte subpopulations by two-color flow cytometry and for serum BuChE using butyrylthiocholine iodide/spectrophotometry. RSA-afflicted women with high serum ACA, but not those with normal ACA levels, exhibited significantly increased percentages of CD4+CD25+ cells (p<0.01) and CD4+HLA-DR+ cells (p<0.05) relative to healthy women. CD4+CD25+(high) cells were significantly lower (p<0.05), while CD4+CD25+(low) cells were significantly higher (p<0.01), in women with elevated ACA compared to healthy women and to RSA women with normal ACA. Relative to healthy, non-pregnant subjects, serum BuChE activity in RSA patients was elevated, both for those with normal ACA (p<0.001) and elevated ACA levels (p<0.01). Among healthy controls, a significant positive correlation was observed between frequency of CD3+NK cells and BuChE activity (p<0.01), but not for RSA-afflicted subjects. A positive correlation between BuChE activity and frequency of CD4+CD25+ cells, as well as CD4+CD25+(high) cells, was observed in the RSA-afflicted subject group with elevated ACA (p<0.05), which may be related to induction of BuChE by toxic metabolites resulting from pathogenic T cell activity. It is concluded that, among RSA patients, high serum ACA correlates with elevated levels of activated T cells and reduced CD4+CD25+(high)/CD4+CD25+(low) cells in comparison to healthy women or those afflicted with RSA but with normal ACA. BuChE activity is observed to be elevated in RSA patients irrespective of serum ACA status.


Subject(s)
Abortion, Spontaneous/enzymology , Butyrylcholinesterase/blood , Lymphocyte Subsets/enzymology , Abortion, Spontaneous/blood , Adult , Antibodies, Anticardiolipin/blood , CD4-Positive T-Lymphocytes/enzymology , CD4-Positive T-Lymphocytes/pathology , Cell Separation , Female , Flow Cytometry , Humans , Interleukin-2 Receptor alpha Subunit , Kuwait , Lymphocyte Subsets/pathology , Pregnancy , T-Lymphocytes, Regulatory/enzymology , T-Lymphocytes, Regulatory/pathology
12.
Dis Esophagus ; 20(3): 202-5, 2007.
Article in English | MEDLINE | ID: mdl-17509115

ABSTRACT

While multiple instruments characterize upper gastrointestinal symptoms, a validated instrument devoted to the measurement of a spectrum of esophageal dysphagia attributes is not available. Therefore, we constructed and validated the Mayo Dysphagia Questionnaire (MDQ). The 27 items of the MDQ underwent content validity, feasibility, concurrent validity, reproducibility, internal consistency, and construct validity testing. To assess content validity, five esophageal subspecialty gastroenterologists reviewed the items to ensure inclusion of pertinent domains. Feasibility testing was done with eight outpatients who refined problematic items. To assess concurrent validity, 70 patient responses on the MDQ were compared to responses gathered in a structured patient-physician interview. A separate group of 70 outpatients completed the MDQ twice to assess the reproducibility of each item. A total of 148 patients participated in the validation process (78 [53%] men; mean age 62). On average, the MDQ took 6 minutes to complete. A single item (odynophagia) tested poorly with a kappa value of <0.4. Otherwise, the majority of concurrent validity kappa values were in the good to excellent range with a mean of 0.63 (95% CI 0.22-0.89). The majority of reproducibility kappa values were also in the good to excellent range with a median kappa value of 0.76 (interquartile range: 0.67-0.81). Cronbach's alpha values were excellent in the range of 0.86-0.88. Spearman rank correlation coefficients to assess construct validity were also excellent in the range of 0.87-0.98. Thus, the MDQ is a concise instrument that demonstrates overall excellent concurrent validity, reproducibility, internal consistency, and construct validity for the features of esophageal dysphagia.


Subject(s)
Deglutition Disorders/diagnosis , Surveys and Questionnaires , Aged , Aged, 80 and over , Deglutition Disorders/complications , Deglutition Disorders/physiopathology , Feasibility Studies , Female , Humans , Male , Middle Aged , Pain/etiology , Reproducibility of Results , Severity of Illness Index
13.
Dis Esophagus ; 20(2): 83-8, 2007.
Article in English | MEDLINE | ID: mdl-17439589

ABSTRACT

The diagnosis of gastroesophageal reflux is sometimes challenging, especially when symptoms are unresponsive to high-dose acid suppression. With the advent of new technology it is possible to detect and quantify nonacid or weakly acidic reflux. Multichannel intraluminal impedance (MII), introduced over 10 years ago, is gaining popularity as a reflux detection tool. The ability to detect nonacid or weakly acidic reflux events, aerophagia, and to discern true reflux events from swallows could make it more a powerful tool than pH detection alone. This is a review of the role of MII as it pertains to the diagnosis of GERD and related disorders. Studies done on normal subjects and in GERD reveal that nonacid or weakly acidic reflux occurs frequently. Several studies have been published that document types and frequency or reflux episodes comparing pH to MII. pH electrodes fail to detect the majority of nonacid or weakly acidic reflux events. MII has revealed nonacid reflux to be less common in untreated GERD subjects than in normal subjects. GERD subjects have greater degrees of liquid-type reflux events compared to normal subjects who have more gas-type reflux events. In treated GERD subjects and normal subjects, proton pump inhibitors do not seem to decrease the amount of reflux but render the reflux nonacid or weakly acidic in nature. Recently work evaluating atypical symptoms of GERD with MII has been published.


Subject(s)
Electric Impedance , Gastroesophageal Reflux/diagnosis , Anti-Ulcer Agents/therapeutic use , Esophageal pH Monitoring , Gastroesophageal Reflux/drug therapy , Humans , Postprandial Period , Reproducibility of Results
14.
Amino Acids ; 32(2): 225-33, 2007 Feb.
Article in English | MEDLINE | ID: mdl-16868650

ABSTRACT

Muscle carnosine synthesis is limited by the availability of beta-alanine. Thirteen male subjects were supplemented with beta-alanine (CarnoSyn) for 4 wks, 8 of these for 10 wks. A biopsy of the vastus lateralis was obtained from 6 of the 8 at 0, 4 and 10 wks. Subjects undertook a cycle capacity test to determine total work done (TWD) at 110% (CCT(110%)) of their maximum power (Wmax). Twelve matched subjects received a placebo. Eleven of these completed the CCT(110%) at 0 and 4 wks, and 8, 10 wks. Muscle biopsies were obtained from 5 of the 8 and one additional subject. Muscle carnosine was significantly increased by +58.8% and +80.1% after 4 and 10 wks beta-alanine supplementation. Carnosine, initially 1.71 times higher in type IIa fibres, increased equally in both type I and IIa fibres. No increase was seen in control subjects. Taurine was unchanged by 10 wks of supplementation. 4 wks beta-alanine supplementation resulted in a significant increase in TWD (+13.0%); with a further +3.2% increase at 10 wks. TWD was unchanged at 4 and 10 wks in the control subjects. The increase in TWD with supplementation followed the increase in muscle carnosine.


Subject(s)
Carnosine/biosynthesis , Dietary Supplements , Muscle, Skeletal/metabolism , beta-Alanine/administration & dosage , beta-Alanine/pharmacology , Adult , Biopsy , Carnosine/metabolism , Drug Administration Schedule , Exercise Test , Humans , Hydrogen-Ion Concentration , Male , Models, Biological , Muscle, Skeletal/drug effects , Protons , Taurine/metabolism , Time Factors
15.
Mar Environ Res ; 62 Suppl: S20-4, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16698075

ABSTRACT

The North Atlantic right whale (NARW) is one of the most endangered great whales. The NARW population consists of only about 300 individuals and is reproducing at an insufficient rate. There is growing concern about the potential effects of environmental contaminants on the reproductive and overall health of NARW. High contaminant burdens can accumulate in tissues of great whales but toxicological studies of their effects are limited due to legal, logistical and ethical restrictions and specific in vitro models are critically needed. Cell lines from NARW skin and internal organs were previously created in our laboratory. In this study, skin, testis and lung primary fibroblast cell lines were exposed to benzo[a]pyrene (BP) as part of a multi-chemical toxicity testing project in NARW. Cells were exposed for 24-72 h to 10 nM-10 microM BP dissolved in dimethylsulfoxide. Cytotoxicity was measured with a clonogenic assay using standard methods. Some cytotoxicity was observed after 24 h, the highest concentration (10 microM BP) resulting in 77, 74 and 51 percent relative survival in testis, skin and lung cells, respectively, and indicating a higher cytotoxicity in the lung (p < 0.05). After 48 and 72-h exposure, 10 microM BP resulted in 24 and 3, 74 and 27, and 42 and 23 percent relative survival in testis, skin and lung cells, respectively. Cytotoxicity significantly increased with exposure time in all three tissues (p < 0.05 for skin and p < 0.01 for lung and testis), suggesting metabolic activation of BP in the three organs. Fibroblast cytotoxicity observed in the testis was higher than that observed either in the skin or lung after 48 h (p < 0.01) and was close to 100% after 72 h, warranting further investigation of the potential effects of PAHs on reproductive health.


Subject(s)
Benzo(a)pyrene/toxicity , Water Pollutants, Chemical/toxicity , Whales , Animals , Cell Line , Colony-Forming Units Assay , Fibroblasts/cytology , Fibroblasts/drug effects , Lung/cytology , Lung/drug effects , Male , Skin/cytology , Skin/drug effects , Survival Analysis , Testis/cytology , Testis/drug effects , Time Factors
16.
Amino Acids ; 30(3): 279-89, 2006 May.
Article in English | MEDLINE | ID: mdl-16554972

ABSTRACT

Beta-alanine in blood-plasma when administered as A) histidine dipeptides (equivalent to 40 mg . kg(-1) bwt of beta-alanine) in chicken broth, or B) 10, C) 20 and D) 40 mg . kg(-1) bwt beta-alanine (CarnoSyn, NAI, USA), peaked at 428 +/- SE 66, 47 +/- 13, 374 +/- 68 and 833 +/- 43 microM. Concentrations regained baseline at 2 h. Carnosine was not detected in plasma with A) although traces of this and anserine were found in urine. Loss of beta-alanine in urine with B) to D) was <5%. Plasma taurine was increased by beta-alanine ingestion but this did not result in any increased loss via urine. Pharmacodynamics were further investigated with 3 x B) per day given for 15 d. Dietary supplementation with I) 3.2 and II) 6.4 g . d(-1) beta-alanine (as multiple doses of 400 or 800 mg) or III) L-carnosine (isomolar to II) for 4 w resulted in significant increases in muscle carnosine estimated at 42.1, 64.2 and 65.8%.


Subject(s)
Carnosine/metabolism , Dietary Supplements , Quadriceps Muscle/metabolism , beta-Alanine/pharmacokinetics , Adult , Aged , Aged, 80 and over , Dipeptides/administration & dosage , Dipeptides/pharmacokinetics , Humans , Male , Taurine/blood , Taurine/urine , beta-Alanine/administration & dosage
17.
Otolaryngol Head Neck Surg ; 134(1): 73-80, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16399184

ABSTRACT

OBJECTIVE: To develop and validate a questionnaire for supraesophageal manifestations of reflux (SER) that will facilitate its study in clinical and research settings. STUDY DESIGN: The Supraesophageal Reflux Questionnaire (SERQ) and previously validated Reflux Symptom Index (RSI) were subjected to multiple types of validity testing, including content validity, concurrent validity, reproducibility, and predictive validity. RESULTS: The concurrent validity and reproducibility of both instruments was good to excellent for most items tested. The predictive validity of the SERQ was superior to the RSI when it included the covariates of history of sinusitis, use of over-the-counter antacid medications, age, gender, and body mass index. CONCLUSIONS: The SERQ will serve as both a useful clinical and research tool by offering not only SER symptom information, like the RSI, but also information about the patient's medical history and medication usage that will facilitate use of the SERQ in research protocols. EBM RATING: B-2b.


Subject(s)
Gastroesophageal Reflux/complications , Health Status Indicators , Surveys and Questionnaires , Antacids/administration & dosage , Anti-Ulcer Agents/administration & dosage , Gastroesophageal Reflux/drug therapy , Gastroesophageal Reflux/psychology , Humans , Medical History Taking , Patient Acceptance of Health Care , Predictive Value of Tests , ROC Curve , Reproducibility of Results
18.
Aliment Pharmacol Ther ; 22(10): 1023-31, 2005 Nov 15.
Article in English | MEDLINE | ID: mdl-16268978

ABSTRACT

BACKGROUND: Non-cardiac chest pain is a common and expensive condition. Risk factors for non-cardiac chest pain are poorly understood and lack description in the USA community. AIM: To explore risk factors and health-seeking behaviour in non-cardiac chest pain in a USA community. METHODS: Olmsted County, MN subjects who reported at least monthly or severe chest pain in response to a validated questionnaire were compared with controls. All the Mayo Clinic medical records were reviewed; those with cardiac disease or relevant organic conditions were excluded. RESULTS: Of 2118 eligible subjects, 1524 (72%) returned a questionnaire, 389 subjects (26%) reported any chest pain and 186 (12.2%) at least monthly or severe chest pain. Of these, 62 were excluded for a cardiac diagnosis or another organic cause. Thus, 124 subjects (9.1%, 95% CI: 7.6-10.8%) reported at least monthly or severe non-cardiac chest pain, of which 65 (52.4%) had frequent reflux symptoms. Independent risk factors for non-cardiac chest pain were obesity (OR 3.0, 95% CI: 1.64-5.50), family history of reflux (OR 2.8, 95% CI: 1.73-4.32), previous cigarette use (OR 2.0, 95% CI: 1.27-3.18), aspirin use (OR 1.5, 95% CI: 1.00-2.31) and use of antiarthritis medicines (OR 2.0, 95% CI: 1.27-3.16). Compared with subjects with non-cardiac chest pain and associated gastro-oesophageal reflux symptoms, subjects with non-cardiac chest pain without associated gastro-oesophageal reflux symptoms were less likely to have a family history of reflux, more likely to be younger, and less likely to be obese. Compared with controls, subjects with non-cardiac chest pain without gastro-oesophageal reflux symptoms were younger (OR 0.97, 95% CI: 0.95-0.99), reported higher somatic symptom scores (OR 1.1, 95% CI: 1.08-1.73) and were more likely to be obese (OR 2.6, 95% CI: 1.15-5.93). CONCLUSIONS: Recurrent or severe non-cardiac chest pain is common in the community. Half of the people with significant non-cardiac chest pain have frequent reflux symptoms, thus, risk factors for non-cardiac chest pain are similar to risk factors for gastro-oesophageal reflux disease. People with non-cardiac chest pain without reflux symptoms have a slightly different risk factor profile.


Subject(s)
Chest Pain/epidemiology , Adult , Aged , Chest Pain/etiology , Female , Gastroesophageal Reflux/epidemiology , Health Behavior , Humans , Logistic Models , Maine/epidemiology , Male , Middle Aged , Risk Factors , Surveys and Questionnaires
19.
J Anim Sci ; 83(12): 2869-75, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16282626

ABSTRACT

The objectives of this study were to evaluate whether instructions can help consumers properly prepare top sirloin steaks and to evaluate the use of calcium chloride injection to decrease the sensitivity of top sirloin steaks to degree of doneness, thereby improving customer satisfaction ratings. An in-home study evaluated top sirloin steaks (gluteus medius) as influenced by calcium chloride injection (injected vs. noninjected), consumer segment (beef loyalists = heavy consumers of beef, budget rotators = cost-driven and split meat consumption between beef and chicken, and variety rotators = higher incomes and education and split meat consumption among beef, poultry, and other foods), degree of doneness, cooking method, and instructions (given vs. not given). Consumers evaluated overall like, tenderness, juiciness, flavor like, and flavor amount using 10-point scales. Beef loyalists consistently rated steaks higher for overall like, juiciness, and flavor when instructions were provided (P < 0.05) and rated top sirloin steaks higher for overall like and tenderness when given instructions for grilling (P < 0.05). Budget rotators and variety rotators rated steaks differently among cooking methods (P < 0.05). Correlation and stepwise regression analyses indicated that flavor like was the most highly correlated with overall like, followed by tenderness, flavor amount, and juiciness. Calcium chloride injection had no effect on consumers' likes or dislikes or on tenderness (P < 0.05). For top sirloin steaks, it was likely that preparation played a major role in consumer satisfaction, and beef loyalists benefited the most from providing cooking instructions.


Subject(s)
Calcium Chloride , Consumer Behavior , Cooking , Meat/standards , Animals , Cattle
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