Biomedical subjects
Publications and source records attributed to T Svensson.
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Francisella tularensis is the etiological agent of tularemia, a serious disease in several Northern hemisphere countries. The organism has fastidious growth requirements and is very poorly understood at the genetic and molecular levels. Given the lack of data on this organism, we undertook the sample sequencing of its genome. A random library of DNA fragments from a highly virulent strain (Schu 4) of F. tularensis was constructed and the nucleotide sequences of 13,904 cloned fragments were determined and assembled into 353 contigs. A total of 1.83 Mb of nucleotide sequence was obtained that had a G+C content of 33.2%. Genes located on plasmids pOM1 and pNFL10, which had been previously isolated from low virulence strains of F. tularensis, were absent but all of the other known F. tularensis genes were represented in the assembled data. F. tularensis Schu4 was able to grow in the absence of aromatic amino acids and orthologues of genes which could encode enzymes in the shikimate pathway in other bacteria were identified in the assembled data. Genes that could encode all of the enzymes in the purine biosynthetic and most of the en- zymes in the purine salvage pathways were also identified. This data will be used to develop defined rationally attenuated mutants of F. tularensis, which could be used as replacements for the existing genetically undefined live vaccine strain.
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Most studies of the relation between psychological performance in the elderly and deficiencies of cobalamin and folate have used methods that determine the blood concentrations of these vitamins, which might not reflect the vitamin status in the tissues. Recently, two new markers, plasma homocysteine and methylmalonic acid, have attracted growing interest since they are considered to reflect the status of cobalamins and folates in the tissues. In a previous study, we noted a strong association between five parameters of well-being and lower concentrations of plasma homocysteine. In the present study, we have extended these observations by determination of plasma methylmalonic acid in the same healthy elderly population. In the present study, 18 out of 100 subjects had increased plasma methylmalonic acid and in 7 of these subjects, the concentrations of serum cobalamin, blood folate, plasma homocysteine and serum creatinine were within normal limits. The relation between plasma methylmalonic acid concentrations and concentrations of serum cobalamin and blood folates and five parameters of well-being were investigated. Concentrations of plasma methylmalonic acid were only weakly associated with the concentrations of serum cobalamin and lower scores on the logical reasoning test. The present study clearly shows that the levels of plasma methylmalonic acid show a much lesser association with the parameters of well-being than did plasma homocysteine.
This longitudinal study examines the relationship between family and friend social support, health, and life satisfaction for a single cohort of eighty-year-old persons living in Lund, Sweden. Results indicate that participants who remained in the study are healthier and score higher on life satisfaction when compared with those who either drop-out or die prior to age eighty-three. Even though well-integrated with family and friends, the number of friends decreases significantly from eighty to eighty-three years; those who reported no close friends nearly doubled from eighty to eighty-three years. However, for those with close friends, contact with friends increases with age. In contrast to previous research, a correlational analysis indicates that neither child nor friend support is related to life satisfaction at either eighty or eighty-three years. However, health measures and satisfaction with sibling contact are related to total life satisfaction at age eighty-three only. These findings indicate the multidimensionality of both social support and life satisfaction for the old-old.
In this study, insomnia in 80-year-olds was related to medical, psychological and social factors. The data were based on examinations every year in people aged between 80 and 89 years. Of 333 people living in the city of Lund and born in 1908, 67% participated. Increased severity of insomnia was significantly associated with use of diuretics, other cardiovascular drugs, hypnotics and laxatives, and with nervousness, difficulty relaxing, anorexia, nausea, constipation, backache, feeling cold, sweating, loss of weight, dizziness, depression, general fatigue, exhaustion, angina pectoris, cardiac insufficiency, worsened objective and subjective health, presence of negative T-waves on ECG, anxiety, total life satisfaction, neuroticism, disbelief in a just world, feeling lonely and lower survival rates. Thus insomnia has widespread associations with different aspects of life in 80-year-olds.
Neuroblastoma, a childhood tumour of the sympathetic nervous system, may sometimes regress spontaneously in infants, or progress to a poor clinical outcome despite intensive therapy. Neuroblastomas express neurotrophin receptors and high levels of mRNA for trk-A correlates with favourable outcome, whereas trk-B mRNA is expressed by more unfavourable tumours. Using a sensitive RNase protection assay, mRNA expression for the neurotrophin receptor trk-C was investigated in 50 tumour samples from 45 children at different stages including metastatic and relapsing tumour tissue, out of which 22 were also investigated for trk-A mRNA. Thirty-seven of 43 primary tumours (86%) showed trk-C mRNA with more than 300-fold difference between the highest and the lowest values. A higher trk-C index (trk-C mRNA/GAPDH mRNA) was associated with favourable features such as younger age (P = 0.009-0.003), favourable tumour stage (1, 2 or 4S; P < 0.001) and favourable prognosis (P = 0.044). Better survival probability was shown in children with intermediate or high trk-C index compared with patients with low or undetectable levels (P = 0.031). All localised tumours co-expressed mRNA for trk-A and trk-C receptors. RT-PCR analysis detected mRNA encoding the cytoplasmic trk-C tyrosine kinase region only in favourable neuroblastomas. We conclude that favourable neuroblastoma may express the full-length trk-C receptor while unfavourable tumours, especially those with MYCN amplification, seem to either express no trk-C or truncated trk-C receptors with unknown biological function. Trk-C and possibly its preferred ligand NT-3 may be involved in the biology of favourable neuroblastomas showing apoptosis or differentiation.
OBJECTIVES: To relate elevated blood pressure in 80-year-olds to symptoms, life satisfaction and survival. DESIGN: Examinations of medical, psychological and social factors every year between 80 and 86 years of age. SETTING: Primary health care in the city of Lund in southern Sweden. SUBJECTS: Three-hundred and thirty-three persons living in the city of Lund and born in 1908. Participation rate was 67%. INTERVENTION: Abnormal findings were further examined and treated. MAIN OUTCOME MEASURES: Symptoms, blood pressure, laboratory values, psychological factors, cognition, living conditions, and survival. RESULTS: Hypertension according to the definition used was found in 70%. Women were over-represented (P < 0.05). Amongst persons with alleged hypertension, diuretics (P < 0.001) and 'other cardiovascular drugs' (P < 0.001) were more often used. Analgesics were more often used amongst assessed hypertensives (P < 0.05). Those with assessed hypertension scored better in testing of cognition compared to nonhypertensives (P < 0.05), and less often lived in institutions (P < 0.001). Assessed hypertensives had a better survival than alleged hypertensives during the following 7 years (P < 0.01). CONCLUSIONS: Eighty-year-olds with assessed hypertension in the consulting room showed fewer symptoms and had a better cognition and survival than alleged hypertensives (those with a history of hypertension).
In the assessment of the effects of medical technologies, the focus is most often on the quality of the empirical data. In order to shed light on the question whether medical researchers are really so empirically oriented we conducted the following study. 600 questionnaires were sent by mail to three groups, selected at random: 1) pre-clinical researchers; 2) clinical researchers who received research grants from The Swedish Medical Research Council; and 3) general practitioners. The questionnaire was built around three cases concerning the assessment of the effects of: a) H-2-receptor antagonists, b) coronary by-pass surgery and c) the homeopathic treatment of hay fever. The results indicate that there are rather small differences in how the three groups assessed the three technologies and larger differences within one and the same group concerning different cases. The tendency is that the more one considers that empirical data should be assessed independent of theoretical considerations, the higher are the demands which are placed on the quality and quantity of the empirical documentation, and vice-versa.
The effects of 5-HT2 receptor blockade on the ability of a dopamine (DA) D2 receptor antagonist to produce suppression of conditioned avoidance response (CAR) and to produce catalepsy in rats were examined. It was found that ritanserin (2 mg kg-1 s.c.) enhanced the raclopride (0.1 mg kg-1 s.c.)-induced suppression of CAR without affecting raclopride-induced catalepsy at either maximal (4 mg kg-1 s.c.) or submaximal (0.2 mg kg-1 s.c.) doses. Considering the CAR performance as an index of mesocorticolimbic dopaminergic functions, it is concluded that 5-HT2 receptor blockade confers a limbic profile on the DA D2 receptor antagonist.
Neuroblastoma and its benign counterpart, ganglioneuroma, are tumours of the sympathetic nervous system, and known to produce and release various regulatory peptides. In this study, pancreastatin, a 52 amino acid regulatory peptide derived from chromogranin A, was analysed in plasma and tumour tissue from 15 children with neuroblastoma and one with ganglioneuroma. Detectable pancreastatin immunoreactivity (> 1.9 pmol/l) was found in plasma in 13 of 15 children with highest concentrations in samples from children with favourable outcome (P < 0.05). In tumour tissue, non-metastatic tumours showed higher concentrations of pancreastatin immunoreactivity (P < 0.05). However, the highest concentrations were detected in tumours from children with favourable prognosis, regardless of clinical stage at presentation (P < 0.01). Serial plasma samples from one child with neuroblastoma and one with ganglioneuroma were investigated and showed significant systemic release of pancreastatin immunoreactivity during surgical manipulation of tumours with high pancreastatin concentrations. It is concluded that pancreastatin immunoreactivity may be detected in plasma samples and tumour extracts from children with neuroblastoma and ganglioneuroma. Systemic release during surgery implied tumour origin of elevated plasma pancreastatin. Furthermore, higher pancreastatin concentrations correlate with tumour differentiation, localised clinical stage and a favourable outcome for children with these tumours. It is suggested that pancreastatin in plasma and tumour tissue may be utilised as a marker indicating favourable tumour behaviour.
In conscious rats, intrathecal (i.t.) administration of norepinephrine (NE) produced pressor responses, whereas i.t. epinephrine (Epi) caused depressor responses at low doses (0.1-1 microgram) and pressor responses at a higher dose (10 micrograms). Epi administered i.t. produced bradycardia; however, NE caused tachycardia at low doses and bradycardia at high doses. The cardiovascular responses were dissimilar to those observed after intravenous (i.v.) administration of these doses of NE and Epi. When [3H]NE or [3H]Epi (1.0 microgram, 10 mCi) was injected i.t., minimal radioactivity was detected in peripheral blood (PB) samples, indicating that the effects of i.t.-injected catecholamines on blood pressure (BP) and heart rate (HR) are due to stimulation of central spinal adrenoceptors and not to peripheral effects after leakage. Pretreatment with i.t. administration of the alpha 1-antagonist prazosin (1.0 microgram) attenuated pressor responses and tachycardia produced by i.t. NE (1.0 microgram), whereas i.t. pretreatment with the alpha 2-antagonist yohimbine (10 micrograms) counteracted depressor responses and bradycardia produced by i.t. Epi. Therefore, these spinally released catecholamines appear to produce opposite cardiovascular effects whereby sympathetic preganglionic neurons are excited by NE through spinal alpha 1-adrenoceptors and are inhibited by Epi through spinal alpha 2-adrenoceptors.
In the present paper, the attitudes of three different groups of physicians toward treatment with alternative medicine have been investigated. One of the groups studied consisted of randomly selected licensed physicians from the Swedish National Board of Health and Welfare. The other two groups comprised two different associations of physicians involved with alternative medicine. One third of the former groups were positively disposed toward one or more of the alternative medical technologies, while the latter groups were more positive toward alternative medicine in general. Attitudes, along with motives for such interest, varied depending on the orientations of the different interest groups. The most common motives for expressing interest in alternative medicine included a feeling of clinical powerlessness in the face of certain problems for which patients consult a physician, and a dissatisfaction with the scientific approach of academic medicine. A minority stated that their interest in alternative medicine pre-dated their medical education. Physicians' interest in alternative medicine can be understood both as a critical reaction to academic medicine and as evidence that some alternative medical technologies are effective. Hence there is a need to determine whether there are shortcomings to be found in academic medical education and scientific ideals, and also to assess alternative medical technologies at regular intervals.
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Today different issues of medical ethics are in focus of the debate. A theoretical sequence starting at a "prepathogenic" level, ending in terminal care, is delineated to clarify the different characteristics of medical interventions. In this article we will discuss some ethical problems concerning interventions in the first parts of this sequence. Preventive measures at the population level are contrasted to the situation when the patient feels ill and calls for an intervention. Certain elements of paternalism are often interwoven in preventive medicine and health promotion.-The field of preventive medicine calls for a vivid theoretical and ethical discussion, which can mean better opportunities for effective prevention.
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