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Biomedical subjects

D E Smith

Publications and source records attributed to D E Smith.

At least 109 records · Page 6Linked to original sources

Vitamin E supplementation decreases lung virus titers in mice infected with influenza.

Effects of vitamin E (E) supplementation on influenza infection were examined in young and old C57BL/6NIA mice fed 30 or 500 ppm of E for 6 weeks and subsequently infected with influenza A/Port Chalmers/1/73 (H3N2). Old mice fed 30 ppm of E had significantly higher lung virus titers on days 2 and 7 after infection than young mice fed 30 ppm of E. Titers on all 3 days were significantly lower in old mice fed 500 ppm of E than in those fed 30 ppm. Significant effects of E on lung virus titers in young mice were observed on only day 5, but E caused more reduction of virus titers in old than in young mice (25-fold vs. 15-fold). An age-associated decline in NK cell activity was restored by 500 ppm of E in old but not young mice. Pulmonary cytotoxic T lymphocyte activity on day 7 was not affected by age or E. These experiments demonstrate that high doses of E significantly enhance influenza viral clearance in aged mice but only modestly affect young mice.

Animals↗

Effects of phospholipase A2, 12-lipoxygenase, and cyclooxygenase inhibitors in the feline pulmonary bed.

The effects of phosphonofluoridic acid, methyl-5,8,11,14-eicosatetraenyl ester (MAFP), a phospholipase A2 inhibitor, on pressor responses to angiotensin II (ANG II), norepinephrine (NE), serotonin (5-HT), the calcium channel opener BAY K 8644, and the thromboxane A2 mimic U-46619 were studied in the pulmonary vascular bed of the intact-chest cat. Under conditions of constant lobar blood flow, injections of ANG II, NE, 5-HT, U-46619, and BAY K 8644 into the lobar arterial perfusion circuit caused dose-related increases in lobar arterial pressure that were reproducible with respect to time. Infusion of MAFP into the perfused lobar artery at doses of 100 to 300 microg/kg for 10 min significantly reduced vasoconstrictor responses to ANG II; however, the phospholipase A2 inhibitor did not alter vasoconstrictor responses to BAY K 8644, 5-HT, NE, or U-46619. The combination of the higher dose of the phospholipase A2 inhibitor MAFP with the phospholipase C inhibitor U-73122 significantly affected vasoconstrictor responses to ANG II, NE, and 5-HT but not to BAY K 8644. In a separate series of animals, the effects of a lipoxygenase inhibitor, baicalein, were investigated. Infusion of baicalein into the perfused lobar artery at doses of 100 microg/kg for 10 min significantly reduced vasoconstrictor responses to ANG II but not the vasoconstrictor responses to BAY K 8644, 5-HT, NE, or U-46619. In a final series of experiments, the effects of a cyclooxygenase inhibitor, meclofenamate, were investigated, and intravenous injection of the meclofenamate at a dose of 2.5 mg/kg did not significantly affect vasoconstrictor responses to ANG II, 5-HT, BAY K 8644, NE, or U-46619. These data provide support for the hypothesis that pulmonary vasopressor responses to ANG II are mediated, in part, by the activation of phospholipase A2, phospholipase C, and the lipoxygenase pathway in the pulmonary vascular bed of the cat.

Animals↗

Seven-year trends in body weight and associations with lifestyle and behavioral characteristics in black and white young adults: the CARDIA study.

OBJECTIVES: This study estimated the amount of weight change in a biracial cohort of young adults and the separate components attributable to time-related and aging-related changes, as well as identified possible determinants of weight change. METHODS: In this population-based prospective study of 18- to 30-year-old African-American and White men and women, body weight and prevalence of overweight were measured from 1985/86 to 1992/93. RESULTS: Average weight increased over the 7 years, increases ranging from 5.2 kg (SE = 0.2, n = 811) in White women to 8.5 kg (SE = 0.3, n = 882) in African-American women. Significant time-related increases in weight, ranging from 2.0 kg (SE = 1.0) in White women to 4.8 kg (SE = 1.0, n = 711) in African-American men, accounted for 40% to 60% of the average total weight gain. Aging-related increases were also significant, ranging from 2.6 kg (SE = 0.8, n = 944) in White men to 5.0 kg (SE = 1.1) in African-American women. The prevalence of overweight increased progressively in each group. Decreased physical fitness was most strongly associated with weight gain in both sexes. CONCLUSIONS: The observed dramatic time-related weight gains, most likely due to secular (period-related) trends, are a serious public health concern.

Adolescent↗

Motivational interviewing to improve adherence to a behavioral weight-control program for older obese women with NIDDM. A pilot study.

OBJECTIVE: The aim of this randomized pilot study was to examine whether the addition of motivational interviewing strategies to a behavioral obesity intervention enhances adherence and glucose control in older obese women with NIDDM. RESEARCH DESIGN AND METHODS: Twenty-two older obese women (41% black) with NIDDM were randomly assigned to 1) a standard 16-week group behavioral weight-control program that provided instruction in diet, exercise, and behavioral modification or 2) the same group behavioral program with three individualized motivational interviewing sessions added. RESULTS: The motivational group attended significantly more group meetings (13.3 vs. 8.9), completed significantly more food diaries (15.2 vs. 10.1), and recorded blood glucose significantly more often (46.0 vs. 32.2 days) than the standard group. Further, participants in the motivational group had significantly better glucose control post-treatment (9.8 vs. 10.8%). Although both groups demonstrated significant weight loss, no differences were apparent between groups. CONCLUSIONS: These results suggest that augmenting a standard behavioral treatment program for obese women with NIDDM with a motivational interviewing component may significantly enhance adherence to program recommendations and glycemic control. Preliminary data warrant further investigation with larger samples and a longer follow-up.

Behavior Therapy↗

Gamma-hydroxybutyrate: an emerging drug of abuse that causes physical dependence.

Gamma-hydroxybutyrate (GHB) is a compound found in mammalian brain which meets many criteria of a neurotransmitter. GHB has been investigated as a tool for inducing absence (petit mal) seizures, for use as an anesthetic, and for treatment of narcolepsy, alcohol dependence and opiate dependence. Since 1990 GHB has been abused in the United States for euphoric, sedative and anabolic effects. Coma and seizures have been reported following abuse of GHB, but dependence liability has received little attention. The neuropharmacology, potential therapeutic uses and acute adverse effects of GHB are reviewed, followed by a case series of eight people using GHB. Adverse effects of GHB may include prolonged abuse, seizure activity and a withdrawal syndrome. This withdrawal syndrome includes insomnia, anxiety and tremor; withdrawal symptoms resolve in 3-12 days. GHB has the potential to cause a significant incidence of abuse and adverse effects. Prolonged use of high doses may lead to a withdrawal syndrome, which resolves without sequelae. Educational efforts should address the narrow therapeutic index, possible physical dependence and dangers of combining GHB with other drugs of abuse.

Adult↗

Beta-oxidation in rabbit liver in vitro and in the perfused ferret liver contributes to retinoic acid biosynthesis from beta-apocarotenoic acids.

The biosynthesis of retinoic acid from beta-apocarotenoic acids was examined for a beta-oxidation-like process using both rabbit liver mitochondrial fractions with various beta-apocarotenoic acids (beta-apo-14'-, beta-apo-12'-, and beta-apo-8'-carotenoic acid) and perfusion in ferret liver through the portal vein with beta-apo-8'-carotenoic acid. The in vitro incubation of beta-apo-8', beta-apo-12'-, and beta-apo-14'-carotenoic acids gave rise to shorter chain beta-apocarotenoic acids as well as retinoic acid. The rate of retinoic acid synthesis from 10 microM beta-apo-8', beta-apo-12'-, and beta-apo-14'-carotenoic acids was 11 +/- 2, 18 +/- 3, and 30 +/- 7 pmol/h/mg of protein, respectively. The stepwise oxidation of beta-apocarotenoic acid in mitochondria was dose-related to both protein concentration and substrate concentration. beta-Apocarotenoic acid oxidation was inhibited in a dose-dependent manner when it was co-incubated with oleoyl-CoA. The in vivo perfusion of ferret liver with beta-apo-8'-carotenoic acid resulted in a linear increase in the retinoic acid concentration of bile, which was completely abolished by co-perfusion of 3-mercaptopropionic acid, an inhibitor of long chain acyl-CoA dehydrogenase, and partially inhibited by 2-tetradecylglycidic acid, an inhibitor of carnitine-palmitoyl-CoA transferase I. However, the formation of retinoic acid from the beta-apocarotenoic acids was not inhibited, either in vitro or in vivo, by citral, an inhibitor of retinal oxidase. Thus, the formation of retinoic acid was not occurring by the central cleavage pathway. These data suggest that the oxidation of intermediate compounds between beta-carotene and retinoic acid may undergo a type of beta-oxidative process to form retinoic acid, which is reminiscent of mitochondrial fatty acid beta-oxidation. This pathway may play an important role in the biosynthesis of retinoic acid from beta-carotene.

Animals↗

Regional pharmacokinetics of 5-bromo-2'-deoxyuridine and 5-fluorouracil in dogs: hepatic arterial versus portal venous infusions.

The purpose of this study was to determine the effect of route of hepatic administration of drug on the regional pharmacokinetics and systemic exposure of 5-fluorouracil (FUra) and 5-bromo-2-deoxyuridine (BrdUrd). A total of 13 mixed-breed male and female dogs were used in these acute studies. Each dog was administered hepatic arterial and portal venous infusions of a single drug, in a cross-over fashion, at two dose rates for a total of four sequential infusions. BrdUrd was studied at 0.250 and 0.500 micromol/min/kg, and FUra was studied at 0.125 and 0.500 micromol/min/ kg. Each infusion lasted 2 h, at which time steady-state plasma concentrations were obtained (ie., gastroduodenal artery, portal vein, hepatic vein, and femoral artery), perfusion rates in hepatic artery and portal vein were measured, and hepatic extraction (as opposed to extraction across the splanchnic region) was directly assessed. BrdUrd and FUra were found to be highly extracted across the liver (E(H) > or = 0.65) at the regional dose rates studied, resulting in low values for the fraction of drug escaping presystemic hepatic elimination (F(H) < or = 0.35). In addition, the regional kinetics (ie., hepatic extraction, fraction escaping first-pass elimination in the liver, and hepatic clearance) and systemic exposure (i.e., CFA) of FUra and BrdUrd were not significantly different following hepatic arterial versus portal venous infusions of drug. Thus, it appears that regional chemotherapy may be applied to halogenated pyrimidines following hepatic arterial, portal venous, and alternating regional dosing routes with no additional risk of systemic toxicity.

Animals↗

Increase in fasting insulin and glucose over seven years with increasing weight and inactivity of young adults. The CARDIA Study. Coronary Artery Risk Development in Young Adults.

To characterize 7-year changes in fasting serum insulin and glucose concentrations, the authors analyzed population-based data on 3,095 nondiabetic black and white men and women who were initially aged 18-30 years in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Measurements were made of fasting insulin (by an assay with little cross-reactivity to proinsulin) and fasting glucose on frozen samples from baseline and Year 7 examinations. Over the 7-year period, mean fasting insulin increased 10-25%, mean fasting glucose increased 7-10%, and mean body mass increased 7-12% across the four race-, sex-groups. The strongest predictor of both insulin increase and glucose increase was an increase in body mass over the 7 years. Adjusted for age and examination time period in race-, sex-specific repeated measures analyses, fasting insulin increased longitudinally by approximately 5 microU/mL per 5 kg/m2 increase in body mass index (p < 0.05). Adjusted for age and time period, fasting insulin increased over the 7 years by approximately 2.5 microU/mL per 0.08 unit increase in waist/hip ratio (p < 0.05), although this association was much stronger cross-sectionally. In a similar model, each 100 unit decrease in physical activity longitudinally predicted a 0.1-0.2 microU/mL increase in fasting insulin (p < 0.05 in black men only); this association was stronger and statistically significant in all race-, sex-groups cross-sectionally. Fasting insulin was not associated with energy intake either cross-sectionally or longitudinally, but age- and time-adjusted associations of insulin change with change in several nutrients (e.g., energy from fat) were statistically significant in whites. The authors conclude that marked increased in weight in young adulthood adversely alters glucose and insulin metabolism, and that, if not reversed, this may lead to harmful health consequences in later life.

Adolescent↗

Subclavian vein anatomic subtypes defined by digital cinefluroscopic venography prior to permanent pacemaker lead insertion.

Digital cinefluoroscopic venography of the subclavian vein was performed in 26 consecutive patients. The optimal stored image of the anticipated venipuncture site was magnified, road mapped, and used to compare with fluoroscopic-guided venipuncture. Two anatomic subtypes for both subclavian veins were observed. For the left subclavian vein, a gradual curve was seen most often (57%), while the remainder (43%) exhibited an "s"-shaped curve. For the right subclavian, a gradual curve was observed most frequently (60%) while an acute 90 degrees angle was noted in the remainder (40%). The "s"-shaped curve in the left subclavian vein necessitated redirection of the needle site both laterally and cranially. In three or 12% of patients venography showed either subclavian thrombosis or a persistent left superior vena cava and lead insertion was moved to the opposite side. Successful venipuncture and subsequent cannulation of the subclavian vein was achieved with the first or second passage of the needle in 22 or 85% of the 26 patients. Digital cinefluoroscopic venography appears to be both safe and rapid and may facilitate insertion of permanent pacemaker leads into the subclavian vein.

Catheterization, Central Venous↗

Tubular transport mechanisms of quinapril and quinaprilat in the isolated perfused rat kidney: effect of organic anions and cations.

The clearance mechanisms of quinapril and quinaprilat were probed using an isolated perfused rat kidney model. Sixty-four experiments were performed with drug in the absence and presence of classic inhibitors of the organic acid (i.e., probenecid and p-aminohippurate) and organic base (i.e., tetraethylammonium and quinine) transport systems of the proximal tubule. Initial perfusate concentrations of quinapril and quinaprilat were approximately 2.36 microM (or 1000 ng/ml), and transport inhibitors were coperfused at 100-10,000 times the drugs' initial microM concentrations. Quinapril and quinaprilat concentrations were determined in perfusate, urine, and perfusate ultrafiltrate using a reversed-phase HPLC procedure with radiochemical detection, coupled to liquid scintillation spectrometry. Perfusate protein binding was determined using an ultrafiltration method at 37 degrees C. Overall, the clearance ratios of quinapril (total renal clearance divided by fu x GFR) and quinaprilat (urinary clearance divided by fu. GFR) were significantly reduced, and in a dose-dependent manner, by the coperfusion of organic acids but not organic bases. The data demonstrate that the organic anionic secretory system is the primary mechanism by which quinapril and quinaprilat are transported into and across renal proximal cells.

Angiotensin-Converting Enzyme Inhibitors↗

Discordant Duane's retraction syndrome in monozygotic twins.

PURPOSE: To evaluate whether differences in the intrauterine environment caused discordant Duane's retraction syndrome in monozygotic twins. METHODS: Pathology records were reviewed to determine monozygosity. RESULTS: Discordant Duane's retraction syndrome was present in twin boys with identical genetic foundations who had different intrauterine environments. The placenta indicated areas of anastomosis between the two umbilical cords suggestive of twin-to-twin transfusion that resulted in a visible growth discordance. CONCLUSIONS: Intrauterine environment influences ocular development, and twin-to-twin transfusion may cause Duane's retraction syndrome.

Diseases in Twins↗

Recruitment experience in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study.

Several approaches for recruitment of African American adults with renal insufficiency due to hypertension (glomerular filtration rate between 25 and 70 ml/min/1.73 m2) were explored in the Pilot Study for the African American Study of Kidney Disease and Hypertension (AASK). Over a period of 42 weeks, prescreening information was obtained on 2880 individuals, of whom 498 (17%) were evaluated at a screening visit. Two hundred and twenty-five (8%) had an 125I-iothalamate assessment of glomerular filtration rate. Ninety-four of 97 participants who met all the study eligibility criteria were enrolled in the trial. The most common reasons for ineligibility during screening were absence of renal insufficiency or hypertension, presence of diabetes mellitus, and a body mass index above the acceptable level. Overall, an average of 31 prescreen contacts and 8 screening visits were conducted for every randomization (3.3% yield from prescreening to randomization). Screening in clinical practice was the most efficient method for recruitment (12.6% yield from prescreen contact to randomization compared to 1.1% from mass mailing campaigns, 1.3% from mass media campaigns, and 1.7% from referrals by patients with end-stage renal disease). Randomization yields increased with progressively higher age ranges (2.4%, 3.3%, and 6.0% prescreen to randomization yields for those aged < or = 50, 51-60, and 61-70, respectively). A slight majority (51%) of the prescreen contacts were women, but 75% of the randomized participants were men. Our results suggest that clinic-based screening is an effective approach for recruitment of African Americans with hypertension and renal insufficiency into clinical trials. They also suggest that enrollment of African American women in such studies is a special challenge.

Adult↗

Appointment attendance, pill counts, and achievement of goal blood pressure in the African American Study of Kidney Disease and Hypertension Pilot Study.

The African American Study of Kidney Disease and Hypertension (AASK) Pilot Study evaluated the feasibility of conducting a 7-year clinical trial to assess the effect of two levels of blood pressure control based on mean arterial pressure (MAP) (low goal < or = 92 mm Hg or usual goal of 102-107 mm Hg) and three antihypertensive drug regimens (atenolol, amlodipine, or enalapril) as initial therapy in slowing the decline of renal function in African Americans with clinically diagnosed hypertensive nephrosclerosis. Ninety-four African American men and women between 18 and 70 years of age were randomized and followed for an average of 4.6 months. On average participants attended 87.5% of the scheduled monthly follow-up visits and achieved an acceptable level of medication adherence (80%-100% of prescribed doses by pill count) at 65.4% of those visits Blood pressure levels within goal were observed in 17.5% and 25.6% of the participants in the low- and usual MAP goal groups, respectively. Neither attendance nor medication adherence by pill count was associated with attainment of goal blood pressure. Although AASK Pilot Study participants maintained excellent attendance, their pill counts were lower than previously reported among clinical trial participants and goal blood pressure levels were difficult to achieve during the short period of follow-up.

Adult↗

Effect of blood pressure control and antihypertensive drug regimen on quality of life: the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study.

The African American Study of Kidney Disease and Hypertension (AASK) Pilot Study evaluated the feasibility of carrying out a randomized, multicenter, 7-year clinical trial to determine the effects of two goal levels of blood pressure control and three antihypertensive drug regimens on decline in glomerular filtration rate in African Americans with clinically diagnosed hypertensive nephrosclerosis. Participants were randomized to either a usual mean arterial blood pressure (MAP) goal group (102-107 mm Hg) or a low-MAP goal group (< or = 92 mm Hg) and to a drug regimen (initial therapy with either atenolol, amlodipine, or enalapril). Quality of life was assessed by the Medical Outcomes Short-Form 36 (MOS SF-36) at baseline and the last follow-up visit for 84 of the 94 participants of the AASK Pilot Study. Symptoms were assessed at baseline and throughout the course of therapy by participant self-report. Mean SF-36 scores increased significantly on physical functioning (9.2), role limitations (physical) (19.0), social functioning (9.0), and vitality dimensions (5.6) from baseline to the last follow-up visit in the usual MAP goal group. Scores for the eight health dimensions assessed by the MOS SF-36 did not change significantly during the same time period either in the low-MAP goal group or in any of the drug regimens. The mean score for general health perception was significantly lower at the last follow-up visit in the enalapril drug regimen (49.9) compared to drug regimens with atenolol (65.4) or amlodipine (63.9). Physical functioning, role limitations (emotional), social functioning, mental health, vitality, and general health perception scores were negatively correlated with self-reported symptoms during treatment. We conclude that selected dimensions of quality of life improved during the AASK Pilot Study only in participants randomized to the usual MAP goal group. Significant differences between MAP goal groups and drug regimens at the end of follow-up were observed for only a few health dimensions.

Adult↗

Effects of porcine relaxin on induced parturition in beef heifers.

Two-year-old crossbred beef heifers were used to test the effects of porcine relaxin (pRelaxin) alone, or in combination with dexamethasone, on the induction of parturition, the incidence of dystocia, and retained placentas. Effects of treatment on pelvic area, postpartum interval, milk production, colostrum quality, calf birth weight, calf vigor, and calf performance were also evaluated. On Day 275 of gestation, heifers from two fetal-sire groups were randomly assigned to one of four groups in a 2 x 2 factorial design and received; no treatment (controls, n = 19), 20 mg of dexamethasone intramuscularly (im) (n = 22), 5 mg of pRelaxin (3,000 U/mg) im (n = 19), or 20 mg of dexamethasone plus 5 mg of pRelaxin (n = 17). Length of gestation (in days) was less (P < 0.05) in heifers treated with dexamethasone (279.8 +/- 1.0) than in controls (286.6 +/- 0.9), but was not influenced (P > 0.05) by treatment with pRelaxin. The incidence of retained placentas in heifers treated only with dexamethasone (27.3%) was not reduced by concomitant treatment with pRelaxin (35.3%). Retained placentas were not observed in any control heifers and in only one heifer (5.2%) treated solely with pRelaxin. Ease of calving (1 = unassisted, 5 = abnormal presentation) was not influenced by treatment (P > 0.05), even though birth weights (in kilograms) of calves from heifers treated with dexamethasone (36.4 +/- 0.8) were less (P < .01) than those of calves from nondexa-methasone-treated heifers (39.2 +/- 0.8). Dexamethasone tended to reduce (P < 0.07) calf vigor (1 = healthy and strong, 5 = dead on arrival; 1.48 +/- 0.11 vs. 1.18 +/- 0.11), but was not (P > 0.05) influenced by pRelaxin. The duration of the postpartum anestrous interval (73.1 +/- 1.8 d across groups) and pelvic areas following treatment and parturition were not influenced (P > 0.05) by dexamethasone or pRelaxin. Although determinants of colostrum quality (P < 0.01) and quantity (P < 0.08) of milk produced were influenced by dexamethasone, adjusted 205-d weights of calves did not differ (P > 0.05) among groups. In conclusion, treatment with pRelaxin alone failed to induce parturition or, when combined with dexamethasone, to reduce the incidence of retained placentas.

Animals↗

Dietary folate protects against the development of macroscopic colonic neoplasia in a dose responsive manner in rats.

BACKGROUND AND AIMS: Diminished folate status is associated with enhanced colorectal carcinogenesis. This study investigated the potential chemopreventive role of dietary folate in the dimethylhydrazine colorectal cancer model. SUBJECTS AND METHODS: Sprague-Dawley rats were fed diets containing either 0, 2 (daily dietary requirement), 8 or 40 mg folate/kg diet for 20 weeks. After five weeks of diet, rats were injected with dimethyl-hydrazine (44 mg/kg) weekly for 15 weeks. Fifteen weeks after the first injection of dimethylhydrazine, all rats were killed. Folate status was determined, and the entire colorectum from each rat was analysed for macroscopic and microscopic neoplasms. RESULTS: Plasma and colonic folate concentrations correlated directly with dietary folate levels (p < 0.005). The incidence of microscopic neoplasms was similar among the four groups. However, the incidence and the average number of macroscopic tumours per rat decreased progressively with increasing dietary folate levels up to 8 mg/kg diet (p < 0.05). In the strongly procarcinogenic milieu used in this study, folate supplementation at 20 times the basal requirement was associated with rates of macroscopic tumour development that were intermediate, and not statistically distinct, from rates observed at either 0 or 8 mg/kg diet. CONCLUSIONS: These data indicate that in this rat model, (a) increasing dietary folate up to four times the basal requirement leads to a progressive reduction in the evolution of macroscopic neoplasms from microscopic foci; and (b) folate supplementation beyond four times the requirement does not convey further benefit.

Analysis of Variance↗