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Objectives: Commercial gambling markets have undergone unprecedented expansion and diversification in territories across Sub-Saharan Africa (SSA). This gambling boom has popularised the uptake of gambling products in existing circuits of popular culture, sport and leisure and raised concerns about the extent to which state legislation is equipped to regulate the differentiated impacts of gambling on public health., Study Design: Comparative policy analysis., Methods: This article provides a systematic mapping of the regulatory environment pertaining to gambling across SSA. The review was conducted by obtaining and triangulating data from a desk review of online materials, consultation with regulatory bodies in each territory and the VIXIO Gambling Compliance database., Results: Gambling is legally regulated in 41 of 49 (83.6%) SSA countries, prohibited in 7 (14.3%) and is not legislated for in 1 (2.0%). Of those countries that regulate gambling, 25 (61.0%) countries had dedicated regulators and 16 (39.0%) countries regulated via a government department. Only 2 of 41 (4.9%) countries have published annual reports continuously since the formation of regulatory bodies, and 3 (7.3%) countries have published an incomplete series of reports since the formation. In 36 (87.8%) countries, no reports were published. Enforcement activities were documented by all five regulators that published reports., Conclusion: The review uncovered a lack of coherence in regulatory measures and the need for more transparent public reporting across SSA territories. There are also variations in regulating online products and marketing, with most countries lacking apt guidelines for the digital age. Our findings suggest an urgent need to address the regulatory void surrounding online forms of gambling and the promotion of gambling products. This underlines the importance of a public health approach to protect against an increase in gambling-related harms., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The sourcing of novel bioactive compounds from bioresources has become a sustainability priority for several industrial sectors. Reliable methods are hence needed for the screening and identification of desired molecules in complex extracts. As such, phenolic compounds have attracted increasing interests due to their antioxidant potential. Here, a HPLC-UV based method was developed for the determination of phenolic compounds using a monolithic column. This allowed the separation of 23 phenolic compounds within 11 min. The method was ground proofed in terms of chromatographic parameters and applied to identify polyphenols in extracts of blueberries, basil and marine microalgae. The dominant polyphenols in blueberries and basil were chlorogenic acid (26.0 mg. kg -1 ) and kaempferol (61.4 mg. kg -1 ), respectively, while the microalgae used only contained trace amounts of polyphenols. This study demonstrates the value of our new HPLC method to rapidly screen extracts and identify polyphenols from biological matrices., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: Online sports gambling has become an increasingly popular feature of male youth culture and fandom in recent decades. Fuelled by advances in mobile app technologies and the liberalisation of state regulations on advertising, this 'gamblification' of sport has given rise to a global industry promoting gambling as a knowledge-based, risk-free leisure activity. This study examined how the growth of online sports gambling has impacted on gambling behaviours among young adult men in the UK and how it may pose new risks concerning the normalisation of gambling behaviours., Study Design: The study used a multiphased qualitative research design., Methods: The study was conducted with 32 adult men (aged 18-35 years) across two sites, Derry, Northern Ireland, and Bristol, England. It comprised three phases of data collection: participatory focus groups, a 30-day gambling diary and semistructured interviews., Results: Four main themes emerged. First, data suggest that gambling has become a normalised aspect of sports fandom for male youth demographics, many of whom view the casual wagering of money as vital to their enjoyment of sport. Second, the perceived 'facelessness' of sports gambling platforms via mobile app technologies was reported to increase inclination to engage in sports betting. Third, 'free bet' incentives and in-play promotions play a significant role as a mechanism of inducement towards sports gambling practices. Fourth was the potential role of online sports gambling as a gateway to gambling-related harms, including financial precarity, indebtedness, mortgage defaults, family breakdown, loss of employment and mental health struggles., Conclusion: Online sports gambling has significant public health implications, particularly for male youth demographics. Policymakers in the UK should consider stronger regulation of gambling-related advertising and sponsorship in sport, independent risk assessments of sports gambling products and a commitment to safeguarding youth demographics from gambling-related harm in a digital age., (Copyright © 2020 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

We describe the development of an electrochemical sensor for early detection of biofilm using Candida albicans. The electrochemical sensor used the ability of biofilms to accept electrons from redox mediators relative to the number of metabolically active cells present. Cyclic voltammetry and differential pulse voltammetry techniques were used to monitor the redox reaction of K(3)Fe(CN)(6) at porous reticulated vitreous carbon (RVC) (238.7 cm(2)) working electrodes versus Ag/AgCl reference. A shift in the peak potential occurred after 12 h of film growth, which is attributed to the presence of C. albicans. Moreover, the intensity of the ferricyanide reduction peak first increased as C. albicans deposited onto the porous electrodes at various growth times. The peak current subsequently decreased at extended periods of growth of 48 h. The reduction in peak current was attributed to the biofilm reaching its maximum growth thickness, which correlated with the maximum number of metabolically active cells. The observed diffusion coefficients for the bare RVC and biofilm-coated electrodes were 2.2 × 10(-3) and 7.0 × 10(-6) cm(2)/s, respectively. The increase in diffusivity from the bare electrode to the biofilm-coated electrode indicated some enhancement of electron transfer mediated by the biofilm to the porous electrode. Verification of the growth of biofilm was achieved using scanning electron microcopy and laser scanning confocal imaging microscopy. Validation with conventional plating techniques confirmed that the correlation (R(2) = 0.9392) could be achieved between the electrochemical sensors data and colony-forming units., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Representatives of emergency medicine (EM) were asked to develop a consensus report that provided a review of the past and potential future effects of duty hour requirements for EM residency training. In addition to the restrictions made in 2003 by the Accreditation Council for Graduate Medical Education, the potential effects of the 2008 Institute of Medicine (IOM) report on resident duty hours were postulated., Discussion: The elements highlighted include patient safety, resident wellness, and the resident training experience. Many of the changes and recommendations did not affect EM as significantly as other specialties. Current training standards in EM have already emphasized patient safety by requiring continuous onsite supervision of residents. Resident fatigue has been addressed with restrictions of shift lengths and limitation of consecutive days worked., Conclusion: One recommendation from the IOM was a required 5-h rest period for residents on call. Emergency department (ED) patient safety becomes an important concern with the decrease in the availability and in the patient load of a resident consultant that may result from this recommendation. Of greater concern is the already observed slower throughput time for admitted patients waiting for resident care, which will increase ED crowding and decrease patient safety in academic institutions. A balance between being overly prescriptive with duty hour restrictions and trying to improve resident wellness was recommended. Discussion is included regarding the appropriate length of EM training programs if clinical experiences were limited by new duty hour regulations. Finally, this report presents a review of the financing issues associated with any changes., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Lipoproteins may contribute to diabetic nephropathy. Nuclear magnetic resonance (NMR) can quantify subclasses and mean particle size of very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL), and LDL particle concentration. The relationship between detailed lipoprotein analyses and diabetic nephropathy is of interest., Methods: In a cross-sectional study, lipoproteins from 428 women and 540 men from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort were characterized by conventional lipid enzymology, NMR, apolipoprotein levels, and LDL oxidizibility. Linear regression was performed for each lipoprotein parameter versus log albumin excretion rate (AER), with and without covariates for age, diabetes duration, HbA1c, hypertension, body mass index, waist-hip ratio, and DCCT treatment group. Significance was taken at P < 0.05., Results: By multivariate analysis, conventional profile, total triglycerides, total- and LDL cholesterol, but not HDL cholesterol, were associated with AER. NMR-determined large, medium, and small VLDL were associated with AER in both genders (except large VLDL in women), and intermediate density lipoprotein (IDL) was associated with AER (men only). LDL particle concentration and ApoB were positively associated with AER (in men and in the total cohort), and there was a borderline inverse association between LDL diameter and AER in men. Small HDL was positively associated with AER and a borderline negative association was found for large HDL. No associations were found with ApoA1, Lp(a), or LDL oxidizibility., Conclusion: Potentially atherogenic lipoprotein profiles are associated with renal dysfunction in type 1 diabetes and further details are gained from NMR analysis. Longitudinal studies are needed to determine if dyslipoproteinemia can predict patients at risk of nephropathy, or if lipoprotein-related interventions retard nephropathy.

The objective of this study was to determine the efficacy of the rectal administration of dextrose in raising the serum glucose in a hypoglycemic rat model. A randomized, prospective, controlled experimental study was performed using 18-h fasted, acutely anesthetized Harlan Sprague-Dawley rats made hypoglycemic by the intravenous infusion of insulin at 3 U/kg/h for 2 h. At 1 h into the infusion, study rats received 1, 2, or 3 g/kg of 50% dextrose solution infused into the rectum using a balloon tipped catheter. Control animals received an equivolume, equi-osmolar (as compared to the 3 g/kg dose) amount of polyethylene glycol (PEG)-400 by rectum. Blood glucose (BG) measurements were made using blood obtained from the portal vein and a femoral artery. Intravenous insulin administered at 3 U/kg/h consistently produced BG levels 60% of baseline at 60 min and 80% of baseline at 120 min. BG levels in portal and arterial circulation increased after rectal dextrose. In general, portal venous values were greater than arterial after rectal dextrose. The greatest increase was seen 30 min after dextrose by rectum in animals receiving 3 g/kg. A 50% dextrose administered by rectum in hypoglycemic rats is absorbed in quantities sufficient to raise BG in the arterial and portal circulation.

Background: Involved or implicated in a wide spectrum of diseases, trypsin-like serine proteases comprise well studied drug targets and anti-targets that can be subdivided into two major classes. In one class there is a serine at position 190 at the S1 site, as in urokinase type plasminogen activator (urokinase or uPA) and factor VIIa, and in the other there is an alanine at 190, as in tissue type plasminogen activator (tPA) and factor Xa. A hydrogen bond unique to Ser190 protease-arylamidine complexes between O gamma(Ser190) and the inhibitor amidine confers an intrinsic preference for such inhibitors toward Ser190 proteases over Ala190 counterparts., Results: Based on the structural differences between the S1 sites of Ser190 and Ala190 protease-arylamidine complexes, we amplified the selectivity of amidine inhibitors toward uPA and against tPA, by factors as high as 220-fold, by incorporating a halo group ortho to the amidine of a lead inhibitor scaffold. Comparison of K(i) values of such halo-substituted and parent inhibitors toward a panel of Ser190 and Ala190 proteases demonstrates pronounced selectivity of the halo analogs for Ser190 proteases over Ala190 counterparts. Crystal structures of Ser190 proteases, uPA and trypsin, and of an Ala190 counterpart, thrombin, bound by a set of ortho (halo, amidino) aryl inhibitors and of non-halo parents reveal the structural basis of the exquisite selectivity and validate the design principle., Conclusions: Remarkable selectivity enhancements of exceptionally small inhibitors are achieved toward the uPA target over the highly similar tPA anti-target through a single atom substitution on an otherwise relatively non-selective scaffold. Overall selectivities for uPA over tPA as high as 980-fold at physiological pH were realized. The increase in selectivity results from the displacement of a single bound water molecule common to the S1 site of both the uPA target and the tPA anti-target because of the ensuing deficit in hydrogen bonding of the arylamidine inhibitor when bound in the Ala190 protease anti-target.

Purpose: The purpose of this study was to assess the association between serum ferritin and death from all causes, cardiovascular diseases (CVD), CHD and myocardial infarction (MI). Positive body iron stores have been proposed as a risk factor for coronary heart disease (CHD). While most epidemiologic studies using serum ferritin and other measures of body iron stores have not found an association between iron and heart disease risk, the hypothesis remains controversial. As a result, we examined the relationship of serum ferritin, the principle blood measure of body iron stores, to risk of death in a cohort with a standardized exam and long follow-up., Methods: The baseline data for this prospective cohort study were collected in 1976-1980 as part of the second National Health and Nutrition Examination Study (NHANES II) with mortality follow-up using the National Death Index (NDI) through December 31, 1992. The analytic sample (n = 1604) consisted of 128 black men, 658 white men, 100 black women and 718 white women 45-74 years of age at baseline who, based on self-reported data, were free of coronary heart disease at baseline and had no missing data. The main outcome measures were the relative risk of death for persons with serum ferritin levels: <50 microg/L; or 100-199 microg/L; or > or =200 microg/L was compared to persons with serum ferritin levels of 50-99 microg/L adjusted for possible confounding using the Cox proportional hazards model., Results: Most of the deaths were among white men (n = 254) and women (n = 168). There were relatively few deaths among black men (n = 50) and too few in women (n = 23) to reliably model. The largest number of CVD (n = 119), CHD (n = 82), and MI (n = 49) deaths were in white men while there were 69 CVD, 45 CHD and 13 MI deaths in white women. Black men with a serum ferritin level of <50 microg/L had a significantly higher adjusted risk of death from all causes (RR = 3.1 with 95% confidence limits of 1.5-6.5). There were no other statistically significant associations for all causes mortality for the other three race/sex groups. Additionally, there were no statistically significant associations between serum ferritin and any of the cardiovascular endpoints for any of the groups. There was an apparent but nonsignificant u-shaped association between serum ferritin and all causes mortality in black men and between serum ferritin and CVD death in white women. However, in both cases very wide confidence limits preclude further interpretation., Conclusions: Overall, the results do not support the hypothesis that positive body iron stores, as measured by serum ferritin, are associated with an increased risk of CVD, CHD or MI death or between serum ferritin and all causes mortality. Most of the research to date with serum ferritin has been conducted in European men or in European American men. Our results are consistent with the primarily negative results for that race/sex group. More research is needed in women and minority groups, including an explanation of why such an association would exist in these groups but not in white men before an association can be established in them.

Purpose: To calculate for two measures of obesity, the Metropolitan Relative Weight (MRW) and body mass index (BMI), the value at which minimum mortality occurs. This was done to retest the hypothesis, in the Framingham Heart Study data, that the association between obesity and mortality can be obscured by an interaction between the measure of obesity and smoking. In the original analysis of the Framingham data it was suggested that there was a U- or J-shaped relationship between MRW and death in smokers but a linear relationship in nonsmokers. The design and setting were those of the NHLBI Framingham Heart Study., Methods: The 5209 members of the Framingham Heart Study underwent a baseline examination in 1948-1952 (Exam 1) and they were reexamined at approximately two-year intervals over a 30-year period. The study included both men (n = 2336) and women (n = 2873) in the age range of 28 to 62 years. After excluding persons with missing baseline data, the analytic sample size was 5163. Additional analyses were conducted by deleting persons with cardiovascular disease (CVD) at baseline (n = 135), the sample used by the original paper by Garrison and colleagues, and persons who died within the first four years of follow-up (n = 62). The main outcome measures consisted of thirty-year survival through Exam 16, approximately in 1980, as influenced by MRW or BMI, age, and smoking status at baseline (Exam 1)., Results: We were able to show that the sample sizes of male nonsmokers were too small to test the hypothesis within age groups < 40 and 40-49 years. In men ages 50-62 there was a significant age-adjusted quadratic relationship between BMI or MRW, and risk of death. The estimated BMI at the minimum risk of death for smokers (24.5) and nonsmokers (23.8) were not statistically different. Identical results were found for MRW (minimum: smokers = 112.5, nonsmokers = 111.4). In men and women ages 28-62 there appeared to be a u- or j-shaped relationship between the 30-year crude mortality rate and MRW. After excluding persons with missing data, CVD at baseline, and persons who died within the first four years of follow-up, the age adjusted estimated BMI value at the minimum risk of death was nearly identical for men and women and for smokers and nonsmokers (Men: smokers = 22.8, nonsmokers = 22.8; Women: smokers = 22.9, nonsmokers = 23.3). Additionally, the estimates of the minimum were always below the mean. Identical results were found without deleting persons with CVD at baseline and deaths in the first four years of follow-up. Identical results were found for MRW., Conclusions: Reanalysis of the Framingham Heart Study data does not support the hypothesis that there is an interaction between smoking and measures of obesity. Moreover, the estimated BMI or MRW at the minimum risk of death was similar for men and women smokers and nonsmokers alike even after deleting prevalent cases of CVD and deaths within the first four years of follow-up.

Purpose: To examine the impact of relative weight on mortality in black and white men and women., Methods: Two representative national populations samples were used: the NHANES-I Epidemiologic Follow-up Study (NHEFS), and the National Health Interview Survey (NHIS). The principal analysis focused on 13,242 participants in the NHEFS and 114,954 in the NHIS. Minimum mortality was estimated from both categorical analysis and a logistic model., Results: Minimum mortality ranged from a body mass index (BMI) of 25 to 32 kg/m2. The model-estimated BMI of minimum mortality for NHEFS was 27.1 (24.8-29.4, 95% CI), 26.8 (24.7-28.9, 95% CI), 24.8 (23.8-25.9, 95% CI) and 24.3 (23.2-25.4, 95% CI); for black men, black women, white men and white women, respectively, whereas for NHIS the corresponding values were 30.2 (24.8-35.6, 95% CI) 26.4 (24.2-28.7, 95% CI), 27.1 (25.5-28.7, 95% CI), and 25.6 (24.2-27.0, 95% CI). In all groups the shape of the relative risk curve was virtually identical and a broad range of BMI values in the middle of the distribution was associated with low relative mortality risk. Averaging the results from both surveys, the observed BMI of minimum risk was 3.1 kg/m2 higher in black men and 1.5 kg/m2 higher in black women than in their white counterparts; when adjusted for covariates these differences were only of borderline statistical significance, however., Conclusions: Because of the wide range of BMI values associated with low risk, and the consistency of the point of the up-turn in risk, group specific definitions of optimal values do not appear to be warranted.

Accurate assessment of dietary behavior is central to the design, implementation, and evaluation of intervention programs aimed at behavior change, and use of an Eating Behaviors Questionnaire (EBQ) has been suggested for measuring dimensions of dietary fat behavior. The EBQ has proven useful in characterizing fat-related dietary patterns among middle-class, highly educated, highly motivated white women. To investigate the generalizability of the instrument, we provide findings from a community-based sample of 235 African-Americans in Maywood, Illinois, a middle-class working community outside Chicago. The sample consisted of 159 women and 76 men with an average age of 47.4 +/- 13.8 years for women and 48.1 +/- 12.1 years for men (mean +/- standard deviation; range, 18 to 87 years). The EBQ is based on four broad behavioral domains (ie, avoidance, modification, substitution, and replacement) associated with fat-related eating patterns. These behavioral domains are composed of specific dietary behaviors (factors). Using a scoring system that allowed all participants to be included in all analyses, we identified a set of factors characterizing eating patterns in our sample that differed from those reported previously. When the factors were converted to scales using unit scoring, the average value suggested a tendency toward a higher fat eating pattern. Results indicate that although behavioral domains appear to be constant across populations, fat-related eating patterns are not. These observations have implications for understanding the diversity of fat-related dietary patterns across groups and for planning appropriate behavior change strategies.

Helium is an inert gas with unique physical properties that allow it to be used for various respiratory emergencies. Because of its low specific gravity and low viscosity, the passage of helium through the respiratory tract is smoother, more laminar, and less turbulent than either air or oxygen. These properties have prompted the use of helium and oxygen in patients with airway obstructions due to tumor, foreign body, edema, or bronchoconstriction. Helium-oxygen has been used to facilitate bronchoscopy through small diameter endotracheal tubes and to increase the effectiveness of high-frequency jet ventilation. Helium has been successful in the treatment of spinal cord decompression sickness seen in divers. Helium-oxygen mixtures are commercially available and may be useful in the emergency department to treat patients with airway obstruction. This article reviews literature concerning the use of helium-oxygen gas mixtures in the emergency department. Additional research conducted in the future may further define the use of this unique gas mixture in the emergency department.

Comorbidity, the co-existence of multiple chronic conditions in a single individual, has been shown to modify the prognosis of disease states. To estimate disease burdens within and among racial subpopulations of the United States, we examined cross-sectional patterns of comorbidity and their impact on survival using data from the NHANES-1 Epidemiologic Follow-up Study (NHEFS). We considered the occurrence of four cardiovascular conditions: stroke, coronary heart disease, hypertension and diabetes. We summarize the joint occurrence of these four conditions using these different methodologies: the number of conditions occurring in each individual and two summaries that weight the conditions according to their prognostic significance. Using all three methodologies, we found an excess burden of chronic disease in black women as compared with white women. Black men had an excess burden compared to white men for the first two methodologies. However, when we model the relationship of the joint occurrence of the conditions to subsequent mortality, black men and white men are seen to have a similar burden. This similarity of black and white men is due to an interaction between race and prevalent stroke in men that we hypothesize may be due to the small number of black men available for study. Given the apparent conditioning effect of co-existing diseases, it is evident that estimation of disease burdens among groups that differ in terms of health status, in particular among U.S. blacks and whites, requires accounting for the occurrence of multiple chronic diseases. Using either the number of conditions or the prognosis weighted summary, we demonstrated a higher burden of the conditions considered in blacks that in whites in a sample of the U.S. population.

In the context of a collaborative study on the epidemiology of hypertension in populations of West African origin procedures for standardization of the measurement of blood pressure were evaluated. Comparisons of mean levels of blood pressure, which in large part determine prevalence rates, are highly sensitive to differences in technique. While rotating a single field team may be the ideal approach to multisite studies, it is not practical in international collaborative research. Appropriate techniques to standardize multiple teams over a long period of time have not been well developed, however. In the present study 8981 individuals were examined in eight sites in six countries with the standard mercury sphygmomanometer. An evaluation of the effectiveness of central training, site visits, monitoring of digit preference, and the use of an electronic device for internal standardization is described. In all but one of the sites reliability was high and comparable to the observers at the Coordinating Center. Digit preference for the entire set of measurements was limited (frequency of terminal zero = 23.5% for systolic and 28.9% for diastolic readings) and could be shown to have virtually no effect on prevalence rates or correlation estimates. Mean differences among observers within a given site and between sites were small (+/- 0-5 mmHg). While logistically complex, these methods can provide the basis for standardization in international comparative blood pressure surveys.

Interleukin-1 (IL-1) can induce intestinal epithelial cells (IEC) to produce several cytokines and acute phase proteins, suggesting that IEC may be important in a cytokine network at the intestinal mucosa to amplify the effects of IL-1 during an inflammatory response. However, little is known about the type of IL-1 receptor expressed by IEC and the effect of cytokines on the expression of these receptors. In this study, the expression by IEC of IL-1 receptor Type I (IL-1RI) and type II (IL-1RII) mRNA was examined by reverse transcriptase polymerase chain reaction. Both isolated rat IEC and the rat IEC-6 intestinal epithelial cell line were found to express mRNA for IL-1RI but not IL-1RII. Stimulation of the IEC-6 cells with IL-1beta or TNF-alpha down-regulated the expression of mRNA for IL-1RI at 24 hr, yet transforming growth factor-beta1 was found to have no effect. These results suggest a possible mechanism to limit the effect of IL-1 on IEC function during the mucosal inflammatory response by down-regulating the expression of the Type I IL-1 receptor.

When a major urban hospital received notice it would no longer have resident physicians to serve its perinatal population, nurses and physicians joined forces with a private university to develop a curriculum for advanced level caregivers. This willingness to rise to a challenge helped to create the Perinatal Nurse Practitioner Program and has paved the way for other needed inpatient nurse practitioner roles.

A 22-year-old female presented to the Emergency Department after the acute onset of left hemiparesis. Marked prolongation of the partial thromboplastin time, mild thrombocytopenia, a history of syphilis, and recent spontaneous abortion suggested the diagnosis of antiphospholipid antibody syndrome, an unusual cause of ischemic stroke. This case illustrates the clinical and laboratory features of this uncommon disorder.

Adenosine (ADO) is an endogenous cardioprotective autacoid that exerts receptor-mediated cardioprotection from ischemic-reperfusion injury. This study tested the hypothesis that blood cardioplegia (BCP) supplemented with ADO reduces postischemic left ventricular dysfunction in ischemically injured hearts. Twenty-one anesthetized dogs on total bypass were subjected to 30 minutes of normothermic global ischemia. Cold (4 degrees C) potassium BCP was then delivered every 20 minutes for 60 minutes of cardioplegic arrest. In 7 dogs, unsupplemented BCP was used; in 7 dogs, BCP was supplemented with 400 mumol/L ADO; and, in 7 dogs, ADO receptors were blocked with 8-p-sulfophenyltheophylline (30 mg/kg) given with 400 mumol/L ADO in BCP. Preischemic and postischemic left ventricular systolic function was assessed by the slope and volume axis intercept of the end-systolic pressure-volume (impedance catheter) relationship (ESPVR). In unsupplemented BCP, the postischemic slope of the ESPVR was significantly depressed by 42% versus the preischemic value (from 6.8 +/- 1.2 mm Hg/mL to 3.9 +/- 0.4 mm Hg/mL; p < 0.05 versus the preischemic value). In contrast, BCP supplemented with ADO was found to restore the postischemic ESPVR slope to preischemic levels (7.7 +/- 1.0 mm Hg/mL versus 7.4 +/- 1.2 mm Hg/mL, respectively). This cardioprotection was reversed by 8-p-sulfophenyltheophylline (9.9 +/- 1.5 mm Hg/mL versus 4.5 +/- 0.7 mm Hg/mL; p < 0.05 versus the preischemic value). Postischemic plasma creatinine kinase activity was elevated equally in all groups over the baseline values. We conclude that ADO in BCP attenuates postcardioplegia dysfunction in severely injured hearts through the operation of receptor-mediated mechanisms.

This study tests the hypothesis that the adenosine deaminase inhibitor pentostatin (2-deoxycoformycin), when given before ischemia or during infusions of blood cardioplegia, augments interstitial adenosine levels and prevents postcardioplegia dysfunction in hearts with antecedent ischemia. Twenty-one anesthetized dogs were placed on cardiopulmonary bypass, and the hearts were made globally ischemic for 30 minutes. Dogs received blood cardioplegia with no pentostatin (BCP group, n = 6), pretreatment pentostatin (0.2 mg/kg) infused 5 minutes before global ischemia (PS-PTx group, n = 7), or pentostatin included only in the blood cardioplegia without pretreatment (PS-BCP group, n = 8). Microdialysate myocardial adenosine levels (an index of interstitial fluid levels) increased only modestly in the BCP group (from 0.55 +/- 0.13 microM to 2.64 +/- 0.50 microM) and the PS-BCP group (from 0.55 +/- 0.18 microM to 1.08 +/- 0.48 microM) during normothermic ischemia, but interstitial adenosine levels were not augmented further during cardioplegic arrest in either group. In contrast, the adenosine level in the PS-PTx group was significantly (p < 0.05) augmented during global ischemia (from 0.50 +/- 0.13 microM to 63.16 +/- 28.08 microM) and cardioplegia infusion (to 15.26 microM +/- 5.61 microM). Relative to baseline, postischemic left ventricular performance (end-systolic pressure-volume relation) was depressed in both the BCP (from 5.5 +/- 1.2 mm Hg/mL to 3.8 +/- 0.4 mm Hg/mL) and PS-BCP groups (from 7.1 +/- 0.9 mm Hg/mL to 3.8 +/- 0.7 mm Hg/mL). In contrast, PS-PTx restored postischemic performance (from 6.2 +/- 0.5 mm Hg/mL to 7.5 +/- 0.9 mm Hg/mL).(ABSTRACT TRUNCATED AT 250 WORDS)

This study tests the hypothesis that blood cardioplegia (BCP) attenuates endothelial dysfunction related to nitric oxide after global normothermic ischemia, cardioplegic arrest, and reperfusion in anesthetized open-chest dogs placed on cardiopulmonary bypass. The dogs were divided into five groups to identify the time when endothelial injury occurred: group 1 = control without ischemia; group 2 = 45 minutes of normothermic ischemia only; group 3 = 45 minutes of normothermic ischemia plus unmodified reperfusion; group 4 = 45 minutes of ischemia plus intermittent BCP without reperfusion; and group 5 = ischemia plus BCP and reperfusion. In vitro coronary vascular relaxation responses to the nitric oxide stimulator acetylcholine (endothelium-dependent, receptor-dependent), the calcium ionophore A23187 (endothelium-dependent, receptor-independent), and acidified NaNO2 (endothelium-independent) were measured at the end of the protocol. Maximum in vitro coronary vascular responses to acetylcholine were similar among groups 1, 2, and 4, indicating an absence of endothelial injury. In contrast, significantly impaired relaxations to acetylcholine were demonstrated in the two reperfused groups (groups 3 and 5). Relaxation responses to A23187 and NaNO2 were not altered markedly in any group. Electron microscopy showed intact endothelium in groups 1, 2, and 4. However, moderately severe endothelium damage was seen in groups 3 and 5. We conclude that morphologic and functional endothelial damage occurs after blood reperfusion with or without BCP, and 1-hour hypothermic BCP arrest after normothermic ischemia is not associated with extension of endothelial damage.

The baseline, intra-, and interindividual variability as well as storage stability of carotenoids, tocopherols, and retinoids in human buccal mucosal cells were determined because this information is lacking. All the buccal mucosal cell samples were collected after an overnight fast. In the variability study, 154 subjects (median age 57.5 y) provided three samples each at 7-10-d intervals over a 1-mo period. In the stability study, 13 young volunteers provided four samples each before and during the 11 d of oral administration of beta-carotene, alpha-tocopherol, and vegetable juice; the cells were pooled and stored as a pellet at -80 degrees C. Eleven micronutrients were analyzed simultaneously with HPLC. The results indicated that 1) lycopene and beta-carotene were the two major carotenoids, retinol was not detected in most cell samples; 2) the intra-individual variability was small, but the interindividual variability was very large; 3) two measurements of micronutrient concentration in fasting buccal mucosal cells should be adequate to establish a representative baseline for each micronutrient; and 4) the micronutrients under the storage conditions were stable for > or = 8 mo.

The role of oxygen (O2) in blood cardioplegia (BCP) remains controversial. On the one hand, O2 reduces ischemic injury between BCP infusions by maintaining energy production through oxidative pathways. On the other hand, O2 carried by blood may not be released to the tissue at 4 degrees C or potentially provides substrate for deleterious O2 radical species. This study tests the hypothesis that O2 is a critical component in myocardial protection afforded by BCP. In 17 anesthetized dogs, left ventricular performance was measured by left ventricular end-systolic pressure-volume relations using the position of the end-systolic pressure-volume relation quantitated by the left ventricular midrange volume intercept at 100 mm Hg (V100) to describe performance. After 30 minutes of global normothermic ischemia, hearts were protected with multidose 4 degrees C BCP for 1 hour of arrest. Oxygen content in BCP was adjusted to 1.1 +/- 0.2 vol% (n = 7; desaturated BCP group), 4.3 +/- 0.5 vol% (n = 5; intermediate oxygenated BCP group), or 10.2 +/- 0.6 vol% (n = 5; saturated BCP group) using a membrane oxygenator interposed in the BCP circuit and aerated with an appropriate mixture of O2, nitrogen, and carbon dioxide. After 1 hour of 37 degrees C reperfusion, 3 of the 7 dogs in the desaturated BCP group failed to generate sufficient cardiac output to discontinue bypass. In the remaining 4 dogs, severe left ventricular depression caused a rightward shift in V100 from 17 +/- 4 to 47 +/- 9 mL (p = 0.02). With intermediate BCP, all hearts were weaned from bypass with marginal left ventricular depression (V100, 20 +/- 5 versus 46 +/- 16 mL; p = 0.10). In contrast, hearts protected with saturated BCP showed no significant increase in V100 (13 +/- 4 versus 24 +/- 13 mL; p = 0.23). We conclude that O2 in BCP is critical to its myocardial protective properties.

The positive inotropism expected with correction of postischemic hypocalcemia might be counterbalanced by potential aggravation of reperfusion injury, in particular by calcium overload. We evaluated the effect of normalizing blood calcium concentration ([Ca2+]) on postischemic left ventricular systolic and diastolic mechanics using oxygen consumption and indices derived from pressure-diameter relations. In 10 open-chest dogs on cardiopulmonary bypass, the hearts underwent 30 minutes of normothermic global ischemia followed by one hour of multidose hypothermic (4 degrees C), hypocalcemic (0.3 mmol/L) blood cardioplegia. After reperfusion, systemic [Ca2+] had decreased to 70% of control (p = 0.017). The left ventricular inotropic state was significantly depressed from baseline (control) values, but was restored to baseline levels by resumption of normocalcemia after one hour of reperfusion. Chamber stiffness increased by 308% (p = 0.006) after hypocalcemic reperfusion but decreased significantly after [Ca2+] correction. Recovery of left ventricular performance with [Ca2+] correction did not augment myocardial oxygen consumption from the postischemic uncorrected state (5.0 +/- 0.3 mL O2/min/100 g versus 5.3 +/- 0.3 mL O2/min/100 g). We conclude that normalizing [Ca2+] after blood cardioplegia improves postischemic left ventricular performance without adversely affecting compliance or oxygen consumption.

The murine lacrimal gland demonstrates a high proportion of both IgA-producing cells and IgA-bearing cells, an observation consistent with tissues of the secretory immune system. This selective accumulation of IgA cells in the lacrimal gland was studied by observing the accumulation of various populations of fluorescein isothiocyanate-labeled lymphocytes in the gland. Labeled spleen cells were found to accumulate equally as well as mesenteric lymph node cells. T cells and T-cell-depleted populations of lymphocytes from spleen also showed migration into the gland. Surface staining of labeled cells found in the gland after 24 hr revealed that IgA-, IgG-, and IgM-bearing cells were all present in high proportions. These experiments demonstrate a random migration of lymphocytes into the lacrimal gland and suggest that the accumulation of IgA-bearing cells in the gland is regulated by the nonvascular microenvironment within the gland.

The association of frequency of alcohol consumption with the seven-year incidence of coronary heart-disease and with mortality both from all causes and from specific causes was examined in a cohort of 11 121 Yugoslav males aged 35-62 at the time of their initial examination. Consumption of alcohol seemed to be inversely related to incidence of coronary heart-disease morbidity and mortality, but not to risk of dying. Those consuming alcoholic beverages most frequently were at increased risk of death from stroke and accidents or violence. The frequency of alcohol consumption was associated with high blood-pressure and serum cholesterol levels. The associations with coronary heart disease and death from all causes could not be fully explained by these covariates.

Within-person variability of nutrient intake is examined using data on 7 consecutive days for 329 men. The variability of nutrient intake within persons differs for the nutrients examined. Some nutrients, such as starch, have small within-person components of variance and are therefore highly reliable even using a single 24-h recall. Others, such a polyunsaturated fatty acids, have large within-person components of variance and are thus less reliable. Within-person variability affects the power of a study to detect differences in nutrient intake between groups and also affects the magnitude of calculated correlation coefficients. For the least reliable nutrient it is estimated that the correlation would be attenuated to two-thirds its true size. Eating patterns in the cohort appear to be nonrandom. Using this nonrandomness of nutrient intake it may be possible to reduce the within-person component of variance using less recalls than is suggested if random eating patterns are assumed.

The synthesis and in vivo biological activity of a series of mono-O-, di-O-, and N2-acyl derivatives of 9-[(1,3-dihydro-2-propoxy)-methyl]guanine (DHPG) are described.