Reassessing the relevance of pharmacoeconomic analyses in formulary decisions.
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Chemistry, Pharmaceutical↗
Biomedical subjects
J A Johnson
Publications and source records attributed to J A Johnson.
Influence of season on dietary composition, intake, and digestion by beef steers grazing mixed-grass prairie in the northern Great Plains.
We used six beef steers (377 +/- 12.7 kg) to evaluate the effect of advancing season on dietary composition, forage intake, and digestion. Six 10-d sample collections were conducted from mid-June to mid-December 1995. Diet quality data demonstrated a linear (P < .01) decline in CP and in vitro OM digestibility (IVOMD), whereas NDF, ADF, acid detergent-insoluble CP (ADICP; percentage of CP), and undegradable intake protein (UIP; percentage of CP) increased linearly (P < .01) with advancing season. Fecal output and ruminal OM fill (percentage of BW) demonstrated linear and cubic responses (P < .10) across the grazing season. Intake of OM (percentage of BW) followed quadratic and cubic (P < .10) patterns across season. Rate (percentage per hour) of in situ NDF disappearance (ISNDFD) decreased and lag time increased linearly (P < .01) with advancing season. Likewise, quadratic (P < .07) and cubic (P < .06) responses were observed for rate and lag time of ISNDFD. The rapidly degraded CP fraction increased (P < .10) linearly, and the rate of in situ CP disappearance (ISCPD) followed a linear and quadratic decrease (P < .10) with advancing season. In summary, these data indicate decreases (P < .10) in dietary CP, IVOMD, ISNDFD, and ISCPD with advancing season. In addition, seasonal increases (P < .10) in forage NDF, ADF, ADICP, UIP (percentage of DM) and fecal output were observed and correspond to the grazing of increasingly mature forage. These data suggest that mixed-grass range forage consumed by cattle in western North Dakota during November and December is deficient in degradable intake protein (DIP). Investigation of protein supplementation (particularly DIP) during these times is warranted.
Animal Feed↗
German women in chemistry, 1925-1945 (Part II).
The paper traces the role of German women into the chemistry profession from 1925 to 1945, examining their relative numbers and experience in higher education, in academic and industrial careers as well as in professional organizations such as the Verein Deutscher Chemikerinnen. The paper examines the effect of the 1930s Depression, National Socialism, and World War II on women chemists, considering both general trends as well as the experiences and achievements of several individual women in a variety of situations. Finally, it considers the longterm consequences of these developments, such as the Nazi expulsion of Jewish women, destruction of women's organizations and devaluing of women's achievements, in limiting the recognition and participation of German women chemists after 1945.
Chemistry↗
Simultaneous measurement of myocardial oxygen consumption and blood flow using [1-carbon-11]acetate.
UNLABELLED: [1-Carbon-11]acetate has been used as a tracer for oxidative metabolism with PET. The aim of this study was to validate, in humans, a previously proposed two-compartment model for [1-11C]acetate for the noninvasive measurement of myocardial oxygen consumption (MVO2) and myocardial blood flow (MBF) with PET. METHODS: Twelve healthy volunteers were studied with [13N]ammonia, [1-11C]acetate and PET. Myocardial oxygen consumption was invasively determined by the Fick method from arterial and coronary sinus O2 concentrations and from MBF obtained by [13N]ammonia PET. RESULTS: Directly measured MVO2 ranged from 5.2 to 11.1 ml/100g/min, and MBF ranged from 0.48 to 0.88 ml/g/min. Oxidative flux through the tricarboxylic acid cycle, reflected by the rate constant k2, which correlated linearly with measured MVO2 [k2 = 0.0071 + 0.0074(MVO2); r = 0.74, s.e.e. = 0.015]. With this correlation, MVO2 could be estimated from the model-derived k2 value by MVO2 = 135(k2) - 0.96. The slope of this relationship was close to that previously obtained in rats and implies that the tricarboxylic acid cycle intermediate metabolite pool sizes are comparable. The net extraction (K1) of [1-11C]acetate, measured by PET, from blood into myocardium correlated closely with MBF by K1 = 0.15 + 0.73(MBF) (r = 0.93, s.e.e. = 0.033) and, thus, provided noninvasively obtainable measures of blood flow. CONCLUSION: The proposed compartment model for [1-11C]acetate fits the measured kinetics well and, with proper calibration, allows estimation of absolute MVO2 rather than only an index of oxidative metabolism. Furthermore, [1-11C]acetate-derived estimates of MBF are feasible.
Acetic Acid↗
A research-based guideline for appropriate use of transdermal fentanyl to treat chronic pain.
PURPOSE/OBJECTIVES: To describe a research utilization project intended to develop, implement, and evaluate a research-based guideline for the use of transdermal fentanyl. DATA SOURCES: The guideline was based on existing literature, clinical expert knowledge, manufacturer recommendations, and cost considerations. Principles of guideline development and evaluation were based on recommendations from the Agency for Health Care Policy and Research. DATA SYNTHESIS: A comparison of data from baseline to six months after guideline implementation revealed improvements in all criteria. Most of the improvements were maintained at 18 months postguideline implementation. CONCLUSIONS: The guideline improved the appropriate use of transdermal fentanyl. Ongoing education and monitoring is necessary to maintain change in practice. IMPLICATIONS FOR NURSING PRACTICE: The cost-effective use of expensive technology is a concern in the area of health care. Nurses need to promote the appropriate use of pain-management techniques to provide quality care for patients with chronic pain. Guidelines will help nurses to support the use of higher-cost medications in this subpopulation of patients.
Administration, Cutaneous↗
Cholera in Lima, Peru, correlates with prior isolation of Vibrio cholerae from the environment.
The authors utilized a recently developed DNA probe technique to obtain quantitative data on occurrence of Vibrio cholerae in samples collected monthly from 12 environmental sites in Lima, Peru, from November 1993 through March 1995. Peak V. cholerae counts ranged from 10(2)/ml to 10(5)/ml, with the highest counts in sewage-contaminated areas and irrigation water. With our methodology, no V. cholerae cases were detected at any site during the winter months of July through October. Counts were detectable in the environment before onset of cholera in the community, with counts at "cleaner" sites upriver correlating significantly with occurrence of community disease 2 and 3 months later. In sites with heavy sewage contamination, V. cholerae could still be detected before the onset of cases in the community; however, in contrast to upriver sites, counts at these latter sites correlated most closely with the number of concurrently occurring cholera cases. These data support a model of cholera seasonality in which initial increases in number of V. cholerae in the environment (possibly triggered by temperature) are followed by onset of illness in the community, with these human cases further amplifying the organism as the epidemic cycle proceeds.
Cholera↗
Classification of Vibrio vulnificus strains by the carbohydrate composition of their capsular polysaccharides.
Pathogenic bacteria are often classified on the basis of the complex polysaccharides found on the surface, usually capsular polysaccharides or lipopolysaccharides. It is common in clinical practice to use reactivity with antisera specific to the various cell surface carbohydrates for this purpose. In this work, we describe a chemotyping method for bacterial capsular polysaccharides which is based on a carbohydrate analysis of an acid hydrolysate of the capsule. High-performance anion-exchange chromatography at high pH (HPAE) with electrochemical detection, which is used for analysis of the hydrolysate, shows preferential sensitivity for sugars. A single acid hydrolysis condition is chosen for screening a large collection of bacterial isolates and a computerized autosampler is used to make possible a large number of rapid analyses. This procedure does not yield a quantitative carbohydrate analysis for the sample but produces a fingerprint which can be used to discriminate among isolates which have different capsular polysaccharide structures. The procedure has been applied to a collection of 120 isolates of Vibrio vulnificus, a water-born species common in shellfish which causes septicemia in immunocompromised individuals, most often from eating of raw oysters. The collection of bacterial isolates includes strains from both clinical cases of septicemia and from such environmental sources such as sea water, sediments, and shellfish. Our results show that a number of unusual sugars including many amino sugars are found in these polysaccharides and that a wide variety of capsular carbotypes in V. vulnificus may be readily distinguished by the HPAE fingerprint.
Anion Exchange Resins↗
Omphalocele in Miller-Dieker syndrome: expanding the phenotype.
We report on a patient prenatally diagnosed with omphalocele, mild cerebral ventriculomegaly, nuchal fold thickening, and cystic changes in the umbilical cord who was found postnatally to have lissencephaly type I. Prenatal chromosome analysis showed a normal male karyotype; however, postnatal high resolution banding and FISH analysis, using a probe for locus D17S379 in chromosome region 17p13.3, demonstrated a deletion at 17p13.3 consistent with Miller-Dieker syndrome (MDS). A review documented four more cases with MDS/isolated lissencephaly/17p-, with omphalocele. Because MDS is a contiguous gene disorder, we speculate that a gene or genes in this region have a major role in the closure of the lateral folds or the return of the midgut from the body stalk to the abdomen at 5-11 weeks of gestation. Prenatal diagnosis of omphalocele with mild ventriculomegaly should prompt FISH analysis for a deletion in 17p13.3.
Abnormalities, Multiple↗
Drug-related morbidity and mortality and the economic impact of pharmaceutical care.
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Ambulatory Care↗
Translocation inhibitors define specificity of protein kinase C isoenzymes in pancreatic beta-cells.
The protein kinase C (PKC) family consists of 11 isoenzymes. Following activation, each isoenzyme translocates and binds to a specific receptor for activated C kinase (RACK) (Mochly-Rosen, D. (1995) Science 268, 247-251) that provides an anchoring site in close proximity to the isoenzyme's specific substrate. Pancreatic islet cells contain at least six PKC isoenzymes (Knutson, K. L., and Hoenig, M. (1994) Endocrinology 135, 881-886). Although PKC activation enhances insulin release, the specific function of each isoenzyme is unknown. Here we show that following stimulation with glucose, alphaPKC and epsilonPKC translocate to the cell's periphery, while deltaPKC and zetaPKC translocate to perinuclear sites. betaC2-4, a peptide derived from the RACK1-binding site in the C2 domain of betaPKC, inhibits translocation of alphaPKC and reduces insulin response to glucose. Likewise, epsilonV1-2, an epsilonPKC-derived peptide containing the site for its specific RACK, inhibits translocation of epsilonPKC and reduces insulin response to glucose. Inhibition of islet-glucose metabolism with mannoheptulose blocks translocation of both alphaPKC and epsilonPKC and diminishes insulin response to glucose while calcium-free buffer inhibits translocation of alphaPKC but not epsilonPKC and lowers insulin response by 50%. These findings illustrate the unique ability of specific translocation inhibitors to elucidate the isoenzyme-specific functions of PKC in complex signal transduction pathways.
Animals↗
Investigating the relationship between beta-blocker and antidepressant use through linkage of the administrative databases of Saskatchewan Health.
The main objectives of this research were to confirm previous reports of an increased risk of antidepressant use subsequent to propranolol therapy, and to determine whether this higher relative risk (RR) is indicative of depressive symptoms as a side-effect of the drug's use. 'New' users of beta-blockers, other antihypertensives or diuretics in two separate years were identified from records of Saskatchewan Health. Incidence of concurrent antidepressants prescribing was determined in the year after initiating therapy with a cohort drug. Medical claims were examined to identify physician services and diagnoses associated with cohort drug and antidepressant prescriptions. Risk of concurrent antidepressant use in new propanolol users aged 20-39 years was approximately double that of new diuretic users [RR 2.2 (1.5-3.3) in 1984 and 2.0 (1.1-3.5) in 1990/91]. When cases with a diagnosis of migraine headache were excluded, the risk of concurrent propranolol/antidepressant use was age- and sex-dependent, but not consistent for the two study years. It was concluded that although the risk of concurrent antidepressant use was greater in younger propranolol users, the risk cannot be solely attributed to depressive side-effects of the drug. The purposes of this paper were to present the methods employed in linking the databases of Saskatchewan Health, describe the results of the analysis, and to highlight the methodologic problems that arose.
Journal Article↗
Differences between blacks and whites in plasma protein binding of drugs.
OBJECTIVE: Disopyramide and salicylic acid were used as model compounds to characterize racial differences in binding of drugs by alpha 1-acid glycoprotein (AGP) and albumin, respectively. Drug-free plasma was collected from 29 healthy volunteers (15 white, 14 black). Disopyramide and salicylic acid unbound fractions (fu) in plasma were determined by equilibrium dialysis using 14C-disopyramide and 14C-salicylic acid. RESULTS: Disopyramide unbound fractions were significantly higher in blacks than whites (0.131 vs 0.113) as were salicylic acid unbound fractions (0.053 vs 0.048). When unbound fractions were corrected for AGP and albumin concentration, racial differences were no longer present. CONCLUSION: Many drugs which bind to AGP and/or albumin may exhibit racial differences in unbound fractions. However, these differences are likely explained by differences in protein concentrations rather than differences in the number of binding sites on the protein or racial differences in affinity of the protein for drugs.
Adult↗
Separation and quantitation of linoleic acid oxidation products in mammary gland tissue from mice fed low- and high-fat diets.
We have developed an assay for the isolation and quantitation by gas chromatography-mass spectrometry (GC-MS) of free 9- and 13-hydroxyoctadecadienoic acid (9-HODE, 13-HODE) in the mammary glands of female mice. Internal standards consisting of 18O2-labeled analogs of 9- and 13-HODE are added to pulverized frozen tissue prior to extraction with ethanol. Nonlipid materials are removed in a chloroform/methanol/water step. The remaining lipid material is methylated with ethereal diazomethane, and much of the nonoxygenated fatty acid methyl esters are removed via silica solid-phase extraction. Samples are either further derivatized with bis(trimethylsilyl)trifluoroacetamide to form the trimethylsilyl ethers for quantitative analysis by GC-MS or are analyzed as the methyl esters by chiral high-performance liquid chromatography to determine the enantiomeric distribution of the 9- and 13-HODE. The extraction and quantitation protocol was applied to the analysis of mammary glands for free 9- and 13-HODE from mice fed isocaloric diets containing 20% corn oil, 5% corn oil, or 20% beef tallow. Chiral analysis of the products showed higher production of 13(S)-HODE relative to 13(R)-HODE; the enantiomeric excess is most likely due to enzymatic production of 13-HODE superimposed on a background of autoxidative production of 13(R)- plus 9(S)- and 9(R)-HODE. In addition, the effect of sample handling and storage conditions on the formation of 9- and 13-HODE in the samples was assessed by exposing aliquots of a common pool of rat mammary gland tissue to specified conditions prior to analysis. This methodology will be important during investigations of the contribution of linoleate oxidation products to the enhancement of mammary tumorigenesis by dietary fat.
Analysis of Variance↗
Dehydroepiandrosterone-sulfate inhibits pancreatic carcinoma cell proliferation in vitro and in vivo.
BACKGROUND: Dehydroepiandrosterone-sulfate (DHEA-S) is a potent inhibitor of glucose-6 phosphate dehydrogenase, the rate limiting enzyme of the hexose monophosphate shunt, a biochemical pathway that provides substrate for DNA synthesis in neoplastic tissue. DHEA-S has been shown to inhibit the growth of neoplasms arriving from human skin, lung, colon, and mammary tissue. This study evaluates the effect of DHEA-S on human pancreatic cancer cell lines in vitro and in vivo. METHODS: In vitro, the human pancreatic adenocarcinoma cell lines MiaPaCa-2, Capan-1, Capan-2, CAV and Panc-1 were treated with concentrations of 1.9 mumol/L to 1000 mumol/L DHEA-S in 1% dimethylsulfoxide (DMSO) for 5 consecutive days. Cell proliferation was determined by a nonradioactive cell proliferation assay and compared with DMSO treated controls. In vivo testing was performed by inoculating two cell lines, MiaPaCa-2 and Panc-I, into the flank of 40 male nude athymic mice in four study groups. After 1 week of growth, 667 mg/kg DHEA-S in 1% DMSO or 0.2 ml 1% DMSO alone in the control group was administered by daily intraperitoneal injection. Body weight and tumor size was recorded weekly, and tumor weight was measured after 3 weeks of treatment. RESULTS: In vitro cell proliferation was decreased in the five cell lines by 36% to 62% of controls (p < 0.001) at 500 mumol/L DHEA-S. In vivo, after 2 weeks, tumor size was only 76% (p < 0.008) and 67% (p < 0.005) of the controls. After 3 weeks of treatment, tumor size was 73% (p < 0.001) and 53% (p < 0.001) of controls, and tumor weight was decreased by 73% in MiaPaCa-2 (p < 0.001) and 66% in Panc-1 (p < 0.001). Radioimmunoassay measurements of DHEA-S and testosterone from DHEA-S treated mouse plasma showed a significant increase in circulating levels of these hormones. CONCLUSIONS: DHEA-S achieves high serum levels after intraperitoneal injection without elevation of serum testosterone levels and produces no significant toxicity. Treatment with DHEA-S results in a significant reduction of proliferation of human pancreatic cancer cells in culture and when grown as subcutaneous tumors in athymic nude mice.
Adenocarcinoma↗
Prenatal diagnosis and management of neonatal alloimmune thrombocytopenia.
Neonatal alloimmune thrombocytopenia (NAIT) is an uncommon (1 in 2,000 livebirths) but serious disorder characterized by marked thrombocytopenia in the fetus and neonate. Platelet destruction is caused by a maternal antibody directed against a fetal platelet antigen inherited from the father and lacking in the mother's platelets. Intracranial hemorrhage (ICH) is the most devastating complication of NAIT, affecting approximately 20% of all proven cases, up to 50% of which occur antenatally. Because close to 100% of subsequent pregnancies will be equally or more severely affected, antenatal management directed at preventing ICH in utero has assumed great clinical importance. In recent years, considerable progress has been made in this regard, and although clinical uncertainties still exist, the natural history of this disease and its response to various antenatal interventions have become reasonably well understood. This review will focus on the diagnosis and current management of NAIT, including controversies surrounding current treatment modalities and future prospects for treatment and prevention.
Blood Platelets↗
Cyclic testing of flexor tendon repairs: an in vitro biomechanical study.
Forty cadaveric flexor digitorum profundus tendons were repaired using the Tajima, Halsted, Silfverskiold, or Savage techniques. The tendons were cyclically loaded in sets of 4,000 cycles beginning at 25 N and increasing by 10-N increments until failure occurred. Gap formation was continuously monitored with an extensiometer. Only the Savage repair group consistently withstood 4,000 cycles of 25-N loading, with respect to 2-mm gap formation and repair rupture. Tendon repairs subjected to cyclic loading demonstrated gap formation and repair rupture at lower loads than with static testing. Of the methods of flexor tendon repair tested, only the Savage technique could withstand simulated early active motion.
Biomechanical Phenomena↗
Influence of race or ethnicity on pharmacokinetics of drugs.
Review of the current literature on racial differences in pharmacokinetics of drugs supports the premise that only pharmacokinetic processes which are biologically or biochemically mediated have the potential to exhibit differences between racial or ethnic groups. Thus, the pharmacokinetic factors which can be expected to potentially exhibit racial differences are (1) bioavailability for drugs which undergo gut or hepatic first-pass metabolism, (2) protein binding, (3) volume of distribution, (4) hepatic metabolism, and (5) renal tubular secretion. Absorption (unless active), filtration at the glomerulus, and passive tubular reabsorption would not be expected to exhibit racial differences. As is evident from this review, there are relatively few drugs for which there is information on ethnic or racial differences in pharmacokinetics. Thus it is often necessary to try to predict whether such differences might exist. Taking into consideration the above factors and evaluation of the pharmacokinetic characteristics of the drug, it should be possible to identify those drugs most likely to exhibit differences in their pharmacokinetics. For example, a drug which is eliminated entirely by the kidneys through filtration and reabsorption and is not highly bound to plasma proteins (or is bound to albumin) is highly unlikely to exhibit racial differences in its kinetics. Conversely, a drug which undergoes significant gut and/or hepatic first-pass metabolism and is highly bound to AGP is much more likely to exhibit kinetic differences between racial groups. A discussion of the impact of racial differences in kinetics on drug response or racial differences in drug efficacy, toxicity, or pharmacodynamics (concentration-response relationship) is beyond the scope of this review. However, a number of the papers described above also evaluated differences in pharmacodynamics or response. Among the comparisons of Chinese and Caucasians, these include the papers on propranolol, morphine, nifedipine, triazolam, diazepam, and omeprazole. For those studies comparing differences in blacks and Caucasians, responses or pharmacodynamics were also determined in the studies of propranolol, trimazosin, and methylprednisolone. Interested readers are also referred to the review by Wood and a more recent review by Kitler for additional discussion of ethnic/racial differences in pharmacodynamics/drug response.
Biological Availability↗
Recurrent vancomycin-resistant Enterococcus faecium bacteremia in a leukemia patient who was persistently colonized with vancomycin-resistant enterococci for two years.
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Adult↗