Full remission of growth hormone (GH)-induced retinopathy after GH treatment discontinuation: long-term follow-up.
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Adult↗
Biomedical subjects
R Hansen
Publications and source records attributed to R Hansen.
Recombinant hirudin as an alternative for anticoagulation during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type II: a 1-year experience in 57 patients.
OBJECTIVE: To explore the possible use of recombinant hirudin (r-hirudin) as an alternative to heparin for anticoagulation during cardiovascular surgery. DESIGN: Retrospective analysis. SETTING: Two university hospitals. PARTICIPANTS: Fifty-seven patients with heparin-induced thrombocytopenia type II (HIT II) in whom r-hirudin was used during cardiovascular surgery with cardiopulmonary bypass (CPB). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The r-hirudin concentration was monitored on-line, at the point of the patient's care using the ecarin clotting time and maintained in the range of 3 to 4 microg/mL. The r-hirudin elimination at the conclusion of CPB was augmented through modified zero-balanced ultrafiltration and forced diuresis. The duration of CPB was 63 to 246 minutes. The r-hirudin requirement per minute of CPB was 0.016 to 0.035 microg/kg/min, and the 24-hour blood drainage was 50 to 2,200 mL. Of the 57 patients, 54 fully recovered, including 9 patients who did not require any allogenic products. Four patients, all with impaired renal function, showed prolonged r-hirudin elimination and excessive bleeding and required surgical reexploration. Three patients died as a result of complications unrelated to the perioperative management. CONCLUSION: This study provides evidence that r-hirudin can be used safely and effectively for routine anticoagulation during CPB in patients diagnosed with HIT II. Almost 95% of the patients in whom it was used were discharged uneventfully. Patients with perioperative renal failure, however, showed increased bleeding.
Adult↗
Hirudin monitoring using the TAS ecarin clotting time in patients with heparin-induced thrombocytopenia type II.
OBJECTIVE: To assess the reliability of the TAS/ecarin clotting time (ECT) for on-line monitoring of r-hirudin in cardiovascular surgery with and without cardiopulmonary bypass (CPB). DESIGN: Samples were spiked with r-hirudin (0 to 5 microg/mL) and calibration curves constructed. Reproducibility was evaluated by measurement of the sample five times at each concentration. The influence of variations in hematocrit, plasma factors, and platelet count on the test results was examined. Samples were obtained from patients during cardiovascular surgery with CPB (n = 8), without CPB (n = 3), and from volunteers (n = 5) and compared with the laboratory reference tests. All tests were performed in duplicate. SETTING: Deutsches Herzzentrum Berlin. PARTICIPANTS: Five healthy volunteers and 11 patients undergoing cardiovascular surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The TAS/ECT showed linearity and reliability to an r-hirudin concentration of 5 microg/mL and was not influenced (p < 0.005) by the varying conditions of the in vitro setup. The correlation to the laboratory method was 0.74 for the CPB group and 0.87 for the non-CPB group. CONCLUSIONS: The TAS/ECT is a reliable assay for monitoring r-hirudin at the point of care. With this information, the use of r-hirudin during surgery or angioplasty should become more effective and safer.
Adult↗
Physiological and cognitive performance of soldiers conducting routine patrol and reconnaissance operations in the tropics.
The physiological and cognitive performance of acclimatized soldiers undertaking routine patrol and reconnaissance activities in the tropics was investigated. Data were obtained during a patrol and a reconnaissance exercise followed by a short assault. Ambient conditions were characterized by temperatures of 30 to 33 degrees C, low humidity (52-59%), and moderate to high solar radiation. Maximum metabolic rates during patrol were high, although the equipment carried was modest and the terrain was not severe. Rectal temperatures peaked at 38.2 and 38.4 degrees C for patrol and assault activities, respectively; peak heart rates were 160 beats min-1 for each activity. Sweat rates of approximately 9 and 14 g kg-1 body weight h-1 were recorded for patrol and assault activities, respectively. The soldiers maintained adequate hydration levels and displayed no evidence of deterioration in cognitive performance. The data show that routine operational activities in tropical conditions induced physiological strain in acclimatized soldiers. However, this strain was not maintained at hazardous levels for lengthy periods.
Acclimatization↗
Cell ashing for trace element analysis: A new approach based on ultraviolet/ozone.
We studied a new approach to cell ashing based on illuminating the specimens with a low-pressure mercury discharge lamp. We analyzed with synchrotron spectromicroscopy its effects on different physiological elements in neurobiological specimens. Our results demonstrate that carbon is removed, whereas phosphorus, calcium, potassium, and sulfur are retained and their relative concentrations are enhanced. Applied to trace elements, this technique will enhance their practical detectability.
Animals↗
Nitric oxide diffusion across membrane lungs protects platelets during simulated extracorporeal circulation.
BACKGROUND: The absence of a protective endothelial surface on membrane oxygenators during extracorporeal circulation (ECC) promotes platelet trapping and damage, leading to increased bleeding complications. We investigated the effects of transmembranous diffusion of gaseous nitric oxide (NO) on platelets during simulated ECC. MATERIAL AND METHODS: Two paired circuits were run in parallel with fresh, heparinized (1 U mL-1) blood from healthy human donors for 240 min. To one of the paired circuits, 20 ppm NO was added transmembranously. RESULTS: NO significantly attenuated platelet trapping and reduced intracircuit platelet activation evaluated by the release of beta-thromboglobulin, platelet factor 4 and soluble P-selectin. Furthermore, NO significantly preserved platelet reactivity to stimulating agents (ADP and adrenaline), evaluated as the ability to expose P-selectins and activate glycoprotein (GP)-IIb-IIIa. Nevertheless, circulating activated platelets expressing P-selectin or activated GPIIb-IIIa were not different and were not significantly increased. The mean fluorescence intensity of GPIb and GPIIb-IIIa decreased in both circuits equally. CONCLUSIONS: Transmembranous diffusion of gaseous NO revealed protective effects on platelets by reducing thrombocytopenia/pathia and preserving platelet reactivity.
Adenosine Diphosphate↗
Diagnostic accuracy and image quality using a digital camera for teledermatology.
OBJECTIVE: The study was designed to evaluate the effectiveness of digital photography for dermatologic diagnoses and compare it with in-person diagnoses. MATERIALS AND METHODS: Patients referred for specialty consultations (n = 308) were recruited from a university dermatology clinic. Patients were examined in-person by one of three board-certified dermatologists who provided clinical diagnoses. Digital photos were obtained on all patients and were evaluated as computer images by a panel of dermatologists. RESULTS: There was 83% concordance between in-person versus digital photo diagnoses. Intradermatologist concordance averaged 84%, and interdermatologist concordance averaged 81%. Decision confidence was rated as "very definite" to "definite" 62% of the time. Concordance with biopsy results was achieved in 76% of the cases. Image sharpness and color quality were rated "good" to "excellent" 83% and 93% of the time, respectively. CONCLUSION: Digital photography for store-and-forward teledermatology produces high-quality images and diagnostic concordance rates that compare favorably with in-person clinical diagnoses.
Arizona↗
Quantitative detection of porcine interferon-gamma in response to mitogen, superantigen and recall viral antigen.
Five monoclonal antibodies (mAbs) specific for porcine interferon-gamma (PoIFN-gamma) were isolated and utilized to develop a PoIFN-gamma sandwich ELISA. Specific reactivity of each mAb with E. coli derived recombinant PoIFN-gamma, but not with rPoIL-2 or rPolL-10, was confirmed in an indirect ELISA and in Western blots. Competitive ELISAs showed that mAbs P2A4 and P2C11 bound an epitope which was not recognized by mAbs P2G10, P1B7 or P2F6. The latter three mAbs were able to neutralize the ability of natural and recombinant PoIFN-gamma to induce the de novo expression of class II MHC antigens on porcine endothelial cells. To simplify the detection of biologically active porcine IFN-gamma, a sandwich ELISA was developed using the mAb P2G10 as a capture antibody and mAb P2C11 as the detecting reagent. The sensitivity of the assay for PolFN-gamma ranged from 1 to 50 ng/ml. Peripheral blood mononuclear cells (PBMC) from all pigs tested produced IFN-gamma when stimulated with either mitogen (PHA) or superantigen (SEB). In contrast, only PBMC obtained from pigs which had previously been vaccinated against PrV produced IFN-gamma in response to stimulation with this virus. Interestingly, cultures with the highest lymphoproliferative response did not necessarily have the highest level of IFN-gamma production.Furthermore, for recall viral antigen, the lymphoproliferative response decreased with time after immunization, whereas the IFN-gamma response increased. Thus, measurement of IFN-gamma production appears to be a good indicator of anti-viral immunological memory.
Animals↗
Pharmacokinetics and pharmacodynamics of single and multiple oral doses of a novel 5-lipoxygenase inhibitor (ABT-761) in healthy volunteers.
OBJECTIVE: This study evaluated the safety, pharmacokinetics and pharmacodynamics of ABT-761 [R(+)-N-[3-[5-(4-fluorophenylmethyl)-2-thienyl]-1- methyl-2-propynyl]-N-hydroxyurea], a new N-hydroxyurea analog. METHODS: This was a randomized, double-blind, placebo-controlled, single- and multiple-dose (15-day) study of ABT-761 (50 to 200 mg/day) in healthy, nonsmoking adult male volunteers. The pharmacokinetics were evaluated by investigation of the time- and dose-dependent effects of ABT-761, and the pharmacologic selectivity of ABT-761 was evaluated based on calcium ionophore-stimulated leukotriene B4 (LTB4) and thromboxane B2 (TXB2) biosynthesis ex vivo in whole blood. RESULTS: After single and multiple doses, mean observed time to reach maximum concentration values of ABT-761 ranged from 4.0 to 7.5 hours. Mean values for maximum concentration and area under the plasma concentration-time curve from 0 to 24 hours increased approximately linearly with dose. Mean terminal half-life and apparent volume of distribution during the terminal elimination phase of ABT-761 ranged from 15.4 to 17.8 hours and 69.5 to 78.9 L, respectively, and was dose independent. Steady state was reached on day 11 after multiple dosing. Less than 0.05% of unchanged ABT-761 was recovered in urine within the 24-hour period after day 15 dosing. Population ABT-761 plasma concentration at which 50% of the maximum possible inhibition was observed for LTB4 inhibition was 0.24 microgram/ml. No differences in mean TXB2 inhibition were observed between the subjects receiving ABT-761 and placebo. CONCLUSIONS: These results indicate that ABT-761 is a potent and selective inhibitor of 5-lipoxygenase and the pharmacokinetics of ABT-761 are time and dose independent between 50 and 200 mg/day after single and multiple dosing.
Administration, Oral↗
Impaired NK1.1+ T cells do not prevent the development of an IgE-dependent allergic phenotype.
BACKGROUND: The induction of TH2 immune responses is critically dependent on initial IL-4. Although crucial, the source of this early IL-4 has not been identified. One candidate is a CD1 restricted NK1.1+ T cell subpopulation which is known to produce such early IL-4. OBJECTIVES AND METHODS: The necessity of NK1.1+ T cells for the expression of an IgE-dependent phenotype was investigated in a NK1.1+ T cell deficient mouse model. The allergic phenotype was defined as immediate cutaneous hypersensitivity. It was induced by immunization of mice with ovalbumin. Mouse strains used were C57BL/6 mice and C57BL/6 mice homozygous for a targeted mutation of the beta2 microglobulin gene with consecutive loss of CD1 expression, which leads to a drastic reduction of NK1.1+ T cells. Manifestation of an allergic sensitization was assessed by intradermal allergen challenge after i.v. injection of Evans blue solution. The blue stained weal formations were quantified with the Bonitur method. In addition, the Th2 response was confirmed by the measurement of cytokines and serum immunoglobulins. The capability to produce early IL-4 was tested through the assessment of IL-4 mRNA shortly after a single challenge. RESULTS: Wild type and mutated mice did not differ in any of the immunological parameters measured. CONCLUSION: A single exposure to antigen with or without adjuvant induces early IL-4 production in C57BL/6 beta2m-/- mice. This early IL-4 is therefore independent of the presence of NK1.1+ T cells and functional MHC class I molecules and leads to IgE production and immediate cutaneous hypersensitivity.
Animals↗
Lack of cytochrome P450 1A2 interaction effect of ABT-761 on the pharmacokinetics of theophylline.
ABT-761 is a second-generation 5-lipoxygenase inhibitor for the treatment of asthma. The effects of ABT-761 on the pharmacokinetics of theophylline were assessed in 15 adult volunteers in a phase I, multiple-dose, open-label, one-period study. Subjects received a single 400-mg dose of theophylline on days 1 and 8 and 200-mg oral doses of ABT-761 once daily beginning on day 3 and continuing through day 9. The pharmacokinetic parameters of theophylline after administration of theophylline alone and concomitantly with ABT-761 were compared using a paired t-test. No statistically significant differences were observed between the pharmacokinetic parameters of theophylline administered alone and theophylline with concomitant administration of ABT-761. The 95% confidence interval for the ratio of the mean with ABT-761 dosing to the mean for theophylline alone was 0.970 to 1.127 for area under the plasma concentration-time curve and 0.887 to 1.036 for maximal plasma concentration. The lack of an inhibition effect by ABT-761 on theophylline clearance suggested that ABT-761 may have a low affinity for the cytochrome P450 1A2 isozyme, the primary isozyme responsible for theophylline metabolism.
Adult↗
Psychopathology in pediatric complex partial and primary generalized epilepsy.
Structured psychiatric interviews were administered to 60 children with complex partial seizure disorder (CPS), 40 children with primary generalized epilepsy with absences (PGE), and 48 control children, aged 5 to 16 years. Significantly more patients with epilepsy had psychiatric diagnoses compared with the control children. There were no statistically significant differences, however, in the number of patients with CPS and PGE with psychiatric diagnoses. Other than a schizophrenia-like psychosis found only in the patients with CPS, the two groups of patients had similar psychiatric diagnoses. The presence of psychopathology was related to significantly lower IQ scores and socioeconomic status, but not to seizure-related factors. These findings suggest that the psychopathology of children with CPS and PGE reflects different subtle neuropsychological deficits.
Adolescent↗
An audit of oestrogen implant hormone replacement therapy.
The aim of this review was to determine the factors that impact upon oestradiol levels in patients receiving oestradiol implants and to assess the relationship between symptom scores and oestradiol levels. In addition we sought to determine the incidence of tachyphylaxis (menopausal symptoms in spite of high oestradiol levels) among our patients, and to assess the degree of menstrual cycle control in the nonhysterectomized women receiving implant treatment. We undertook an audit of the medical records of 118 women who received 673 oestradiol implants (50 or 100 mg) over an 8-year period in the menopause clinics at Royal North Shore Hospital. Data on patient age, clinical diagnosis, symptom score, previous or subsequent hysterectomy, oestradiol implant dosage (50 mg or 100 mg), number of doses, oestradiol levels and concurrent testosterone implant insertion were recorded. We found that implant dosage (p<0.001) and implant number (p<0.001) were the factors that significantly impact upon oestradiol levels. Concomitant testosterone implant usage (p=0.74), patient age (p=0.14) and hysterectomy (p=0.57) did not have a statistically significant effect upon oestradiol levels. The incidence of tachyphylaxis was 1.7% (2 patients). There was no relationship between oestradiol levels and symptom scores (p=0.69). Oestradiol implant treatment, when administered on the basis of return of symptoms, without a strict target oestradiol level, results in a steady increase in baseline oestradiol levels. The dosage used and the number of implants received are important factors influencing oestradiol levels. The incidence of tachyphylaxis is low when patients are counselled regarding the lack of agreement between symptom scores and oestradiol levels.
Adult↗
Deficiency of the growth hormone-insulin-like growth factor-I axis potentially involved in age-related alterations in body composition.
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Aging↗
Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer.
PURPOSE: The administration of fluorouracil (5-FU) by continuous intravenous infusion (CI) is an alternative to the bolus administration of 5-FU in patients with advanced colorectal cancer. Although more than 1,200 patients have been enrolled onto randomized trials that compared these two treatment modalities, there is still no definitive evidence of an advantage of 5-FU CI, and the magnitude of this advantage, if any, is also controversial. A meta-analysis was performed to assess this benefit in terms of tumor response and survival, and to compare the toxicity profiles of these two modalities of administration of 5-FU. DESIGN: Individual data of 1,219 patients included in six randomized trials served as the basis for this meta-analysis, which was conducted by an independent secretariat in close collaboration with the investigators. RESULTS: Tumor response rate was significantly higher in patients assigned to 5-FU CI than in patients assigned to 5-FU bolus (22% v 14%; overall response odds ratio, 0.55; 95% confidence interval [95% CI], 0.41 to 0.75; P = .0002). Overall survival was also significantly higher in patients assigned to 5-FU CI (overall hazards ratio [HR], 0.88; 95% CI, 0.78 to 0.99; P = .04), although the median survival times were close. Multivariate analyses showed that randomized treatment and performance status were the only two significant predictors of tumor response, whereas the same plus primary tumor site were independent significant predictors of survival (patients with rectal cancer did somewhat better). Grade 3 or 4 hematologic toxicity was more frequent in patients assigned to 5-FU bolus (31% v 4%; P < 10(-16)), whereas hand-foot syndrome was more frequent in the 5-FU CI group (34% v 13%; P < 10(-7)). CONCLUSION: 5-FU CI is superior to 5-FU bolus in terms of tumor response and achieves a slight increase of overall survival. The hematologic toxicity is much less important in patients who receive 5-FU CI, but hand-foot syndrome is frequent in this group of patients.
Antimetabolites, Antineoplastic↗
Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors.
PURPOSE: Fluorouracil (5-FU) continuous infusion is superior to 5-FU bolus in patients with advanced colorectal cancer, but the survival difference between the two treatments is small and, therefore, the difference in toxicity profile is crucial in choosing a treatment for individual patients. MATERIALS AND METHODS: We conducted a meta-analysis of all randomized trials that compared 5-FU bolus with 5-FU CI, based on individual data from 1,219 patients, to compare the toxicity of the two schedules of 5-FU administration and to identify predictive factors for toxicity. The toxicities considered were World Health Organization (WHO) grade 3 to 4 anemia, thrombopenia, leukopenia, neutropenia, nausea/vomiting, diarrhea, mucositis, and hand-foot syndrome. RESULTS: Hematologic toxicity, mainly neutropenia, was more frequent with 5-FU bolus than with 5-FU CI (31% and 4%, respectively; P < .0001). Hand-foot syndrome was less frequent with 5-FU bolus than with 5-FU CI (13% and 34%, respectively; P < .0001). There was no difference between the two treatment groups in terms of other nonhematologic toxicities. Independent prognostic factors were age, sex, and performance status for nonhematologic toxicities, performance status, and treatment for hematologic toxicities, and age, sex, and treatment for hand-foot syndrome. CONCLUSION: Based on a large data set, this study confirmed and quantified the toxicity profile of the two schedules of administration of 5-FU and allowed the identification of clinical predictors of toxicity.
Colorectal Neoplasms↗
Internal calibration for a total body counter.
Whole body counting is used to monitor the ingestion of radioactivity by radiation workers when unsealed sources are used in biomedical or industrial applications. The whole body counter at Lucas Heights Research Laboratories has been running for four decades, and radiation workers are frequently monitored for radioactive contamination. In a retrospective study of total body potassium (TBK) values in radiation workers, it was found that the results varied markedly with time. In that TBK is a slowly varying quantity in healthy individuals, variation in TBK is therefore indicative of instability in the counting system. We conclude that TBK can be used as an internal calibration for the whole body counter. The activity of radioisotope contaminants can therefore be expressed relative to the value of the potassium activity in a given subject.
Humans↗
Principal findings from the Washington State cognitive services demonstration project.
In addition to dispensing, pharmacists are ideally positioned to provide cognitive services that are targeted at optimizing drug therapy through identification and resolution of drug therapy problems. The Washington Cognitive Activities and Reimbursement Effectiveness project sought to determine: (1) if pharmacists would respond to a financial incentive by performing more cognitive services, and (2) the effect on drug cost of cognitive services they performed.
Attitude of Health Personnel↗