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Biomedical subjects

S Kjaergaard

Publications and source records attributed to S Kjaergaard.

27 records · Page 2Linked to original sources

Oral ingestion of mannose elevates blood mannose levels: a first step toward a potential therapy for carbohydrate-deficient glycoprotein syndrome type I.

Carbohydrate-deficient glycoprotein syndrome type I (CDGS) is an inherited metabolic disorder with multisystemic abnormalities resulting from a failure to add entire N-linked oligosaccharide chains to many glycoproteins. Fibroblasts from these patients also abnormally glycosylate proteins, but this lesion is corrected by providing 250 microM mannose to the culture medium. This correction of protein glycosylation suggests that providing dietary mannose to elevate blood mannose concentrations might also remedy some of the underglycosylation observed in these patients. We find that ingested mannose is efficiently absorbed and increases blood mannose levels in both normal subjects and CDGS patients. Blood mannose levels increased in a dose-dependent fashion with increasing oral doses of mannose (0.07-0.21 g mannose/kg body weight). Peak blood mannose concentrations occurred at 1-2 h following ingestion and the clearance half-time was approximately 4 h. Doses of 0.1 g mannose/ kg body weight given at 3-h intervals maintained blood mannose concentrations at levels 3- to 5-fold higher than the basal level in both normal controls (approximately 55 microM) and CDGS patients. No side effects were observed for this dosage regimen. These results establish the feasibility of using mannose as a potential therapeutic dietary supplement (nutraceutical) to treat CDGS patients.

Administration, Oral↗

Nitrogen dioxide in indoor ice skating facilities: an international survey.

An international survey of nitrogen dioxide (NO2) levels inside indoor ice skating facilities was conducted. One-week average NO2 concentrations were measured inside and outside of 332 ice rinks located in nine countries. Each rink manager also completed a questionnaire describing the building, the resurfacing machines, and their use patterns. The (arithmetic) mean NO2 level for all rinks in the study was 228 ppb, with a range of 1-2,680 ppb, based on a sample collected at breathing height and adjacent to the ice surface. The mean of the second indoor sample (collected at a spectator's area) was 221 ppb, with a range of 1-3,175 ppb. The ratio of the indoor to outdoor NO2 concentrations was above 1 for 95% of the rinks sampled, indicating the presence of an indoor NO2 source (mean indoor:outdoor ratio = 20). Estimates of short-term NO2 concentrations indicated that as many as 40% of the sampled rinks would have exceeded the World Health Organization 1-hour guideline value of 213 ppb NO2 for indoor air. Statistically significant associations were observed between NO2 levels and the type of fuel used to power the resurfacer, the absence of a catalytic converter on a resurfacer, and the use of an ice edger. There were also indications that decreased use of mechanical ventilation, increased number of resurfacing operations per day, and smaller rink volumes were associated with increased NO2 levels. In rinks where the main resurfacer was powered by propane, the NO2 concentrations were higher than in those with gasoline-powered resurfacers, while the latter had NO2 concentrations higher than in those using diesel. Rinks where the main resurfacer was electric had the lowest indoor NO2 concentrations, similar to the levels measured outdoors.

Air Pollution, Indoor↗

Effect of graduated intravenous and standard rectal doses of indomethacin on cerebral blood flow in healthy volunteers.

Administration of indomethacin may aid treatment of intracranial hypertension, and the present study was conducted to determine the optimal dose. In healthy volunteers, cerebral blood flow (CBF) has been shown to decrease considerably after a bolus dose of indomethacin, 0.4 mg/kg, followed by continuous infusion, 0.4 mg/kg/h. This decrease was sustained for 6 h without any evidence of adaptation. In a randomized study in healthy volunteers, indomethacin, 0.1, 0.2, and 0.3 mg/kg, was given as bolus, followed by continuous infusion of 0.1, 0.2, and 0.3 mg/kg/h. CBF decreased from normal levels (52-74 ml/100 mg/min) to 38-51 ml/100 g/min. There were no differences among the three groups in CBF reduction, and the reduction was sustained during the 6-h infusion period. Rectal application of 100 mg indomethacin was found to reduce CBF from normal levels (54-74 ml/100 mg/min) to 33-48 ml/100 mg/min. These low levels were only sustained for 2 h, and values returned to normal over the next 6 h. We observed no rebound phenomenon 2 h after stopping the infusion and no rebound after 100 mg of rectally applied indomethacin. Since a dose as low as 0.1 mg/kg/h is effective, it is possible to treat most patients in a 24-h schedule without going over maximum recommended doses.

Administration, Rectal↗

Effects of nitrous acid exposure on human mucous membranes.

Nitrous acid (HONO) is formed both indirectly from the reaction of nitrogen dioxide (NO2) with water on indoor surfaces, and directly during combustion. This gaseous pollutant may be a previously unrecognized causal factor in assessments of nitrogen oxide exposure effects. The present study is the first attempt to evaluate exposure effects of HONO on the human airways and the mucous membranes of the eyes and nose. Fifteen healthy adult nonsmokers were exposed for 3.5 h in a double-blind, balanced protocol to clean air, 77, and 395 ppb HONO. Each exposure was preceded by a 1-h baseline measurement period, and exposures were separated by 1 wk. There was a 10-min exercise period during exposure. Effects measurements included assessment of bronchial reactivity, measurement of specific airway conductance, spirometry, acoustic rhinometry, nasal lavage, tear-fluid cytology, a CO2 eye-provocation test, evaluation of eye redness, and subjective sensations. Effects of HONO exposure on the eyes were found as exposure-related changes in tear-fluid cytology. In particular, the number of squamous cells increased by 20, 67, and 80% following exposure to clean air, 77, and 395 ppb HONO, respectively (p = 0.004). Possible indications of exposure effects on sensitivity to CO2 eye provocation and on specific airway conductance were also measured. For specific airway conductance there was an approximate 10% decrease in conductance following exercise in association with HONO exposure, compared with a 2% decrease with clean air (p = 0.038).

Adult↗

Absence of homozygosity for predominant mutations in PMM2 in Danish patients with carbohydrate-deficient glycoprotein syndrome type 1.

Carbohydrate-deficient glycoprotein syndrome type 1 (CDG1; McKusick No. 212065) is an autosomal recessively inherited disease characterised clinically by central nervous system dysfunction and biochemically by hypoglycosylation of many serum proteins. Most patients with CDG1 have deficient activity of phosphomannomutase. The locus for this enzyme has been mapped to 16p13, and a gene, PMM2, encoding phosphomannomutase has been isolated. We identified 34 mutations on 36 disease chromosomes in 18 unrelated Danish patients with CDG1. All patients have less than 15% residual activity of phosphomannomutase. Two mutations account for 88% of all mutations: F119L and R141H were each found in 16 out of 36 CDG1 alleles. These two mutations were found to be in linkage disequilibrium with two different alleles of the marker D16S3020, suggesting that there is one ancestral origin for each mutation. Two new mutations, G117R and D223E, were identified also. Surprisingly, no patient was homozygous for either of the two common mutations, suggesting that homozygosity for these mutations is either lethal or so benign that such patients are not detected.

Base Sequence↗

Sensitivity of the eyes to airborne irritant stimuli: influence of individual characteristics.

The purpose of this study was to measure trigeminal sensitivity of the eyes to irritative exposures and to examine the influence of individual characteristics, e.g., gender, age, and smoking, on this sensitivity. During an experimental study, 158 of 2,025 randomly selected volunteers were examined for sensory irritation threshold in the eyes to carbon dioxide (CO2). Eyes were exposed to progressive concentrations of CO2 (10, 20, 40, 80, and 160 ml/l), until the subject claimed a distinct irritation. Each exposure level lasted 2 min. A special exposure mask system was used for eyes-only exposure. No significant dependence of gender or smoking was found, but subjects who were less than 40 y of age were more sensitive than were the elderly subjects. Subjects who reported frequent "sick building syndrome" irritation symptoms had lower thresholds (i.e., higher sensitivity). The CO2 threshold was related to skin irritation sensitivity, i.e., response to lactic acid smeared on the cheek, and there were indications that occupational stress was associated with low thresholds. Studies of irritation to n-decane indicate that the CO2 threshold may be an important factor in the prediction of individual sensitivity to irritation from airborne pollutants. The CO2 threshold of the eyes may be of value in the evaluation of hypersensitivity to indoor air pollution. Furthermore, the threshold may be used to assess important relationships between the different trigeminal innervated areas, e.g., skin and eyes. Finally, the method has the advantage of avoiding interference from olfactory stimulation.

Adolescent↗

Clinical and patient based evaluation of immunotherapy for grass pollen and mite allergy.

BACKGROUND: Treatment of allergic disease can be done by pharmacological intervention by allergen avoidance--in the following called standard care (SC), or by specific treatment with allergy vaccination; Specific Immunotherapy (SIT). The aim of this study were to evaluate the effects of subcutaneously administrated SIT compared to SC by objective (clinical/medical records) and subjective parameters (patient's opinion) in a before/after SIT study. METHODS: The study included retrospectively all grass- and mite allergic 16-60 year old patients (N = 253) who had started SIT for grass pollen or mite allergy during the period 1.1.1996-1.1.2002 at The Allergy Unit, Aarhus University Hospital, or at a specialist practice in Aarhus. Relevant data were collected before/after treatment from medical records and from a specific designed questionnaire. The following indicators for effect were applied: Success of immunotherapy expressed as completion of up dosing phase, change in symptoms, a comparison of overall rhinoconjunctivitis symptoms, number of symptom free days per year, effect of pharmaceuticals, change in physical and psychological wellbeing and number of lost days from work/education and leisure activities. RESULTS: Compliance for completed up dosing for SIT was 94 % (95 % CI 90-97). The questionnaire revealed that after SIT there were a significant reduction in degree of symptoms, 84 % (95 % CI 79-89) of the respondents achieved a reduction in over all rhinoconjunctivitis score, there were an increase in symptom free days per year, a decrease in days off/incapacity from work/education and leisure activities, an improved effect of the pharmaceuticals used for allergic symptoms and an improvement in physical and psychological wellbeing. The study also showed that SIT was more effective treating rhinoconjunctivitis symptoms than lung symptoms. CONCLUSION: The study revealed great advantages of SIT compared to SC and a high compliance for SIT during the up dosing period.

Adolescent↗