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Biomedical subjects

B Jonsson

Publications and source records attributed to B Jonsson.

At least 37 records · Page 2Linked to original sources

On the mechanism underlying calcein-induced cytotoxicity.

The cellular pharmacology of calcein acetoxymethyl ester (calcein/AM)-induced cytotoxicity was investigated in human tumor cell lines in order to identify tentative mechanisms of action. The activity profile in 10 cell lines with known mechanisms of resistance was compared with the activity profiles of standard drugs and experimental substances. The activity of calcein correlated with that of different topo II inhibitor/intercalating compounds and mitochondrial accumulating compounds, such as Rhodamine 123, Mito Fluor Green and Acridine Orange-10. Using U-937 GTB as a model cell line, calcein was found to distribute throughout the whole cell, nuclei and mitochondria included. In addition, studies of mitochondrial dehydrogenase activity and extracellular acidification rate showed an almost complete lack of dehydrogenase activity and extracellular acidification at 12 and 24 h, respectively. The results indicate that calcein/AM may induce cytotoxicity through interference with both mitochondrial and nuclear DNA.

Coloring Agents↗

[Lung function in premature infants can be improved. Surfactant therapy and CPAP reduce the need of respiratory support].

Randomised trials have shown exogenous surfactant therapy to reduce mortality and morbidity among very low birthweight (VLBW) infants with respiratory distress syndrome (RDS). Surfactant therapy is normally given to infants on mechanical ventilation. In the Stockholm area, 12 VLBW infants born after 27-30 gestational weeks and suffering from RDS were recently treated using the INSURE (Intubation-SURfactant-Extubation) approach--i.e., surfactant therapy during brief intubation, immediately followed by extubation and continuous positive airway pressure (CPAP) treatment. The treatment was successful in all 12 cases, the mean (+/- SD) a/A ratio increasing significantly from 0.17 +/- 0.04 before the INSURE procedure to 0.46 (0.12 after (P < 0.001). Only one infant later needed mechanical ventilation for RDS.

Blood Gas Analysis↗

Effect and offset of effect of treatments for hip fracture on health outcomes.

We investigated the cost-effectiveness of treatments that reduce the risk of hip fracture using a computer simulation model. Cost-effectiveness was measured as cost per quality-adjusted life-year (QALY) gained using a threshold value for cost-effectiveness of $30,000/QALY gained. The baseline simulations assumed a 5-year intervention that reduced the risk of hip fracture by 50% during the intervention period, and an effect which reversed to the pretreatment risk during the next 5 years. Sensitivity analyses included the effects of age, different fracture risks, and different treatment costs and duration of therapeutic effect once treatment was stopped. Cost-effectiveness was critically dependent upon absolute risk determined by the age and the relative risk of hip fracture at any given age. Reasonable cost-effectiveness was shown even with relatively high intervention costs for women with a risk about twice the average at the age of 70 or more years. Cost-effectiveness was critically dependent upon the assumptions made concerning offset of effect of intervention after the end of treatment. Where no residual effect was assumed, it was difficult to show cost-effectiveness from any intervention except for the most effective and least expensive. Conversely, cost-effectiveness improved considerably where effectiveness persisted for a longer time. These studies support the view that intervention in the elderly with agents affecting skeletal metabolism alone may be preferred to such interventions at the time of the menopause, and that offset time, hitherto poorly characterized, is a critical component of cost-effectiveness, particularly in younger women.

Age Factors↗

Materials emission of chemicals--PVC flooring materials.

Data of chemical emissions from flooring materials have been collected and investigated in a database known as METS. The emission tests are performed using the Field and Laboratory Emission Cell (FLEC). The emission rates of total volatile organic compounds (TVOC) in the boiling point range of hexane to octadecane varies from around 4,000 micrograms/(m2.h) to less than 10 micrograms/(m2.h). Results obtained 1994/95 are presented and compared with the results obtained in 1992 for similar materials. The tests are performed 4 weeks and 26 weeks after the manufacturing of the material. The emission rates of TVOC decrease on the average approximately 60% from 4 to 26 weeks. The differences and trends in emission rates of individual chemicals and their use are discussed. For many VOCs emission rates decrease rapidly and become near to or below 2 micrograms/(m2.h) (the detection limit) after 26 weeks. For a small number of individual compounds the emission rate decrease little over 26 weeks. A small number of chemicals are singled out for particular interest in a health and comfort evaluation based on the emission results.

Air Pollution, Indoor↗

Intellectual and physical performance and morbidity in relation to height in a cohort of 18-year-old Swedish conscripts.

To test whether short stature in young men without malformations or chronic childhood diseases is associated with intellectual and physical performance and morbidity, a large cohort of apparently healthy 18-year-old Swedish men was analysed. The original cohort consisted of all men born in 1976 and conscripted in 1994 (n = 38, 900). After exclusion due to growth-affecting disorders or missing data, 32,887 subjects were available for analysis. Short conscripts (height below or equal to -2 SD scores) demonstrated increased overall morbidity compared with taller conscripts (above -2 SD scores). Specifically, short conscripts had more psychiatric and musculoskeletal diagnoses and were more often considered psychologically unsuitable for military service. Mean intellectual performance increased continuously with height; the mean 'standard nine' score was 4.22 for the short men and 5.17 for the rest (p < 0. 001). Short conscripts scored less well than taller conscripts in assessment of psychological functioning during mental stress, and were evaluated as less suitable for leadership positions. Maximal working capacity per kilogramme body weight correlated negatively with height (p < 0.001). In conclusion, short stature was associated with increased morbidity and psychological problems and with lower mean intellectual performance. To what extent this association is direct or indirect needs further evaluation.

Adolescent↗

Prediction of male adult stature using anthropometric data at birth: a nationwide population-based study.

Short stature and excess weight in adulthood are both associated with an increased risk of health problems. In a population-based investigation, data on birth length, birth weight, and gestational age for males born in Sweden in 1976 were used to predict the risk of being short or overweight in adulthood. The Swedish Birth Register was used to identify singleton males, born to Nordic mothers, who were without malformations and alive at 18 y of age. After individual record linkage between the Birth Register and the Swedish Conscript Register, information about height and weight at 18-21 y was obtained for 90% (n = 39901) of the birth cohort. Logistic regression analyses were used to estimate the risk of being short or overweight at conscription. The odds ratio (OR) was used to estimate relative risk. At conscription, mean height (+/-SD) was 179.5+/-6.6 cm, mean weight 72.1+/-11.2 kg, and mean body mass index 22.3+/-3.1 kg/m2. The risk of short adult stature (<166.3 cm) was associated with being short for gestational age (OR = 5.9), having a low birth weight for gestational age (OR = 1.7), and being born at a gestational age below 32 wk (OR = 2.6). The risk of being overweight (body mass index > +2 SD) was primarily associated with a high ponderal index (> +2 SD; OR = 1.8). In conclusion, anthropometric birth data are better predictors of short stature than of being overweight in adulthood. Among anthropometric data at birth, birth length is the most important predictor of adult height.

Adolescent↗

Lifetime risk of hip fractures is underestimated.

Estimates of lifetime risk of osteoporotic fracture have assumed that mortality rates do not change. Since mortality in the elderly is decreasing in all regions of the world we assessed the effect of this on lifetime risks for hip fracture using Sweden as a reference country. Lifetime risks of hip fracture at the age of 50 years were 4.6% and 13.9% in men and women respectively, assuming all survive to current average life expectancy. Estimates increased to 8.1% and 19.5% when based on present mortality and to 11.1% and 22.7% respectively based on predicted mortality. We conclude that lifetime risks of hip fracture have been considerably underestimated.

Aged↗

The coupling of head, reach and grasp movement in nine months old infant prehension.

In 9-month-old-infants adjustments in the reaching pattern to sudden changes in object location were examined. An attractive ball was presented to the infants at their midline and on some trials (perturbation trials) the ball suddenly changed position 15 cm to the right or left during the reach. For the perturbed trials the movement times approximately doubled compared to the control trials and significantly fewer balls were grasped. The results indicate that infants need to finish the first movement before being able to redirect the reach to a new destination. The correlation between the latency of the head and hand adjustment to the perturbation were 0.85 and 0.78 for movements to the left and to the right, respectively, indicating a tight coupling. The time between the start of the perturbation and peak velocity (TPPV) was significantly shorter for the head movement than for the hand movement, indicating that the head is leading the hand.

Age Factors↗

Endogenous nitric oxide in the upper airways of premature and term infants.

Concentrations of endogenous nitric oxide (NO) were measured in premature (n = 18) and term infants (n = 7). Nasal gas was aspirated continuously and after timed occlusions, 15 s and 60 s, by a fast-response chemiluminescence analyser. The sampling flow rate was 20 ml min-1. Typical NO recordings consisted of plateaux and postocclusive peaks. In term infants peak NO concentrations (60 s occlusion) were 2.71 +/- 0.44 parts per million (ppm) within 10 min after birth, increasing (p < 0.05) to 3.81 +/- 0.25 ppm at 4-7 d postnatally. Peak NO values (15 s occlusion) averaged 1.22 +/- 0.16 ppm in premature infants (postconceptional age 25-37 weeks, body weight 623-2844 g) and the NO concentrations increased significantly with postconceptional age (p < 0.05). Nasal excretion rate, estimated from plateau NO concentrations and sampling flow rate, was 0.10 +/- 0.01 nmol min-1 kg-1 in both groups. We conclude that premature and term newborn infants excrete considerable amounts of NO in the upper airways, with hitherto not fully known functions.

Cross-Sectional Studies↗

Growth hormone treatment of short children born small for gestational age: reappraisal of the rate of bone maturation over 2 years and metanalysis of height gain over 4 years.

A minority of children born small for gestational age (SGA) fail to achieve sufficient catch-up growth during infancy and remain short throughout childhood, apparently without being growth hormone (GH) deficient. A previous metanalysis of four trials revealed that GH treatment over a period of 2 years induced a dose-dependent acceleration of linear growth and, to a lesser extent, of the rate of bone maturation in short, prepubertal children born SGA. The rate of bone maturation and the change in height SDS for bone age from the previous 2-year metanalysis have been re-analysed according to chronological age (two prepubertal age groups: group A, 3.0-5.9 years old; group B, 6.0-8.9 years old). The rate of bone maturation was slower in younger than in older prepubertal children; this difference was more marked in children receiving high-dose (0.2 or 0.3 IU/kg/day) GH treatment (p < or = 0.01). Accordingly, the change in height SDS for bone age was increased by high-dose GH treatment in both age groups (p < or = 0.01), and was more pronounced in younger than in older children (1.45 +/- 0.28 versus 0.63 +/- 0.20; p < or = 0.01). Height SDS data from 100 short, prepubertal children born SGA have been analysed over 4 years. The change in height SDS appeared to be related to the average dose of GH. A mean GH dose of 0.1 IU/kg/day over 4 years was administered either as 0.1 IU/kg/day for 4 years (continuous) or as 0.2 IU/kg/day for 2 years, followed by 2 years without GH treatment (discontinuous). After 4 years of treatment, the increase in height SDS for the continuous and discontinuous treatment schedules was similar, being 1.42 +/- 0.10 SDS and 1.58 +/- 0.17 SDS, respectively. In a second regimen, a mean GH dose of 0.2 IU/kg/day over 3 years was administered either as 0.2 IU/kg/day for 3 years (continuous) or as 0.3 IU/kg/day for 2 years, followed by 1 year without GH treatment (discontinuous). After 3 years, the increase in height SDS with the continuous and discontinuous treatment schedules was similar, being 2.01 +/- 0.18 SDS and 2.22 +/- 0.16 SDS, respectively. GH administration was well tolerated in all treatment groups. In conclusion, the rate of bone maturation in short, prepubertal children born SGA treated with GH appeared to depend not only on the dose of GH, but also on the age of the child. GH treatment resulted in a prolonged increase in height SDS, the magnitude of the rise being dependent on the average GH dose rather than on the continuous or discontinuous mode of GH administration.

Body Height↗

Growth hormone treatment induces a dose-dependent catch-up growth in short children born small for gestational age: a summary of four clinical trials.

In the present study, data from 230 short children born small for gestational age, who were participating in four clinical trials, were pooled and analysed. At the start of GH treatment, median age and height SDS were 5.3 years and -3.2 SDS, respectively. A dose-dependent increase in height SDS was observed following 2 years of GH treatment: 1.1, 1.7 and 2.5 SDS for the three GH treatment groups (0.1, 0.2 and 0.3 IU/kg/day, respectively), compared with an increase of 0.14 SDS in the control group. In a multiple regression analysis, four variables were found to correlate independently with the gain in height SDS following 2 years of GH treatment. These are given below in order of importance: gain in height SDS = 7.7 x dose of GH (IU/kg/day) -0.11 x age (years) -0.08 x parental-adjusted height SDS + 0.05 x birth length SDS (SD = 0.5; r2 = 0.64). At the end of the 2-year study period, a total of 48%, 66% and 90% of patients in the groups given GH at 0.1, 0.2 and 0.3 IU/kg/day, respectively, had a parental-adjusted height greater than -1.0 SDS.

Body Height↗

Cytotoxic activity of calcein acetoxymethyl ester (Calcein/AM) on primary cultures of human haematological and solid tumours.

The aim of this study was to determine the in vitro cytotoxicity of calcein acetoxymethyl ester (Calcein/AM) on primary cultures derived from solid and haematological human tumours. Calcein/AM is a fluorescent dye that localises intracellularly after esterase-dependent cellular trapping and which has shown cytotoxic activity against various established human tumour cell lines at relatively low concentrations. The semi-automated fluorometric microculture cytotoxicity assay, based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate to fluorescein, in microtitre plates was used for the evaluation of Calcein/AM activity in tumour cell suspensions from patients. The cytotoxicity was measured as a survival index (SI), defined as the fluorescence as a percentage of control cultures. A total of 163 evaluable samples from various tumours were tested with continuous drug exposure. The activity of Calcein/AM was compared with representatives of six major classes of standard chemotherapeutic drugs. Calcein/AM was found to induce concentration-dependent decreases in the SI of both haematological and solid tumour cells. The ratio of solid over haematological tumour activity increased at a rate that was concentration dependent. Although it was relatively less active than cisplatin against solid tumours, Calcein/AM showed higher solid tumour activity compared to leukaemic specific agents (cytarabine and amsacrine), vincristine and doxorubicin (Dox). Among the solid tumours tested, childhood tumours, non-small cell lung cancer and sarcomas were the most sensitive to Calcein/AM. The best correlation between SI values was seen between Calcein/AM and Dox, with weaker correlations to representatives of antimetabolites, platinum compounds, topoisomerase II inhibitors, tubulin interactive agents and alkylators. Non-cytotoxic concentrations of cyclosporin A significantly potentiated calcein-induced cytotoxicity. The results show that Calcein/AM is differentially active against haematological tumours, but with substantial activity against solid tumours. The drug may represent a new class of anticancer compound with a unique means of drug delivery.

Antineoplastic Agents↗

A cost-minimization analysis of laparoscopic cholecystectomy versus open cholecystectomy.

BACKGROUND: Earlier economic analyses have evaluated charges but not costs, and have not considered the cost of production losses associated with open and laparoscopic cholecystectomy. This study attempted to accomplish an economic evaluation of open versus laparoscopic cholecystectomy from the point of view of society. METHODS: A cost-minimization analysis, using a clinical decision model, was performed. The data used were taken from different clinical studies, Swedish national registers, local patient statistics, and hospital accounting systems. The direct and indirect costs were measured. RESULTS: Laparoscopic cholecystectomy resulted in cost savings per patient amounting to about 2,400 SEK (as of 31 August 1994, Pound = 11.90 SEK; $1 = 7.76 SEK) compared with open surgery. CONCLUSIONS: From the point of view of society, laparoscopic cholecystectomy was a cost-saving strategy if at least 68 patients were operated on yearly. However, with regard to hospital costs, open cholecystectomy was less expensive than laparoscopic cholecystectomy.

Cholecystectomy↗

Outcome of symptomatic leg ischaemia: four year morbidity and mortality in Vadstena, Sweden.

OBJECTIVE: To quantify cardiovascular morbidity and mortality including the incidence of vascular surgery and amputations, among individuals with symptomatic leg ischaemia. DESIGN: Prospective cohort study. MATERIAL: Inhabitants 50-89 years of age (n = 2784) of Vadstena community, Ostergötland, Sweden, with 4 years of follow-up. 107 subjects with symptomatic leg ischaemia (SLI), selected by a postal questionnaire and ankle pressure measurements, and an age and sex matched control group of 214 individuals. CHIEF OUTCOME MEASURES: Cardiovascular morbidity and mortality, all cause mortality, surgical procedures for leg ischaemia, major amputations, ankle brachial pressure index. MAIN RESULTS: Age and sex adjusted all-cause mortality risk in the SLI-group was increased by 1.9. This was most prominent among men in their sixties and women in their seventies. Cardiovascular mortality was increased by 1.9 (95% confidence interval 1.1-3.3). Relative risks for acute myocardial infarction and cerebrovascular events were 2.4 (1.1-5.1) and 1.7 (0.9-3.2), respectively. The increase in age and sex adjusted incidence of primary reconstructive surgery during the first year after initial examination was 67-fold compared to the total population of Vadstena 50-89 years old, and 18 fold for the whole observation period, while the increase in risk for major amputation during the observation period was 12-fold. Median ankle brachial index improved significantly during follow-up among the individuals alive and not subjected to vascular surgery. CONCLUSIONS: Among the SLI-subjects identified in a general population, the overall risk for cardiovascular morbidity and mortality over 4 years was significantly increased compared to normals.

Age Distribution↗

Amphetamine addiction during pregnancy: 14-year follow-up of growth and school performance.

Sixty-five children born to women who all abused amphetamine during pregnancy have been followed prospectively since their birth in 1976-77. At the age of 14-15 years, information about growth and school achievement was collected from school records. For comparison of school achievements the means of schoolmates were used, and for growth a group of Stockholm children born in the same year. By the age of 14 years only 14 children (22%) had stayed with their biological mothers for the whole period since birth. In the eighth grade, 10 (15%) were one grade lower than indicated by their biological age. The norm for Sweden is less than 5%. The means of the points in mathematics, Swedish language and sports were statistically below those of their classmates. At the age of 10 years the girls were significantly shorter and lighter than their peers born in 1976. At the age of 14 years the boys were statistically taller and heavier than their peers. It can be concluded that maternal amphetamine abuse during pregnancy will influence children at lest up to the age of 14-15 years even though many of them have been living in foster homes since a young age.

Adult↗

Growth hormone treatment of short children born small for gestational age: metanalysis of four independent, randomized, controlled, multicentre studies.

A minority of children born small for gestational age (SGA) fail to achieve sufficient catch-up growth during infancy and remain short throughout childhood, apparently without being growth hormone (GH) deficient. The effect of GH administration was evaluated over 2 years in short prepubertal children born SGA. The children (n = 244), who were taking part in four independent multicentre studies, had been randomly allocated to groups receiving either no treatment or GH treatment at a daily dose of 0.1, 0.2 or 0.3 IU/kg (0.033, 0.067 or 0.1 mg/kg) s.c. At birth, their mean length SD score (SDS) was -3.6 and their mean weight SDS -2.6; at the start of the study, mean age was 5.2 years, bone age 3.8 years, height SDS -3.3, height SDS adjusted for parental height -2.4, weight SDS -4.7 and body mass index (BMI) SDS -1.4. The untreated children had a low-normal growth velocity and poor weight gain. Although bone maturation progressed more slowly than chronological age, final height prognosis tended to decrease, according to height SDS for bone age, GH treatment induced a dose-dependent effect on growth, up to a near doubling of height velocity and weight gain; BMI SDS was not altered. Bone maturation was also accelerated differentially; however, final height prognosis increased in all GH treatment groups. The more pronounced growth responses were observed in younger children with a lower height and weight SDS. In conclusion, GH administration is a promising therapy for normalizing short stature and low weight after insufficient catch-up growth in children born SGA. Long-term strategies incorporating GH therapy now remain to be established.

Age Determination by Skeleton↗