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Biomedical subjects

B Nielsen

Publications and source records attributed to B Nielsen.

At least 73 records · Page 4Linked to original sources

Heat acclimation--mechanisms of adaptation to exercise in the heat.

Repeated exposures to exercise and heat produce acclimatization, changes in physiological function by which the tolerance to heat stress is improved. The main issues to be discussed are the possible mechanisms for the increase in plasma volume, the increase in sweating rate and the endocrine responses to exercise with acclimation to both dry and humid heat. This will be discussed on the basis of the literature and our recent and ongoing experiments. We have tried to analyze this by comparing different acclimation procedures: exercise at 50-60% V/O2max, 60-90 min, dry heat 40 degrees C, 20% RH; 40-50% VO2max, 45-51 min, humid heat 35 degrees C, 85% RH; and 70-75% VO2max, 30-35 min, dry heat 40 degrees C, 20% RH. Subjects exercised in dry or humid heat for 8-12 consecutive days. Acclimation was achieved by all procedures, as indicated by a lower heart rate, increased plasma volume and sweating rate. We hypothesize that it is the repeated exposures to high core temperature that induce the changes, possibly via endocrine factors activated by the rising core temperature and the prolonged exercise. The increased sensitivity of the sweat glands for thermal and hormonal stimuli after acclimation may be obtained through an increase in receptor density for neural and humoral stimuli, an increase in the size, or, in number of active sweat glands.

Acclimatization↗

Film processing and the environment. Reducing pollution, water consumption, and costs.

PURPOSE: X-ray film processing is associated with pollution from photo chemicals and from the water used to rinse the film. We tested a new processing system that was aimed at reducing both environmental pollution and costs through the use of solid photo chemicals and recirculation of the rinsing water. MATERIAL AND METHODS: Before and after the installation of new mixers for the solid chemicals and a system for recirculating the rinsing water, we measured: water consumption, processor function quality, image quality, archivability, and the waste-silver content in the rinsing water. RESULTS: After the installation of a simple system for recirculating the rinsing water, there was an 88% reduction in water and film consumption as shown in the amount of water/m2 film that was used. At the same time, the release of silver-contaminated rinsing water directly into the sewers was stopped. Image quality remained unchanged. Archivability was assessed at more than 100 years. The solid photo chemicals and specially designed mixers proved efficient and provided a stable image quality of high standard. It was thus possible to reduce the risk of pollution from the transportation, storage and handling of liquid chemicals. CONCLUSION: A simple recirculation system for the rinsing water would significantly reduce water consumption and eliminate contamination of the environment by silver. The on-site preparation of photo chemicals proved viable and reduced the costs of film processing.

Environmental Pollution↗

Combination of enalapril and low-dose thiazide reduces normoalbuminuria in essential hypertension.

OBJECTIVE: To examine the effect of the combination of enalapril with a very low dose of hydrochlorothiazide versus atenolol on urinary albumin excretion in normoalbuminuric patients with mild to moderate essential hypertension. A secondary objective was to compare the effects of the two regimens in patients with different levels of albuminuria. DESIGN: A 12 weeks, randomized, double-blind, double-dummy, multicenter, comparative study with two parallel groups. SETTING: General practices in Denmark and Finland. PATIENTS: The subjects comprised 174 patients with mild to moderate essential hypertension, normal serum creatinine and no proteinuria. INTERVENTIONS: Enalapril/hydrochlorothiazide (20/6 mg) daily or atenolol (50 mg) daily. MAIN OUTCOME MEASURES: Urinary albumin: creatinine ratio and blood pressure. RESULTS: At baseline, normoalbuminuria was found in 74 and 85 patients in the enalapril/hydrochlorothiazide and atenolol groups, respectively. Blood pressure was reduced similarly by both treatments. The ratio of urinary albumin to creatinine in normoalbuminuric patients was significantly reduced during treatment with enalapril/hydrochlorothiazide at 20/6 mg (from geometic mean x/divided by antilog SD of 0.53 x/divided by 1.77 to 0.47 x/divided by 1.58 mg/mmol, P=0.02) but was unchanged during atenolol treatment (0.55 x/divided by 1.74 and 0.58 x/divided by 1.87 mg/mmol). The difference between the two treatments was statistically significant (P=0.03) and was predominantly achieved through a reduction of albuminuria in the upper-normal range during enalapril/hydrochlorothiazide treatment. CONCLUSIONS: Therapy with enalapril/hydrochlorothiazide at 20/6 mg and atenolol at 50 mg once daily reduced blood pressure similarly in patients with essential hypertension. Suppression of urinary albumin excretion within the normoalbuminuric range was observed during treatment with enalapril/hydrochlorothiazide at 20/6 mg.

Albuminuria↗

Patient-treatment matching improves compliance of alcoholics in outpatient treatment.

In chronic medical disorders, patient compliance is very poor and often less than 50%. The purpose of this investigation was to determine whether the proper matching of patient, treatment, and therapist would improve patient compliance in the outpatient treatment of alcoholics. We randomly placed 119 alcoholics who had commenced protracted outpatient treatment for alcoholism in either low or high structured treatments. These 119 patients were offered 12 months of individual treatment. Interruption of this treatment was recorded as noncompliance. The treatment courses were expressed in survival curves. The consequence of compliance for long-term prognosis was described by means of the Addiction Severity Index. The form of treatment in itself had no importance for compliance. However, correct matching of a patient and a treatment structure resulted in a compliance rate of 63% as opposed to 38% compliance among mismatched patients. Twenty-four months after the initiation of treatment, patients in the compliance group had a significantly higher level of function than those in the noncompliance group. Our investigation of alcoholics involved in outpatient treatment shows that the correct matching of patients and treatment structure improves compliance and long-term prognosis. It is hoped that the present investigation will generate interest in future research on correct matching to gain improved compliance in patients with a chronic medical disorder.

Adaptation, Psychological↗

Modulatory function on autologous myeloid progenitor cells of clonal T-lymphocytes following autologous bone marrow transplantation.

We have studied the regulatory capacity of clonal T-lymphocytes from patients undergoing autologous bone marrow transplantation (ABMT) on the generation of CFU-GM from their harvest marrow preparations. To this end, T-lymphocytes from peripheral blood from 5 patients undergoing ABMT isolated 10 d before and 7, 14 and 28 d post-ABMT were placed in limiting dilution conditions (384 wells for each patient at each time point) and polyclonally stimulated. From more than 1600 wells with growth from the 5 patients, preparations from more than 900 wells could be expanded (range between patients 33-452) and identified by immunophenotyping (IP) and flow cytometry (FCM) by their exclusive expression of CD4 or CD8. This was significantly fewer than seen in normal donors, especially so at d 7 and 14 post-ABMT The ratio between CD4+ and CD8+ clones varied between 0.6 and 2.8 (median 1.3) and was significantly lower in the patients compared to normal donors (median 3.1; range 3.0-6.5). When the clonal T-cell preparations were co-cultured with autologous bone marrow cells obtained at the time of harvest and depleted for T-lymphocytes, the vast majority of both CD4+ and CD8+ clones exerted a clear enhancement on the CFU-GM growth with no relation to time of blood sampling in its the magnitude. Moreover, a trend seen in the normal donors towards CD4+ clones being more effective in this enhancement was not observed in ABMT patients. We conclude that clonal T-cells from ABMT patients, irrespective of their phenotype and time of isolation, exert an enhancement on the growth of autologous CFU-GM, which is equal to that seen in normal donors.

Adult↗

Use of muscle fluid as a source of antibodies for serologic detection of Salmonella infection in slaughter pig herds.

Fluid drained from a muscle tissue sample was used as an alternative to serum for the detection of specific anti-Salmonella antibodies in an indirect LPS enzyme-linked immunosorbent assay (ELISA). In the first study, serum and muscle fluid from 3 pigs experimentally infected with Salmonella typhimurium showed parallel dilution-response relationships when ELISA optical density (OD) values were plotted against sample dilution. ELISA results obtained with serum diluted 1:400 corresponded to those from muscle fluid diluted 1:30. In a second study, using the predetermined dilutions of individually paired serum and muscle fluid samples from 103 pigs, a high degree of concordance between the serum ELISA and the muscle fluid ELISA was observed. Limits of agreement between the 2 methods were calculated as -8.9 to 12.3 OD%, which was considered acceptable. The muscle fluid ELISA had specificities of 0.91-1.0 and sensitivities of 0.80-0.89 at various cutoff values as compared with the serum ELISA. Muscle fluid is a useful postmortem alternative to serum when used with an ELISA to detect anti-Salmonella antibodies.

Abattoirs↗

(S)-homo-AMPA, a specific agonist at the mGlu6 subtype of metabotropic glutamic acid receptors.

Our previous publication (J. Med. Chem. 1996, 39, 3188-3194) described (RS)-2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid (Homo-AMPA) as a highly selective agonist at the mGlu6 subtype of metabotropic excitatory amino acid (EAA) receptors. Homo-AMPA has already become a standard agonist for the pharmacological characterization of mGlu6 (Trends Pharmacol. Sci. Suppl. 1997, 37-39), and we here report the resolution, configurational assignment, and pharmacology of (S)- (6) and (R)- (7) Homo-AMPA. Using the "Ugi four-component condensation", 3-(3-ethoxy-5-methylisoxazol-4-yl)propanal (10) was converted into the separable diastereomeric derivatives of 6 and 7, compounds 12 and 11, respectively. Deprotection of 12, in one or two steps, gave extensively racemized 6, which was converted in low yield into 6 (99.0% ee) through several crystallizations. 6 (99.7% ee) and 7 (99.9% ee) were finally obtained by preparative chiral HPLC. The configurational assignments of 6 and 7 were based on 1H NMR spectroscopic studies on 12 and 11, respectively, and circular dichroism studies on 6 and 7. Values of optical rotations using different solvents and the chiral HPLC elution order of 6 and 7 supported the results of the spectroscopic configurational assignments. The activities of 6 and 7 at ionotropic EAA (iGlu) receptors and at mGlu1-7 were studied. (S)-Homo-AMPA (6) was shown to be a specific agonist at mGlu6 (EC50 = 58 +/- 11 microM) comparable in potency with the endogenous mGlu agonist (S)-glutamic acid (EC50 = 20 +/- 3 microM). Although Homo-AMPA did not show significant effects at iGlu receptors, (R)-Homo-AMPA (7), which was inactive at mGlu1-7, turned out to be a weak N-methyl-D-aspartic acid (NMDA) receptor antagonist (IC50 = 131 +/- 18 microM).

Animals↗

Molecular pharmacology of 4-substituted glutamic acid analogues at ionotropic and metabotropic excitatory amino acid receptors.

The pharmacology of (2S,4R)-4-methylglutamic acid, (2S,4S)-4-methylglutamic acid and (S)- and (R)-4-methyleneglutamic acids (obtained in high chemical and enantiomeric purity from racemic 4-methyleneglutamic acid by chiral HPLC using a Crownpak CR(+) column), was examined in binding experiments using rat brain ionotropic glutamate receptors, and in functional assays using cloned metabotropic glutamate (mGlu) receptors. As a notable result of these studies, (2S,4R)-4-methylglutamic acid and (2S,4S)-4-methylglutamic acid were shown to be selective for kainic acid receptors and mGlu receptors (subtypes 1alpha and 2), respectively, whereas (S)-4-methyleneglutamic acid showed high but rather non-selective affinity for the (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA), kainic acid, NMDA and mGlu receptors (subtypes 1alpha and 2). Although none of the compounds were specific for any of the receptor subtypes, the results demonstrate that each of these structurally related compounds has a distinct pharmacological profile.

Animals↗

Elimination of Salmonella typhimurium infection by the strategic movement of pigs.

Three field investigations were carried out to assess the feasibility of raising salmonella-free finishers from pigs born in infected herds, by moving the pigs to clean and disinfected facilities before their expected exposure to the bacteria from the environment. Three herds with persistently high levels of subclinical infection with S typhimurium in the finishing pigs were used. They practised all-in all-out management in the nurseries and in the grower units. A total of 844 pigs were moved, either at weaning, from the nursery, or from the grower unit to newly built or rigorously cleaned and disinfected finishing units with no known history of salmonella infection. No detectable infection was observed at slaughter either serologically or bacteriologically by random testing of the pigs which had been moved, whereas a proportion of the pigs raised at the same time in the continuous systems on the farms were found to be infected.

Animal Husbandry↗

Acute and adaptive responses in humans to exercise in a warm, humid environment.

Acute and repeated exposure for 8-13 consecutive days to exercise in humid heat was studied. Twelve fit subjects exercised at 150 W [45% of maximum O2 uptake (V.O2,max)] in ambient conditions of 35 degrees C and 87% relative humidity which resulted in exhaustion after 45 min. Average core temperature reached 39.9 +/- 0.1 degrees C, mean skin temperature (T-sk) was 37.9 +/- 0.1 degrees C and heart rate (HR) 152 +/- 6 beats min-1 at this stage. No effect of the increasing core temperature was seen on cardiac output and leg blood flow (LBF) during acute heat stress. LBF was 5.2 +/- 0.3 l min-1 at 10 min and 5.3 +/- 0.4 l min-1 at exhaustion (n = 6). After acclimation the subjects reached exhaustion after 52 min with a core temperature of 39.9 +/- 0.1 degrees C, T-sk 37.7 +/- 0.2 degrees C, HR 146 +/- 4 beats min-1. Acclimation induced physiological adaptations, as shown by an increased resting plasma volume (3918 +/- 168 to 4256 +/- 270 ml), the lower exercise heart rate at exhaustion, a 26% increase in sweating rate, lower sweat sodium concentration and a 6% reduction in exercise V.O2. Neither in acute exposure nor after acclimation did the rise of core temperature to near 40 degrees C affect metabolism and substrate utilization. The physiological adaptations were similar to those induced by dry heat acclimation. However, in humid heat the effect of acclimation on performance was small due to physical limitations for evaporative heat loss.

Adaptation, Physiological↗

Quality of life and patient preference for sequential versus continuous combined HRT: the UK Kliofem multicenter study experience. UK Continuous Combined HRT Study Investigators.

Hormone replacement therapy (HRT) must be taken for many years to attain the long-term benefits on osteoporosis and cardiovascular disease. However, this level of compliance with HRT is rarely achieved. This analysis documents the effect of continuous combined HRT with Kliogest on the relief of menopausal symptoms, and the patient preference for HRT over a 9-month treatment period. A total of 2151 postmenopausal women, of whom 1435 were currently on sequential therapy and 716 had not been previously treated, were enrolled from 55 centers in the UK. Women received a daily tablet of Kliogest for 9 months. Quality of life was assessed using the Greene Climacteric Scale, and the women completed patient preference questionnaires. Treatment with continuous combined therapy was at least as effective as previous sequential regimens in alleviating menopausal symptoms. By the study conclusion, patient preference was strongly in favor of Kliogest with 91% of completers preferring it to their previous sequential therapy. Improved quality of life and patient preference for continuous combined therapy may encourage long-term compliance with treatment, allowing more women to experience the long-term beneficial effects of HRT on osteoporosis and cardiovascular disease.

Aged↗

Effect of graded renal ablation on kidney and serum insulin-like growth factor-I (IGF-I) and IGF binding proteins in rats: relation to compensatory renal growth.

Kidney insulin-like growth factor-I (IGF-I) increases transiently following unilateral nephrectomy, thus preceding the compensatory renal growth. The aim of the present study was to investigate the effect of different degrees (1/7 to 2/3) of renal ablation on kidney and serum IGF-I and IGF binding proteins (IGFBPs) during a 7-day study period. All nephrectomized rats exhibited an increase in the weight of the remaining renal tissue. Kidney IGF-I measured in kidney pieces close to and away from the resected area increased transiently and more significantly away from the resected area, with significant correlation to the amount of tissue resected (day 1, r = .73, P < .0001; day 2, r = .49, P < .05; and day 7, r = .48, P < .05). No changes in kidney IGFBPs or serum IGF-I were observed. Serum IGFBP-4 correlated to the degree of renal resection, as did changes in serum urea and creatinine. In conclusion, significant correlations were observed between local changes in kidney IGF-I and serum IGFBP-4 levels and the degree of renal ablation, suggesting a role for IGF-I as a renotropic factor and, further, that IGFBP-4 is removed to a major extent through the kidney.

Animals↗

Nation-wide Salmonella enterica surveillance and control in Danish slaughter swine herds.

A nation-wide Salmonella enterica surveillance and control programme was initiated in Danish finishing herds over the first quarter of 1995. In Denmark, all swine for slaughter are identifiable by a unique herd code. For each herd code, and depending on the herd's annual kill, random samples ranging from four to more than 60 swine are obtained quarterly at the abattoir. A meat sample from each pig is frozen, and meat juice (harvested after thawing) is examined for specific antibodies against S. enterica using an indirect enzyme-linked immunosorbent assay (ELISA). The ELISA combines several S. enterica O-antigens, and allows detection of antibody response after a variety of different S. enterica serovar infections. Results are transferred to a central database, which each month (based on meat-juice tests obtained in the previous 13 weeks) assigns all herds into three S. enterica infection levels: Level 1, in which the S. enterica prevalence is deemed low and acceptable; Level 2, where there is a moderate prevalence of S. enterica seroreactors (from > 50% in the smallest to > 10% in the largest herds); Level 3, in which S. enterica seroreactor prevalence is clearly unsatisfactory (> 50% for most herd sizes). Irrespective of Salmonella level, all herds receive a monthly update on the current results of the S. enterica test results. If a herd is categorized in Level 2 or 3, it must receive an advisory visit by a practising veterinarian and a local swine extension specialist, and certain management hygiene precautions must be taken. If a herd is categorized in Level 3, the finishers from the herd must additionally be slaughtered under special hygiene precautions. This is supervised by the veterinary authorities. During 1995, 604000 samples were tested for S. enterica, corresponding to 3.0% of the total kill. In December 1995, 15522 herds (representing > 90% of the national production) were categorized into one of the three levels: 14551 herds (93.7%) in Level 1; 610 herds (3.9%) in Level 2; 361 herds (2.3%) in Level 3. The proportion of serologically positive meat-juice samples collected during 1995 ranged from a mean of 2.9% in smaller herds (101-200 swine slaughtered per year) to 6.1% in relatively large herds (more than 5000 swine slaughtered per year).

Abattoirs↗

Corporate management and clinical autonomy: the ethical dilemma in mental health.

Funding constraints and management practices are increasing pressure on clinical autonomy within Australian mental health services. The introduction of total quality management, output-based funding and changes to public mental health policy have promoted business-like efficiency and increased control of resources. It is argued that such moves significantly circumscribe the discretionary authority that mental health professionals have previously enjoyed. This paper attempts to highlight the ethical and moral tension inherent with a corporate management approach, and calls for mental health services to acknowledge the value of intellectual capital, creativity and innovation.

Australia↗

Recombinant factor IX.

Despite the introduction of recombinant preparations of factor VIII and recombinant factor VII and VIIa, patients with other forms of hemophilia, especially hemophilia B, have remained at increased risk for blood borne viruses because of a lack of clinically utilizable preparations of recombinant factor IX. This report describes the state of current tests with a recently licensed preparation of recombinant factor IX, BeneFix, from Genetics Institute. Structurally, functionally, and therapeutically, recombinant factor IX is comparable to monoclonal plasma-derived factor IX. The only observed difference between recombinant and plasma factor IX is the recovery in pharmacokinetic studies where recombinant factor IX recovery was approximately 72% that of a plasma factor IX product. This difference is attributed to be due to minor differences in the post-translational modification of recombinant factor IX compared to plasma. These studies demonstrate that recombinant factor IX is effective in the treatment of hemophilia B and has the safety profile expected from a product prepared by recombinant technology.

Animals↗