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Biomedical subjects

J R Sorenson

Publications and source records attributed to J R Sorenson.

At least 19 recordsLinked to original sources

Assessment of a decision aid to assist genetic testing research participants in the informed consent process.

Limited attention has been given to applying decision-making theories from psychology to the content and process of informed consent in genetic testing research. Data are presented from a study that developed and assessed a psychological theory-based decision aid as part of the informed consent process. This innovative approach assisted at-risk women in assessing the consequences of participating in a research project that offered them free hemophilia A genetic carrier testing. Results suggest: (1) the decision aid can be incorporated into the consent process with few problems; (2) women of varying educational backgrounds can complete the decision aid; (3) while women consider many consequences of genetic testing, their primary focus is on the implications for their family; and (4) this is in marked contrast to the typical benefit-harm statements prepared by researchers for genetic testing.

Consent Forms↗

Prion diseases: copper deficiency states associated with impaired nitrogen monoxide or carbon monoxide transduction and translocation.

Literature concerning prion diseases and Cu metabolism was examined to determine merits of various suggestions concerning the relationship between these diseases and altered Cu metabolism. There are a number of recent suggestions that the normal non-pathogenic form of the prion protein (PrP(C)) contains Cu while the abnormal pathogenic form of this protein, PrP(SC), lacks Cu. Results of experiments showing oxidant sensitivity in the presence of ionically bonded Cu and millimolar concentrations of hydrogen peroxide were found to lack relevance. Demonstrating superoxide disproportionation and a correlation with cellular Cu2Zn2SOD activity is relevant and consistent with a role for PrP(C) in Cu endocytosis. There are also a number of recent suggestions that PrP(C) has a role in nerve transmission. Serum from mice that lack cellular PrP(C) was found to have an elevated Cu content consistent with a response to overcome an inflammatory disease. Attempts to induce a 'transmissible' form of prion disease requiring intracerebral injections of somewhat purified brain homogenates were found lacking in support for an etiology occurring as the result of oral ingestion of supposedly 'infected' tissues. It is suggested that PrP(C) is a normal Cu-dependent cuproglycoprotein of unknown function that may have a role in facilitating normal nitrogen monoxide- or carbon monoxide-mediated biochemistry.

Animals↗

When the perpetrator gets killed: effects of observing the death of a handgun user in a televised public service announcement.

This study evaluates the cognitive effects of an anti-handgun violence public service announcement (PSA) on sixth-, seventh-, and eighth-grade students (N = 294). Participants were randomly assigned to a treatment group, which viewed a PSA depicting the death of an aggressive handgun user, or a comparison group, which viewed identical content except that the PSA showed no negative consequence for the handgun user. Logistic regression analysis, adjusting for race and gender, revealed that the treatment group was more likely to report negative expected outcomes for aggressively using a handgun and lower behavioral intentions to aggressively use a handgun compared with the comparison group. These findings suggest that observing handgun violence on television that depicts death as a negative physical consequence for the perpetrator may produce lower handgun-encouraging beliefs compared with observing no consequence for the perpetrator--the norm for most televised violence today.

Adolescent↗

Low-temperature crystal structures of tetrakis-mu-3,5-diisopropylsalicylatobis-dimethylformamidodico pper(II) and tetrakis-mu-3,5-diisopropylsalicylatobis-diethyletheratodicopp er(II) and their role in modulating polymorphonuclear leukocyte activity in overcoming seizures.

Two binuclear copper(II) complexes of 3,5-diisopropylsalicylic acid were characterized by single crystal X-ray diffraction methods and examined for anti-inflammatory activity using activated polymorphonuclear leukocytes and for anticonvulsant activities using electroshock and metrazol models of seizures. These complexes were crystallized from dimethylformamide (DMF) or diethylether. Tetrakis-mu-3,5-diisopropylsalicylatobis-dimethylformamidodicop per(II) [Cu(II)2(3,5-DIPS)4(DMF)2] I is in space group P 1; a = 10.393 (2), b = 11.258 (2), c = 12.734 (2) A, alpha = 96.64 (2), beta = 92.95 (2), gamma = 94.90 (2) degrees; V = 1471.7 (4) A3; Z = 1. Tetrakis-mu-3,5-diisopropylsalicylatobis-etheratodicopper(II ) [Cu(II)2(3,5-DIPS)4(ether)2] II is in space group P 1; a = 10.409 (3), b = 11.901 (4), c = 12.687 (6) A, alpha = 91.12 (5), beta = 90.84 (5), gamma = 100.90 (4) degrees; V = 1542 (1) A3; Z = 1. The structure of I was determined at 140 K from 4361 unique reflections (I > 2sigma(1)) and refined on F2 to R1 = 0.04 and wR2 = 0.09. The structure of II was determined at 180 K from 4605 unique reflections (I > 2sigma(I)) and refined on F2 to R1 = 0.05 and wR2 = 0.13. Each compound is a crystallographically centrosymmetric binuclear complex with Cu atoms bridged by four 3,5-diisopropylsalicylate ligands related by a symmetry center [Cu-Cu(i): 2.6139 (9) A in I and 2.613 (1) in II]. The four nearest O atoms around each Cu atom form a nearly rectangular planar arrangement with the square pyramidal coordination completed by the dimethylformamide (or diethylether) oxygen atom occupying an apical position, at a distance of 2.129 (2) A in I and 2.230 (3) A in II. Each Cu atom is displaced towards the DMF (or diethylether) ligand, by 0.189 A in I and 0.184 A in II, from the plane of the four O atoms. The crystal structures of I and II are essentially similar to each other, except for the DMF or diethylether accommodation. Many disorder phenomena were found in the crystal structure of I. Copper(II)2(3,5-DIPS)4(DMF)2 inhibited polymorphonuclear leukocyte (PMNL) oxidative metabolism in vitro. This effect was concentration related and significant for concentrations higher than 10 microg or 0.68 nmol/ml. Copper(II)2(3,5-DIPS)4(DMF)2 was more active than the parent ligand, 3,5-DIPS, as has been demonstrated with copper complexes of other non-steroidal anti-inflammatory drugs. The DMF and diethylether ternary complexes of Cu(II)2(3,5-DIPS)4 were found to have anticonvulsant activity in the maximal electroshock model of grand mal epilepsy in doses ranging from 26 to 258 micromol/kg of body mass following intraperitoneal, subcutaneous, or oral treatment. The DMF ternary complex was also found to be effective in the subcutaneous injection of metrazol model of petit mal epilepsy. We conclude that both ternary copper complexes are lipophilic and bioavailable, capable of facilitating the inflammatory response to brain injury and causing the subsidence of this response in bringing about remission of these disease states.

Animals↗

Crystal structure of 180 degree K of bis-3, 5-diisopropylsalicylatobisdimethylsulfoxidozinc(II) and the inhibition of seizures and polymorphonuclear leukocyte chemiluminescence.

Dimethylsulfoxide (DMSO) formed a ternary complex when mixed with a Zn-3, 5-diisopropylsalicylate complex of unknown structure. The structure of this new ternary complex was characterized in an initial effort to understand the nature of this compound. Since the original complex is known to have anticonvulsant activity, the new ternary complex was also examined for anticonvulsant activity. The original complex was examined for inhibition of the polymorphonuclear leukocyte (PMNL) respiratory burst in an effort to mechanistically account for zinc complex mediated anticonvulsant activity. Dissolving the structurally unknown complex in DMSO gave crystals of a characterizable complex with an empirical formula C30H46O8S2Zn. Crystallographic data: P 1, Z = 2, a = 8.06(1), b = 12.452(2), c = 17.951(2) A, alpha = 74.42(l), beta = 77.07(1), gamma = 89.50(1) degree. The structure was refined to R = 0.03, RW = 0.04 for 3815 independent reflections with I > 2 sigma(I). This complex is mononuclear, with two 3,5-diisopropylsalicylate ligands and two bonded DMSO ligands, Zn(II)(3,5-DIPS)2(DMSO)2, Zn(II) is coordinate covalently bonded to four O atoms in a strongly distorted tetrahedral arrangement. Each DMSO ligates via its sulfoxide O atom while each 3,5-diisopropylsalicylate ligand is monodentate The non-ligating carbonyl O atom of each 3,5-DIPS is free except for an intramolecular hydrogen bond from the hydroxy group of the same ligand. Both 3,5-DIPS acid and Zn(II)(3,5-DIPS)2(DMSO)2 were examined for anticonvulsant activity in the Maximal Electroshock (MES) and Metrazol (MET) models of seizures and found to prevent both types of seizures. The Zn complex was qualitatively and quantitatively more effective than treatment with the free ligand. The influence of a Zn 3,5-DIPS complex and of the ligand 3,5-DIPS on PMNL oxidative metabolism was also studied to help understand the mechanism of anticonvulsant activity of these compounds. A dose-related and significant decrease in chemiluminescent (CL) response to opsonized Zymosan was observed, and the Zn complex was significantly more effective than the free ligand. It is concluded that mononuclear Zn complexes have anticonvulsant activity in Grand Mal and Petit Mal models of seizure possibly due to inhibition of the synthesis of superoxide or down-regulation of Nitric Oxide Synthase in activated phagocytic cells of the central nervous system.

Animals↗

Interaction of Cu(II) 3,5-diisopropylsalicylate with human serum albumin--an evaluation of spectroscopic data.

The copper(II) complex of 3,5-diisopropylsalicylate is a lipophilic water-insoluble binuclear complex, Cu(II)2(3,5-DIPS)4, that has attracted interest because of a wide range of pharmacological activities. This study was undertaken to examine bonding interactions between the complex and human serum albumin (HSA) to help elucidate the mode of transport of the complex in vivo. Electron paramagnetic resonance, numerical magnetic resonance and UV-visible absorption spectroscopic studies were performed using 200 microM aqueous solutions (pH 7.5) of HSA to which had been added up to three molar equivalents of CuCl2, CuSO4, or Cu(II)2(3,5-DIPS)4. Both EPR and UV-visible spectra demonstrated the presence of more than one copper bonding site on HSA, and proton NMR spectra showed that the 3,5-DIPS ligand is also bonded to HSA. These results indicate that there is no observable direct coordination of the ligand to copper in the presence of HSA, and that the majority of the copper and 3,5-DIPS bond to HSA at separate sites. Addition of solid Cu(II)2(3,5-DIPS)4 to HSA at pH 7.5 similarly resulted in spectra suggest that there are no ternary Cu(II)(3,5-DIPS), Cu(II)(3,5-DIPS)2, or Cu(II)2(3,5-DIPS)4 complexes formed with HSA. It is concluded that any ternary complexes formed in the presence of HSA are below the spectroscopic detection limits and represent less than 5% of the total copper.

Electron Spin Resonance Spectroscopy↗

Acceptance of home and clinic-based cystic fibrosis carrier education and testing by first, second, and third degree relatives of cystic fibrosis patients.

We contacted and offered free cystic fibrosis (CF) carrier education and testing to the first, second, and third degree relatives of individuals with CF followed at a large Southeastern US CF Clinic. Relatives were offered CF carrier education and testing either in their homes or in a genetic counseling clinic. Overall, of 514 relatives offered free CF carrier education and testing, 299 (58%) accepted. Significantly more (67%) of those offered education and testing in their homes accepted than those offered education and testing in a genetic counseling clinic (45%). Regression analyses identified several factors, including education, income, gender, perceived chance of being a carrier, and perceived chance of having a child who is a CF carrier, as predictors of acceptance of education and testing in both home and clinic sites. A smaller set of factors was identified that predicted acceptance of education and testing unique to each site. Within the limits of this study and its design, even when CF carrier testing is offered free of charge, including education and testing in the home, acceptance of education and testing, while higher than in general population samples, is not universal among at-risk relatives. Several factors which may have contributed to the observations reported in this study are discussed.

Adolescent↗

Proband and parent assistance in identifying relatives for cystic fibrosis carrier testing.

To identify, contact, and offer free cystic fibrosis (CF) carrier education, testing, and genetic counseling to the first, second, and third degree relatives of individuals with CF, study personnel contacted probands or the parents of minor probands requesting assistance in identifying relatives. We requested family pedigrees, including names, addresses, and phone numbers and if necessary a saliva sample for determination of the specific CF mutations in the family. Two hundred three families of 220 probands being followed at a large CF clinic in the Southeastern United States were eligible for inclusion in the study. Of the 203 families 109 (53.7%) assisted by providing contact information on relatives and, when necessary, a saliva sample for mutation analysis. An additional 33 (16.4%) agreed to assist but did not provide either or both contact information or saliva samples. Sixty-one (30.1%) declined to provide assistance. Thirteen percent of the probands/parents wanted to talk with relatives before providing contact information. A logistic regression model predicting proband/parent assistance is provided. This study suggests that the active outreach method used here to identify at risk relatives to offer them CF carrier testing resulted in somewhat lower proband or parent assistance than reported by other similar approaches. The strengths and weaknesses of this approach, including comments by probands and parents on the method, are discussed.

Adolescent↗

Down-regulation of NADPH-diaphorase (nitric oxide synthase) may account for the pharmacological activities of Cu(II)2 (3,5-diisopropylsalicylate)4.

Purposes of this work were to develop an enzyme system as an in vitro model of the NADPH-dependent component of nitric oxide synthase (NOS) and examine the plausible down-regulation of this system and brain NOS by copper (II)2(3,5-diisopropylsalicylate)4[Cu(II)2(3,5-DIPS)4] as a mechanism accounting for its analgesic, anticonvulsant, and other pharmacological activities. Porcine heart diaphorase (PHD) was found to oxidize 114 microM NADPH with the corresponding reduction of an equivalent amount of 2,6-dichlorophenolindophenol (DCPIP). Addition of Cu(II)2(3,5-DIPS)4 to the reaction mixture decreased the reduction of DCPIP without substantially affecting the oxidation of NADPH. The IC50 for Cu(II)2(3,5-DIPS)4 in inhibiting the reduction of DCPIP was 1.5 microM. Mechanistically, this inhibition of DCPIP reduction was found to be due to the ability of Cu(II)2(3,5-DIPS)4 to serve as a catalytic electron acceptor for reduced PHD, which was enhanced by the presence of a large concentration of DCPIP and inhibited by a large concentration of NADPH. Oxidation of NADPH by PHD in the absence of DCPIP was linearly related to the concentration of Cu(II)2(3,5-DIPS)4 through the concentration range of 5-25 microM Cu(II)2(3,5-DIPS)4 with 50% recovery of NADPH oxidation by PHD at a concentration of 16 microM Cu(II)2(3,5-DIPS)4. Whole rat brain tissue sections incubated in medium containing an NADPH-generating system and nitroblue tetrazolium chloride (NBT) were less intensely stained when Cu(II)2(3,5-DIPS)4 was added to the medium. It is concluded that Cu(II)2(3,5-DIPS)4 serves as an electron acceptor in down-regulating PHD reduction of DCPIP and in down-regulating NOS in brain tissue sections. A decrease in NO synthesis in animal models of seizure, pain, and other disease states with Cu(II)2(3,5-DIPS)4 may account for the anticonvulsant, analgesic, and other pharmacological activities of this complex.

Animals↗

Modulation of polymorphonuclear leukocyte responsiveness by copper (II)2 (niflumate)4.

Antiinflammatory activities and modulations of PMNL responses produced by treatment with tetrakis-mu-2-[3-(trifluoromethyl)-phenyl]aminonicotinatodicopper (II) [Cu(II)2(niflumate)4] and niflumic acid were studied in isologous serum-induced rat pleurisy. Doses of 10 or 30 mg/kg (35 or 106 mumol/kg) of niflumic acid or Cu(II)2(niflumate)4 (8 or 23 mumol/kg) caused significant (p < 0.01) reductions in pleural exudate and number of polymorphonuclear leukocytes (PMNLs) in the exudate. While both doses of Cu(II)2(niflumate)4 produced significant dose-related reductions in both parameters, only the higher dose of niflumic acid produced a significant dose-related reduction in both parameters. Boyden chamber measurements of N-formyl-methionyl-leucyl-phenylalanine (f-MLP) chemotaxis by PMNLs incubated with 10 or 30 micrograms/ml niflumic acid (35 or 106 nmol/ml) or Cu(II)2(niflumate)4 (8 or 23 nmol/ml) were significantly (p < 0.01 to p < 0.001) decreased in dose-related fashions. Chemotaxis of PMNLs from pleuritic rats treated orally with 10 or 30 mg/kg niflumic acid or Cu(II)2(niflumate)4 was significantly (p < 0.001) inhibited by the larger dose of niflumic acid and both doses of Cu(II)2(niflumate)4. Opsonized zymosan (OZ)-stimulated chemiluminescence (CL) of PMNLs from pleuritic rats treated orally with these same doses of niflumic acid or Cu(II)2(niflumate)4 was only significantly (p < 0.05 or p < 0.01 respectively) decreased by the larger doses. Superoxide (O2-) production by these cells was significantly decreased by the larger dose of niflumic acid (p < 0.05) while both doses of Cu(II)2(niflumate)4 produced significant (p < 0.05 to p < 0.01) decreases.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Breast-feeding education of obstetrics-gynecology residents and practitioners.

OBJECTIVE: Our purpose was to assess breast-feeding education, knowledge, attitudes, and practices among resident and practicing obstetrician-gynecologists. STUDY DESIGN: A mailed survey was administered to a national sample of resident and practicing obstetrician-gynecologists. RESULTS: Response rates were 64% for residents and 69% for practitioners. Residency training included limited opportunity for direct patient interaction regarding breast-feeding; 60% of practitioners recommended that training devote more time to breast-feeding counseling skills. Only 38% of residents reported that obstetric faculty presented breast-feeding topics; more common sources were nursing staff and other residents. Practitioners rated themselves as more effective in meeting the needs of breast-feeding patients than were residents; prior personal breast-feeding experience was a significant influence on perceived effectiveness. Almost all respondents agreed that obstretician-gynecologists have a role in breast-feeding promotion, but significant deficits in knowledge of breast-feeding benefits and clinical management were found. CONCLUSION: Residency training and continuing education programs should create opportunities to practice breast-feeding promotion skills and emphasize management of common lactation problems.

Breast Feeding↗

Increasing Medicaid child health screenings: the effectiveness of mailed pamphlets, phone calls, and home visits.

OBJECTIVES: A randomized controlled trial was conducted to test the effectiveness and cost effectiveness of three outreach interventions to promote well-child screening for children on Medicaid. METHODS: In rural North Carolina, a random sample of 2053 families with children due or overdue for screening was stratified according to the presence of a home phone. Families were randomly assigned to receive a mailed pamphlet and letter, a phone call, or a home visit outreach intervention, or the usual (control) method of informing at Medicaid intake. RESULTS: All interventions produced more screenings than the control method, but increases were significant only for families with phones. Among families with phones, a home visit was the most effective intervention but a phone call was the most cost-effective. However, absolute rates of effectiveness were low, and incremental costs per effect were high. CONCLUSIONS: Pamphlets, phone calls, and home visits by nurses were minimally effective for increasing well-child screenings. Alternate outreach methods are needed, especially for families without phones.

Adult↗

Radiation protection and radiation recovery with essential metalloelement chelates.

Understanding essential metalloelement metabolism and its role in tissue maintenance and function, as well as the roles of essential metalloelement-dependent enzymes in responding to injury, offer a new approach to decreasing and/or treating radiation injury. This review presents the roles of some essential metalloelement-dependent enzymes in tissue maintenance and function, and their responses to radiation injury in accounting for radiation protection and recovery effects observed for nontoxic doses of essential metalloelement compounds. Effects of biochemicals including water undergoing bond radiolysis and the effects of free radicals derived from diatomic oxygen account for the acute and chronic aspects of radiation injury. Recognized biochemical roles of essential metalloelement-dependent enzymes and the observed pharmacological effects of small-molecular mass chelates predict the therapeutic usefulness of essential metalloelement complexes in decreasing and/or treatment of radiation injury. Copper chelates have radiation protection and radiation recovery activities and cause rapid recovery of immunocompetency and recovery from radiation-induced histopathology. Mice treated with Cu(II)2(3,5-diisopropylsalicylate)4[Cu (II)2(3,5-DIPS)4] had increased survival and corresponding increases in numbers of myeloid and multipotential progenitor cells early after irradiation and earlier recovery of immune reactivity. Examination of radiation-induced histopathology in spleen, bone marrow, thymus, and small intestine also revealed Cu(II)2(3,5-DIPS)4-mediated rapid recovery of radiation-induced histopathology. Most recently, Fe, Mn, and Zn complexes have also been found to prevent death in lethally irradiated mice. These pharmacological effects of essential metalloelement chelates can be understood as due to facilitation of de novo synthesis of essential metalloelement-dependent enzymes which have roles in preventing the accumulation of pathological concentrations of oxygen radicals or repairing biochemical damage caused by radiation-induced bond homolysis. Essential metalloelement chelates offer a physiological approach to prevention and/or treatment of radiation injury.

Animals↗

Pediatrician involvement in breast-feeding promotion: a national study of residents and practitioners.

OBJECTIVE: Physician support for breast-feeding mothers has been shown to improve breast-feeding rates, but no evaluation of the adequacy of physicians' breast-feeding-related training has been conducted. This study was designed to assess pediatricians' knowledge, attitudes, training, and activities related to breast-feeding promotion. METHODS: Surveys were mailed to a national random sample of pediatric residents (n = 999) and practitioners (n = 610) who were board certified within the previous 3 to 5 years. RESULTS: Response rates were 74% for residents and 69% for practitioners. Although more than 90% of respondents agreed that pediatricians should be involved in breast-feeding promotion, their clinical knowledge and experience did not suggest a high degree of competency. For example, practitioners were only slightly more aware of breast-feeding's protective effect against otitis media (71% vs 60%), and more than one quarter of both groups did not agree that exclusive breast-feeding is the most beneficial form of infant nutrition. Clinical advice often included inappropriate recommendations for breast-feeding termination or formula supplementation; only 64% of practitioners and 52% of residents knew that supplementing during the first few weeks of life may cause breast-feeding failure. For both groups, prior personal breast-feeding experience (ie, respondent or spouse had breast-fed an infant for 2 or more weeks) was a major determinant of improved clinical knowledge, more frequent activity, and greater self-confidence and perceived effectiveness in the area of breast-feeding promotion. Residents reported that the breast-feeding instruction provided during training was primarily in lecture format, with limited clinical opportunities to practice skills needed to assist breast-feeding mothers. Reflecting on their own training, more than 70% of practitioners recommended that more time be devoted to direct patient interaction and practice of counseling and problem-solving skills. CONCLUSIONS: These results indicate that residency training does not adequately prepare pediatricians for their role in breast-feeding promotion. Improvements in residency training and innovative continuing education programs should be implemented to help pediatricians meet the needs of their breast-feeding patients.

Breast Feeding↗

Breast-feeding education and practice in family medicine.

BACKGROUND: Physician support has been shown to increase breast-feeding rates, but anecdotal reports suggest that physicians are ill prepared for their role in breast-feeding promotion. Inadequate breast-feeding education during residency training may be a contributing factor. METHODS: A self-administered questionnaire mailed to 1099 family medicine residents and 665 recently board-certified family physicians assessed knowledge, attitudes, education, and activity related to breast-feeding promotion. Response rates were 71% for residents and 58% for physicians. RESULTS: Although residents and physicians were strongly convinced that family physicians should be involved in breast-feeding promotion, both groups demonstrated significant deficits in knowledge about breast-feeding benefits and clinical management strategies. Common errors included inappropriate recommendations for breast-feeding termination or formula supplementation, a proven cause of breast-feeding failure. Personal breast-feeding experience was the only factor consistently associated with more frequent breast-feeding promotion activity among residents and increased self-confidence for both groups. Respondents reported only limited opportunities for developing breast-feeding counseling skills during residency training. CONCLUSIONS: Improved breast-feeding education is needed for family medicine residents and physicians. Residency training and continuing education programs should emphasize the benefits of breast-feeding, clinical management strategies, and development of practical counseling skills.

Breast Feeding↗