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Biomedical subjects

R Hansen

Publications and source records attributed to R Hansen.

At least 73 records · Page 4Linked to original sources
PubMed1995

Somatostatin prevents the postoperative increases in plasma amino acid clearance and urea synthesis after elective cholecystectomy.

The importance of glucagon on postoperative changes in hepatic amino-nitrogen conversion were investigated in six patients undergoing elective cholecystectomy for uncomplicated gall stones. Patients were given infusions of somatostatin (bolus of 6 micrograms/kg followed by continuous infusion of 6 micrograms/kg/h) from induction of anaesthesia to the end of investigation, the first postoperative day (30 hours). Controls were 16 patients undergoing the same procedures omitting the somatostatin infusion. In all patients blood concentration and plasma clearance of total alpha-amino-nitrogen, and amino acid stimulated rate of urea synthesis were measured. Elective cholecystectomy decreased blood alpha-amino-nitrogen concentration from mean (SEM) 2.9 (0.2) to 2.4 (0.1) mmol/l (p < 0.05), increased the clearance of total alpha-amino-nitrogen from 5.2 (0.3) to 6.6 (0.3) ml/s (p < 0.05), and increased the rate of amino acid stimulated urea synthesis from 27 (1) to 37 (2) mumol/s (p < 0.05) pointing to increased hepatic removal of amino-nitrogen at expense of plasma amino-nitrogen. Infusion of somatostatin prevented increase of glucagon for 24 hours after surgery, and prevented the negative changes in postoperative nitrogen homeostasis resulting from the postoperative changes in hepatic nitrogen conversion, suggesting glucagon as mediator. The exact mechanism remains in doubt, however, because of the multiple effects of somatostatin.

Adult↗
PubMed1994

Stereoselective metabolism of the 5-lipoxygenase inhibitor A-78773.

Based on the knowledge that glucuronidation was a major route of metabolism of the N-hydroxyurea class of 5-lipoxygenase inhibitors, a simple in vitro glucuronidation assay was established using liver microsomes from various species, including man. Compounds that were potent inhibitors of 5-LO and showed a reduced metabolic liability in vitro were then characterized more extensively in experimental animals. This prudent usage of in vitro glucuronidation proved to be highly efficient and was indispensable in the identification of A-78773, a potent new long-acting 5-LO inhibitor. Further studies with liver microsomes revealed that glucuronidation of A-78773 was stereoselective and that the R(+) enantiomer was considerably more resistant to conjugation than the S(-) stereoisomer. Pharmacokinetic studies in experimental animals and humans confirmed the greater metabolic stability of the R(+) enantiomer. A single 400-mg oral dose of A-78773 inhibited ex vivo leukotriene biosynthesis for more than 24 hours. Since 78% of the drug plasma AUC following A-78773 administration was accounted for by the R(+) enantiomer, it is reasonable to assume that the majority of the leukotriene inhibition caused by the racemate is attributable to the R(+) enantiomer, A-79175, particularly at the later times. The equivalent 5-lipoxygenase inhibitory potency coupled with the superior pharmacokinetic profile of the R(+) enantiomer, A79175, compared to the S(-) enantiomer, A-79176, indicate that the development of this compound may be preferable to the racemate A-78773.

Animals↗
PubMed1994

Socioeconomic studies of high-level nuclear waste disposal.

The socioeconomic investigations of possible impacts of the proposed repository for high-level nuclear waste at Yucca Mountain, Nevada, have been unprecedented in several respects. They bear on the public decision that sooner or later will be made as to where and how to dispose permanently of the waste presently at military weapons installations and that continues to accumulate at nuclear power stations. No final decision has yet been made. There is no clear precedent from other countries. The organization of state and federal studies is unique. The state studies involve more disciplines than any previous efforts. They have been carried out in parallel to federal studies and have pioneered in defining some problems and appropriate research methods. A recent annotated bibliography provides interested scientists with a compact guide to the 178 published reports, as well as to relevant journal articles and related documents.

Government Agencies↗
PubMed1993

Preclinical and clinical activity of zileuton and A-78773.

The importance of leukotrienes as mediators of inflammation and bronchoconstriction was examined with two recently described 5-lipoxygenase inhibitors, zileuton and A-78773. Preclinical evaluation of these two molecules indicates that they are potent, selective, direct, reversible inhibitors of 5-lipoxygenase with activity in a variety of purified cells and in more complex biological systems such as whole blood, lung fragments, and tracheal tissues. In various animals models of inflammation and allergy, the molecules inhibited edema, inflammatory cell influx, and bronchospasm. These observations are consistent with the recent clinical success of zileuton in treating asthma and inflammatory bowel disease. In all preclinical systems tested thus far, A-78773 is more potent and longer acting than zileuton, indicating that the molecule could be even more effective in the clinic than zileuton and that both molecules are useful tools in defining the role of leukotrienes in preclinical and clinical settings.

Animals↗
PubMed1993

Late follow-up of dual-chamber rate-adaptive pacing.

Dual-chamber pacing systems with sensor-based rate-adaptive capability (DDDR pacemakers) provide paced patients with the potential benefits of both a reliable chronotropic response and maintenance of atrioventricular (AV) synchrony. However, there is concern that clinical and programming complexities may necessitate frequent reprogramming of pacemakers from the DDDR mode to less physiologic pacing modes (in particular VVI or VVIR). Consequently, this study assessed the stability of pacing-mode programming, and the factors affecting pacing-mode selection in patients with a DDDR-capable pacing system. Clinical status during follow-up (18.2 +/- 6.7 months) was assessed in 75 patients. Principal diagnoses providing an indication for pacing were: (1) AV block alone, 18 of 75 patients (24%); (2) sick sinus syndrome alone, 41 (55%); and (3) combined AV block and sick sinus syndrome, 16 (21%). Twenty-three patients had history of atrial tachyarrhythmias. At implantation, 66 devices (88%) were programmed to DDDR mode, 7 (9%) to DDD, and 2 (3%) to DVIR. At last follow-up, the respective distribution of programmed modes was 83% DDDR, 10% DDD, 4% DVIR and 3% VVIR. During the study, the initial pacing mode remained unchanged in 54 patients (72%) and needed modification in 21 (28%). Of the latter 21 patients, atrial tachycardia was the basis for a programming change in 11 (52%), of whom 8 had history of atrial tachycardias. In general, postimplant atrial arrhythmia occurrences proved controllable, and ultimately return to a rate-adaptive dual-chamber pacing mode (DDDR, DDD or DVIR) was achieved in most cases. The remaining reprogrammings were primarily to optimize hemodynamic benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Ciprofloxacin-induced granulomatous interstitial nephritis and localized elastolysis.

Ciprofloxacin is known to cause acute interstitial nephritis. We report the first case of ciprofloxacin-induced granulomatous interstitial nephritis and localized elastolysis. The patient presented with acute renal failure and skin lesions following a 14-day course of ciprofloxacin administered for cellulitis. The patient had symmetric, palm-sized, tender violaceous plaques on both axillae. The renal biopsy revealed granulomatous interstitial disease. A skin biopsy revealed an elastolytic process with histocytic infiltration and calcification. After discontinuing ciprofloxacin and starting a short course of steroid therapy, the skin lesion and renal function improved promptly. The nephritis relapsed after prednisone was discontinued and responded to a second course of steroid therapy. Ciprofloxacin, like penicillin, can cause granulomatous interstitial nephritis and elastolysis. A prolonged course of steroid therapy may be indicated in patients with ciprofloxacin-induced granulomatous interstitial nephritis to avoid early relapse.

Ciprofloxacin↗
PubMed1993

Van Beaumont's formula is valid during haemodialysis. Spectrophotometric determination of body circulating haemoglobin.

Van Beaumont's formula is a convenient method to calculate changes in plasma volume from changes in haematocrit. The calculation is based on the assumption of a constant body red-cell volume. In order to evaluate the validity of this assumption during isovolaemic haemodialysis, we measured body circulating haemoglobin, blood volume and plasma volume by carbon monoxide dilution. No change in body circulating haemoglobin or plasma volume occurred by either method. Therefore, we conclude that van Beaumont's formula is valid during isovolaemic haemodialysis.

Adult↗
PubMed1992

Characterization of the Antirrhinum floral homeotic MADS-box gene deficiens: evidence for DNA binding and autoregulation of its persistent expression throughout flower development.

We have determined the structure of the floral homeotic deficiens (defA) gene whose mutants display sepaloid petals and carpelloid stamens, and have analysed its spatial and temporal expression pattern. In addition, several mutant alleles (morphoalleles) were studied. The results of these analyses define three functional domains of the DEF A protein and identify in the deficiens promoter a possible cis-acting binding site for a transcription factor which specifically upregulates expression of deficiens in petals and stamens. In vitro DNA binding studies show that DEF A binds to specific DNA motifs as a heterodimer, together with the protein product of the floral homeotic globosa gene, thus demonstrating that the protein encoded by deficiens is a DNA binding protein. Furthermore, Northern analysis of a temperature sensitive allele at permissive and non-permissive temperatures provides evidence for autoregulation of the persistent expression of deficiens throughout flower development. A possible mechanism of autoregulation is discussed.

Alleles↗
PubMed1992

Anaplasmosis in Uganda. I. Use of dried blood on filter papers and serum samples for serodiagnosis of anaplasmosis--a comparative study.

The suitability of blood collected on filter papers in comparison with corresponding conventional serum samples in the diagnosis of bovine anaplasmosis was studied using the complement fixation test, DOT-ELISA, Western immunoblot and rapid card agglutination test. Dried blood on Whatman filter paper no. 1 was eluted in PBS 0.05% Tween 20 giving an initial dilution of 1:10. The reactivity of the eluted samples in both DOT-ELISA and Western immunoblotting were similar to those obtained with the corresponding straight serum sample dilutions. Filter paper samples gave lower reactivity in the remaining tests when compared with corresponding serum samples. There was no significant difference in the reactivity between the eluates from filter papers stored at temperatures ranging between 15.5 and 24 degrees C and those kept refrigerated. Storage at 15.5 to 24 degrees C did not significantly affect reactivity for up to six months. Eluates from filter papers stored for six months at 15.5 to 24 degrees C continued to give similar reactivity as those from freshly prepared filter papers in both DOT-ELISA and Western blot, and in the rapid card agglutination test. It is concluded that collecting blood on filter papers is a suitable technique for large scale seroepidemiological studies on anaplasmosis and offers many advantages in developing countries where transport and cold chain facilities are a major constraint.

Agglutination Tests↗
PubMed1992

Antioxidant depletion in aortic crossclamping ischemia: increase of the plasma alpha-tocopheryl quinone/alpha-tocopherol ratio.

To assess whether oxidative stress contributes to the ischemia/reperfusion injury of aortic surgery, the contents of alpha-tocopherol, alpha-tocopheryl quinone, ascorbate, lipid-derived malondialdehyde, protein thiols, cholesterol, and lactate were analyzed in plasma samples from 24 patients subjected to aortic crossclamping. alpha-Tocopherol, ascorbate, and protein thiols decreased during ischemia, whereas alpha-tocopheryl quinone increased in all but two cases, doubling on average in proportion to alpha-tocopherol. Upon reperfusion alpha-tocopherol, ascorbate, and protein thiols remained low, whereas alpha-tocopheryl quinone returned to the preischemic level. Lipid-derived malondialdehyde (a measure of lipid hydroperoxides) increased significantly only during reperfusion. The results suggest that oxidative stress occurs simultaneously with ischemia/reperfusion during aortic surgery, and that measurement of the tocopheryl quinone/tocopherol ratio may shed new light on the underlying pathological events.

Aged↗
PubMed1992

Anaplasmosis in Uganda. I. Use of dried blood on filter paper and serum samples for serodiagnosis of anaplasmosis--a comparative study.

The suitability of blood collected on filter papers in comparison with corresponding conventional serum samples in the diagnosis of bovine anaplasmosis was studied using the Complement Fixation Test (CFT), DOT-ELISA, Western immunoblot and Rapid Card Agglutination Test (RCAT). Dried blood on Whatman filter paper no. 1 was eluted in 1.8 ml of PBS 0.05% Tween 20 given an initial dilution of 1:100. The reactivity in both DOT-ELISA and Western immunoblotting was similar to that obtained with the sera diluted 1:100. Filter paper samples gave lower reactivity in all the tests as compared with corresponding serum samples. There was no significant difference in the reactivity between the eluates from filter papers stored at room temperature and those stored at 4 degrees C. Storage at room temperature did not significantly affect reactivity for up to 6 months. Eluates from filter papers stored for 6 months at room temperature continued to give similar reactivity to those from freshly prepared filter papers in both DOT-ELISA and Western blot, and in the Rapid Card Agglutination Test. It is concluded that collecting blood on filter papers is a suitable technique for large-scale screening and for seroepidemiological studies on anaplasmosis, and offers many advantages especially in developing countries where transport and cold chain facilities are a major constraint.

Anaplasmosis↗
PubMed1992

Immunogenicity and protective efficacy of solubilized merozoite-enriched Theileria sergenti immunogens. I: Protection against homologous stabilate challenge.

Theileria sergenti were isolated from infected erythrocytes by hypotonic lysis, and soluble merozoite antigens were purified by sonication and differential centrifugation. The preparation contained 29, 34, 35 and 105 kD immuno-dominant poly-peptides. The soluble antigens (0.5 mg/ml) were prepared and fortified with Freund's adjuvant. Five month old naive Korean calves were subcutaneously inoculated with the preparation and a booster dose was administered 4 weeks later. Nine weeks after the booster dose, vaccinates and controls were challenged with a homologous stabilate (5.6 x 10(6) RBC/dose, 40% Parasitemia). All animals were monitored for hematocrit, total erythrocyte count, parasitemia and for the specific antibody by Western immunoblot (WB) and indirect immuno-fluorescent antibody (IFA) test. By 18 weeks after vaccination (6 weeks after the challenge), vaccinated cattle had an average IFA titer of 1:10,240 compared with 1:1,280 of the controls. The vaccinates showed negligible change in hematocrit and total RBC count whereas control animals showed significant (p less than 0.05) hematological changes and associated anemia. After vaccination and challenge, the antibody responses demonstrated that vaccination had induced significant production of antibody to the 29 and 35 kD polypeptides. The latter polypeptide was much more strongly recognized by the vaccinated animals, and thus it may be a potential candidate for the vaccine.

Animals↗
PubMed1992

Immunogenicity and protective efficacy of solubilized merozoite-enriched Theileria sergenti immunogens. II: Protection against natural exposure under field conditions.

A Theileria sergenti soluble merozoite preparation containing the 29, 34, 35 and 105 KD as the immunodominant polypeptides, was evaluated for efficacy, safety and protectivity in Holstein calves against virulent field tick challenge. The soluble antigens (100 mg/dose) were fortified with either complete or incomplete Freund's adjuvant. Twenty naive calves, aged one month, were subcutaneously inoculated with the preparation and a booster dose was administered 4 weeks later. Twenty additional calves served as controls. Five weeks after the booster dose, vaccinates and uninoculated controls were moved to a pasture, a heavily tick infested area in Cheju-do, Korea. The vaccinates showed negligible change in hematocrit and total RBC count whereas control animals showed significant (p < 0.05) hematological changes and associated anemia. Only 30% of vaccinates required chemotherapy after the experiment was terminated. All control animals required chemotherapy and 25% received blood transfusion. The highest percent parasitized erythrocytes in vaccinated cattle was 0.4% as compared with 3.6% among controls during the month of July. A significant difference (p < 0.05) was observed in the rate of body weight increase. Significant differences were also noted in serum albumin, aspartate aminotransferase, total protein and bilirubin. Significantly more vaccinated cattle maintained normal ranges of hematological and biochemical values as compared with the control group. It is suggested that soluble merozoite T. sergenti antigens may be potential vaccine candidates for developing a genetic vaccine in Korea.

Animals↗
PubMed1992

Anaplasmosis in Uganda. III. Parasitological and serological evidence of Anaplasma infection in Ugandan goats.

Randomly selected goat sera from north-western, central, and south-western regions of Uganda were analyzed parasitologically and serologically for evidence of anaplasmosis. Prevalence rates of 3.2% by parasitemia, 4.8% by card-agglutination test, and 12.9% by DOT-ELISA combined with western blotting were established. Parasitologically positive samples were consistently serologically positive. Positive samples were all from either the north-western or south-western regions of the country. Goats in these regions graze with cattle and are presumable exposed to the same tick species. There was no evidence of clinical caprine anaplasmosis, whereas bovine anaplasmosis cases are very common. Rhipicephalus evertsi was frequently observed on goats which cograze with cattle.

Anaplasma↗
PubMed1991

Continuous systemic 5-fluorouracil infusion in refractory prostatic cancer.

Twenty patients with metastatic prostatic cancer were treated on an ambulatory basis with continuous 5-fluorouracil (5-FU) infusion 250-300 mg/M2 per day through a chronic indwelling central venous catheter. All patients had symptomatic, progressive disease despite previous standard therapies. Partial remission was seen in 2 of 20 patients (10%), stable disease in 9 of 20 (45%), and progressive disease in 9 of 20 (45%); mean duration of benefit in responding and stable disease patients was six months. Improvement in pain and ECOG performance status were seen in most of the patients in the responding and stable disease categories. Forty percent of the patients experienced no significant drug toxicity; treatment interruption was necessary for stomatitis in 6 patients (30%), hand/foot syndrome in 3 patients (15%), and diarrhea in 1 patient (5%). No significant myelosuppression or other significant organ toxicities were encountered. Continuous systemic venous infusion of 5-FU may provide significant palliative effect for some patients with symptomatic, refractory carcinoma of the prostate.

Drug Evaluation↗
PubMed1991

[Simpson's atherectomy in embolizing leg artery stenoses].

We report on the treatment and follow-up of six patients with an unilateral "blue toe" syndrome. This is caused by atheromatous micro-embolisation to the digital arteries and requires urgent attention due to the painful cutaneous necroses and impending digital gangrene. In all patients, Simpson's atherectomy of proximally situated femoropopliteal stenoses caused the pre-gangrenous digital changes to heal completely. In a mean observation period of ten months no relapse occurred. The embolising material was presumably parietal fibrino-platelet thrombi which could be observed with angioscopy and were regularly detectable histologically in the excised tissue.

Aged↗