ABSTRACT
We investigated whether disclosure of coronary heart disease (CHD) genetic risk influences perceived personal control (PPC) and genetic counseling satisfaction (GCS). Participants (n = 207, age: 45-65 years) were randomized to receive estimated 10-year risk of CHD based on a conventional risk score (CRS) with or without a genetic risk score (GRS). Risk estimates were disclosed by a genetic counselor who also reviewed how GRS altered risk in those randomized to CRS+GRS. Each participant subsequently met with a physician and then completed surveys to assess PPC and GCS. Participants who received CRS+GRS had higher PPC than those who received CRS alone although the absolute difference was small (25.2 ± 2.7 vs 24.1 ± 3.8, p = 0.04). A greater proportion of CRS+GRS participants had higher GCS scores (17.3 ± 5.3 vs 15.9 ± 6.3, p = 0.06). In the CRS+GRS group, PPC and GCS scores were not correlated with GRS. Within both groups, PPC and GCS scores were similar in patients with or without family history (p = NS). In conclusion, patients who received their genetic risk of CHD had higher PPC and tended to have higher GCS. Our findings suggest that disclosure of genetic risk of CHD together with conventional risk estimates is appreciated by patients. Whether this results in improved outcomes needs additional investigation.
Subject(s)
Coronary Artery Disease/genetics , Genetic Counseling , Genetic Predisposition to Disease , Personal Satisfaction , Female , Humans , Male , Middle Aged , Risk Factors , Surveys and QuestionnairesABSTRACT
Although the integration of whole genome sequencing (WGS) into standard medical practice is rapidly becoming feasible, physicians may be unprepared to use it. Primary care physicians (PCPs) and cardiologists enrolled in a randomized clinical trial of WGS received genomics education before completing semi-structured interviews. Themes about preparedness were identified in transcripts through team-based consensus-coding. Data from 11 PCPs and 9 cardiologists suggested that physicians enrolled in the trial primarily to prepare themselves for widespread use of WGS in the future. PCPs were concerned about their general genomic knowledge, while cardiologists were concerned about how to interpret specific types of results and secondary findings. Both cohorts anticipated preparing extensively before disclosing results to patients by using educational resources with which they were already familiar, and both cohorts anticipated making referrals to genetics specialists as needed. A lack of laboratory guidance, time pressures, and a lack of standards contributed to feeling unprepared. Physicians had specialty-specific concerns about their preparedness to use WGS. Findings identify specific policy changes that could help physicians feel more prepared, and highlight how providers of all types will need to become familiar with interpreting WGS results.
Subject(s)
Genome, Human , Physicians , Sequence Analysis, DNA/methods , Adult , Aged , Female , Humans , Male , Middle Aged , MotivationABSTRACT
We evaluated virtual crossmatching (VXM) for organ allocation and immunologic risk reduction in sensitized isolated intestinal transplantation recipients. All isolated intestine transplants performed at our institution from 2008 to 2011 were included in this study. Allograft allocation in sensitized recipients was based on the results of a VXM, in which the donor-specific antibody (DSA) was prospectively evaluated with the use of single-antigen assays. A total of 42 isolated intestine transplants (13 pediatric and 29 adult) were performed during this time period, with a median follow-up of 20 months (6-40 months). A sensitized (PRA ≥ 20%) group (n = 15) was compared to a control (PRA < 20%) group (n = 27) to evaluate the efficacy of VXM. With the use of VXM, 80% (12/15) of the sensitized patients were transplanted with a negative or weakly positive flow-cytometry crossmatch and 86.7% (13/15) with zero or only low-titer (≤ 1:16) DSA. Outcomes were comparable between sensitized and control recipients, including 1-year freedom from rejection (53.3% and 66.7% respectively, p = 0.367), 1-year patient survival (73.3% and 88.9% respectively, p = 0.197) and 1-year graft survival (66.7% and 85.2% respectively, p = 0.167). In conclusion, a VXM strategy to optimize organ allocation enables sensitized patients to successfully undergo isolated intestinal transplantation with acceptable short-term outcomes.
Subject(s)
Graft Rejection/immunology , Graft Rejection/prevention & control , Histocompatibility Testing/methods , Intestines/transplantation , Organ Transplantation/methods , Transplantation , Adult , Child , Child, Preschool , Cold Ischemia , Female , Follow-Up Studies , Humans , Immunoassay , Male , Middle Aged , Prospective Studies , Retrospective Studies , Risk Factors , Transplantation, Homologous , Treatment Outcome , Waiting ListsABSTRACT
Susceptibility testing for common, complex adult-onset diseases is projected to become more commonplace as the rapid pace of genomic discoveries continues, and evidence regarding the potential benefits and harms of such testing is needed to inform medical practice and health policy. Apolipoprotein E (APOE) testing for risk of Alzheimer's disease (AD) provides a paradigm in which to examine the process and impact of disclosing genetic susceptibility for a prevalent, severe and incurable neurological condition. This review summarizes findings from a series of multi-site randomized clinical trials examining psychological and behavioral responses to various methods of genetic risk assessment for AD using APOE disclosure. We discuss challenges involved in disease risk estimation and communication and the extent to which participants comprehend and perceive utility in their genetic risk information. Findings on the psychological impact of test results are presented (e.g. distress), along with data on participants' health behavior and insurance purchasing responses (e.g. long-term care). Finally, we report comparisons of the safety and efficacy of intensive genetic counseling approaches to briefer models that emphasize streamlined processes and educational materials. The implications of these findings for the emerging field of personal genomics are discussed, with directions identified for future research.
Subject(s)
Alzheimer Disease/genetics , Genetic Predisposition to Disease , Adult , Apolipoproteins E/genetics , Female , Genetic Counseling , Genetic Predisposition to Disease/psychology , Genetic Testing , Humans , Insurance, Long-Term Care/economics , Life Style , Male , Mental Recall , Randomized Controlled Trials as Topic , Risk AssessmentABSTRACT
AIM: This study examined understandings of basic genetic concepts among Americans. METHOD: In a national telephone survey of 1,200 Americans with equal representation among Black and White men and women, subjects responded to 8 items developed by a multidisciplinary team of experts that assessed understanding of basic concepts in multiple domains, including inheritance, genetics and race, and genetics and behavior. RESULTS: Over 70% of subjects responded correctly on items about the genetic similarity of identical twins and siblings. Less than half of subjects responded correctly on all other items. Understanding of genetics was lowest in three areas: types/locations of genes in the body (29% correct), a genetic basis for race (25% correct), and the influence of single genes on behaviors (24% correct). Logistic regression models controlling for age and education showed some differences by race and gender on specific items but also showed that understandings are generally similar across these groups. CONCLUSION: Misunderstandings about genetics are common among Black and White American men and women. Responses appear to reflect personal experiences, group values and interests. These findings emphasize the need for initiatives to improve the public's genetic literacy as well as a need for further investigation in this domain.
Subject(s)
Black People , Genetic Predisposition to Disease , Genetics, Medical , Health Knowledge, Attitudes, Practice , Inheritance Patterns , White People , Adolescent , Adult , Aged , Aged, 80 and over , Educational Status , Female , Gene Expression , Humans , Male , Middle Aged , Risk Factors , Young AdultABSTRACT
Two experiments were conducted to determine whether supplemental levels of L-proline in the diets of broiler chickens would mitigate the skin weakening effect caused by continuous feeding of the anticoccidial halofuginone. In Experiment 1, tensile strength and collagen levels in thigh apteria skin were determined at 21 and 42 d of age in male broilers fed 0, .5, and 1% L-proline with either halofuginone (3 mg/kg) or salinomycin (61 mg/kg). In Experiment 2, the same measurements were made on female broilers receiving diets containing halofuginone and supplemented with 0, .5, or 1% L-proline, 1% L-proline through 21 d of age, or 1% L-glutamic acid through 21 d of age, or a diet containing high L-proline feedstuffs (corn gluten meal and ring dried blood meal). In Experiment 1, dermis thickness of thigh apteria was measured in the males at Day 21. Skin strength was increased in male and female broilers fed halofuginone with addition of .5 and 1% L-proline, respectively, at 21 and 42 d of age. Continuous incorporation of synthetic L-proline into diets was shown to improve skin strength in females, whereas diets formulated to contain high levels of L-proline from feedstuffs, 21-d feeding of L-proline, or L-glutamic acid did not increase skin strength.
Subject(s)
Chickens , Coccidiostats/adverse effects , Food, Fortified , Proline/pharmacology , Quinazolines/adverse effects , Skin/drug effects , Tensile Strength/drug effects , Animals , Body Weight/drug effects , Coccidiostats/administration & dosage , Collagen/drug effects , Collagen/metabolism , Female , Male , Piperidines , Proline/administration & dosage , Quinazolines/administration & dosage , Quinazolinones , Skin/metabolism , Skin Physiological PhenomenaABSTRACT
Two experiments were conducted to evaluate dietary and environmental factors involved in skin tensile strength of commercial broilers. In Experiment 1 the effect of added dietary fat (4 or 7%), environmental temperature (25 or 20.5 C after 21 d), and anticoccidial drug (halofuginone or salinomycin fed continuously) were examined factorially using male and female chicks. Skin tensile strength was measured at 21, 35, and 40 d of age. Thickness of the dermal layers was measured from skin taken at Day 35. In Experiment 2, the effect of added dietary fat (0 or 7%), environmental temperature (25 or 18.5 C after 21 d), and anticoccidial drug (halofuginone or salinomycin) were examined factorially using female chicks. Skin strength and collagen content of the skin were measured at 21, 38, and 42 d of age. Skin tensile strength increased with age in both experiments, but female skin strength was subject to periodic decline. Males had significantly strong skin than females. Levels of added fat or environmental temperature did not affect skin strength in either experiment. Continuous feeding of halofuginone significantly (P < .0001) decreased skin strength compared with that of birds fed salinomycin in both experiments. Halofuginone reduced skin strength in females more than males (25 and 9%, respectively). Dermis thickness was correspondingly reduced in the birds consuming halofuginone. In Experiment 2, soluble collagen contents were reduced at all ages in birds consuming halofuginone; insoluble collagen was significantly decreased at 21 d of age. Birds with weakened skin exhibited increased incidence of skin tears during slaughter in a commercial processing plant (P < or = .0043). These results suggest that halofuginone interferes with collagen synthesis, causing decreased collagen formation and reduced skin strength. Neither added dietary fat nor ambient temperature were involved.
Subject(s)
Chickens/physiology , Coccidiostats/pharmacology , Dietary Fats/administration & dosage , Skin Physiological Phenomena , Temperature , Age Factors , Animals , Body Weight/drug effects , Chickens/anatomy & histology , Collagen/analysis , Eating/drug effects , Female , Male , Sex Factors , Skin/anatomy & histology , Skin/drug effects , Tensile Strength/drug effectsABSTRACT
Continuous feeding of the anticoccidial halofuginone to broilers is associated with reduced skin tensile strength and increased skin tearing during processing. The possible mitigating effect of shuttle administration of halofuginone and salinomycin to female broilers was evaluated. Halofuginone or salinomycin were included in the starter and grower diets in all four possible combinations, with anticoccidial omitted from the finisher diets. Starter, grower, and finisher diets were fed to broilers through 3, 6, and 7 wk of age, respectively. Skin strength of pullets fed a diet based on milo and corn (NW) vs a diet based on corn was also compared in a factorial arrangement. Two further treatments were also included: 1) halofuginone-only NW diet supplemented with 2,500 ppm ascorbic acid from 0 to 7 wk; and 2) NW diet reared on wire floor without anticoccidial treatment. Skin tensile strength was determined at 3, 6, and 7 wk of age. Dietary composition had no effect upon skin strength or BW of broilers. Addition of ascorbic acid to the diet containing halofuginone anticoccidial did not improve skin strength. Continuous feeding of halofuginone reduced skin strength whereas withholding anticoccidial and continuous feeding of salinomycin resulted in high skin strength. When halofuginone was used in shuttle feeding programs with salinomycin, there were no differences in skin strength at 7 wk of age compared to birds that were continuously treated with salinomycin. These results suggest halofuginone may be used in a shuttle program either during the starter or grower phase without adverse affect on skin tensile strength at slaughter.
Subject(s)
Chickens/physiology , Coccidiostats/administration & dosage , Quinazolines/administration & dosage , Skin Physiological Phenomena , Animal Feed , Animals , Diet/veterinary , Drug Administration Schedule/veterinary , Female , Piperidines , Pyrans/administration & dosage , Quinazolinones , Skin/drug effects , Tensile Strength/drug effectsABSTRACT
Three hundred and twenty-four samples from platelet concentrate bags were examined for bacterial contamination. Blood cultures were made when platelet transfusion was followed by pyrexia to examine the frequency of platelet transfusion-induced septicemia. 6.5% of samples showed bacterial growth, mostly ordinary skin flora, but other bacteria were also demonstrated. Pyrexia followed 14% of the transfusion episodes, and in 58% of the febrile episodes this was associated with bacterial contamination of the bag. In one episode of post-transfusion pyrexia the same bacteria were found in cultures from both bag and blood. The case is presented here. Sources of bacterial contamination of platelet preparations are discussed. The use of platelet concentrates in treatment of thrombocytopenic patients is so important that the demonstrated rate of contamination does not alter the indication for platelet transfusion. Nevertheless, when platelet transfusion is followed by pyrexia, cultures from the bag and patient's blood should be performed to establish etiology and relevant antibiotic treatment.
Subject(s)
Bacteria/isolation & purification , Platelet Transfusion , Adult , Blood Platelets/microbiology , Blood Specimen Collection , Fever/microbiology , Humans , Male , Sepsis/microbiologyABSTRACT
Serum creatine kinase was assessed in 94 consecutive patients without convulsions admitted to hospital due to suspicion of infection of the central nervous system. No reliable discrimination between patients with aseptic and those with bacterial meningitis was obtained. Patients with bacterial meningitis and brain oedema, as well as patients with encephalitis, had significantly higher values (P less than 0.01) than patients with meningism, aseptic meningitis and bacterial meningitis without cerebral oedema. Very high values, above 2500 U/1, were encountered in only the most severe cases of bacterial meningitis. The highest serum CK value found in patients with encephalitis was 725 U/l. Reference values for control patients with meningism were 16-269 U/1. In a subset of 9 patients creatine kinase isoenzyme analysis was performed. In all cases only muscle type (MM) isoenzyme was found.
Subject(s)
Bacterial Infections/enzymology , Creatine Kinase/blood , Encephalitis/enzymology , Meningism/enzymology , Meningitis, Aseptic/enzymology , Meningitis/enzymology , Adolescent , Adult , Aged , Brain Edema/enzymology , Child , Child, Preschool , Female , Humans , Infant , Isoenzymes , Male , Middle AgedABSTRACT
In a double-blind randomised trial 40 patients above 60 years old with acute herpes zoster received either 5 mg/kg acyclovir three times daily intravenously or 400 mg acyclovir five times daily orally for five days. Identical results were obtained with respect to duration of pain and rate of healing. Twenty per cent of orally administered acyclovir was absorbed and gave satisfactory concentrations of acyclovir in the vesicular fluid.
Subject(s)
Acyclovir/administration & dosage , Herpes Zoster/drug therapy , Acyclovir/therapeutic use , Acyclovir/urine , Administration, Oral , Aged , Clinical Trials as Topic , Double-Blind Method , Female , Humans , Injections, Intravenous , Male , Pain/etiology , Random AllocationABSTRACT
The T-cell mediated immunity in 21 patients with seronegative spondarthritis was tested with mitogens PHA, PWM, Con-A and MLC, and found to be reduced except when tested with Con-A. The patients were then treated with levamisole or placebo for 12 weeks in a double-blind trial. During treatment the T-cell responses normalized in both groups, and it is concluded that the enhanced response is independent of levamisole. Earlier we reported clinical improvement in levamisole treated patients and the data of the present study suggest that the effect of levamisole occurs locally in the inflamed tissues.
Subject(s)
Arthritis, Reactive/immunology , Levamisole/therapeutic use , Lymphocyte Activation , Spondylitis, Ankylosing/immunology , T-Lymphocytes/immunology , Adult , Arthritis, Reactive/drug therapy , Concanavalin A/pharmacology , Double-Blind Method , Female , Humans , Lymphocyte Culture Test, Mixed , Male , Middle Aged , Phytohemagglutinins/pharmacology , Pokeweed Mitogens/pharmacology , Spondylitis, Ankylosing/drug therapyABSTRACT
The present study describes the T lymphocytosis in infectious mononucleosis (IM), using rosette techniques, lymphocyte transformation tests, Con A suppressor tests, and chromosomal analysis. Blood was drawn from twelve patients with IM during acute illness and during convalescence. We found a T lymphocytosis with a normal sheep erythrocyte receptor affinity of T cells, using three different E-rosette techniques. The percentage of T cells with Fc receptors for IgM (T mu) was reduced during acute illness, but normal in convalescence. The percentage of T cells with Fc receptors for IgC (T gamma) was normal during illness and slightly reduced afterwards. Owing to the T lymphocytosis the total number of T gamma lymphocytes was significantly increased during IM. The lymphocyte reactivity in vitro after mitogen stimulation (PHA, Con A, PWM) was in the lower end of the normal range. We found no evidence of increased suppressor-cell activity activity during IM, using a Con A suppressor cell assay. No chromosomaL defects were observed in lymphocytes from blood.
Subject(s)
Infectious Mononucleosis/immunology , T-Lymphocytes/immunology , Adolescent , Adult , Convalescence , Female , Humans , Infectious Mononucleosis/genetics , Karyotyping , Leukocyte Count , Lymphocyte Activation , Male , Middle Aged , Phenotype , Rosette Formation , T-Lymphocytes/classificationABSTRACT
Immune complexes in serum, urinary excretion of albumin and beta-2-microglobulin were determined in patients with infectious mononucleosis, both during the acute stage of the disease and one month later. At the first examination immune complexes were detected in 8 out of 12 patients, using both the ClqBA and the PP-Lc methods, but had disappeared in all after one month. Urinary excretion was initially increased for albumin in one of 9 and for beta-2-microglobulin in 5 of 9 patients. A significant fall in excretion was noted for beta-2-microglobulin during the acute phase (0.486 to 0.190 ng/min (medians), p less than 0.01) whereas albumin excretion did not change significantly (9.0 to 4.0 micrograms/min). Excretions were normal in all patients after one month. The magnitude of proteinuria was not correlated to the serum level of immune complexes. Serum beta-2-microglobulin was initially increased in 8 of 9 patients, but normal after one month (3.8 to 2.2 mg/l, p less than 0.01). There was a significant correlation between levels of beta-2-microglobulin in serum and urine (rho = 0.833, n = 9, p less than 0.01). 51Cr-EDTA clearance was the same during the acute illness and one month later. It is concluded that the abnormalities in urinary protein excretion do not seem to be related to the presence of circulating immune complexes in infectious mononucleosis and that the elevated urinary beta-2-microglobulin excretion is most likely due to increase production.
Subject(s)
Albuminuria/immunology , Antigen-Antibody Complex/analysis , Beta-Globulins/urine , Infectious Mononucleosis/immunology , beta 2-Microglobulin/urine , Acute Disease , Adolescent , Adult , Albuminuria/complications , Edetic Acid , Glomerular Filtration Rate , Humans , Infectious Mononucleosis/complications , Infectious Mononucleosis/diagnosis , Male , beta 2-Microglobulin/analysisSubject(s)
Antimalarials/adverse effects , Pyrimethamine/adverse effects , Sulfadoxine/adverse effects , Sulfanilamides/adverse effects , Aged , Agranulocytosis/chemically induced , Drug Combinations/adverse effects , Female , Humans , Jaundice/chemically induced , Malaria/prevention & control , Male , Middle Aged , Photosensitivity Disorders/chemically induced , Stevens-Johnson Syndrome/etiologySubject(s)
Attitude of Health Personnel , Nurses , Physicians , Smoking Prevention , Denmark , Humans , Statistics as TopicABSTRACT
The effects of insulin on bile flow and composition were examined in fasting, chloralose-anesthetized cats. Insulin in doses from 0.01 to 2.00 U/kg increased bile flow and biliary erythritol clearance without any detectable change in the difference between them; thus insulin presumably had no effect on ductular fluid transport. Continuous infusion of insulin (0.8 U/kg+0.05 U/kg/min or 0.05 U/kg+0.002 U/kg/min) increased biliary erythritol clearance by 22%. The increase was caused by a rise in the bile acid-independent fraction of bile production and accompanied by a parallel increase in the rates of biliary excretion of Na+ and Cl-. When ouabain, 80 micrograms/kg, was injected intraportally during insulin infusion the erythritol clearance, bile flow and the rates of biliary excretion of Na+ and Cl- were lowered towards but not to their preinsulin levels. The effects of insulin on these parameters were unchanged after atropin or gastrectomy and 2-Deoxy-D-Glucose was without effect on bile production. The results indicate that administration of insulin affects bile formation by stimulating the active transport of sodium across the canalicular membrane.