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Biomedical subjects

S Johansson

Publications and source records attributed to S Johansson.

At least 55 records · Page 3Linked to original sources

Resonance-enhanced two-photon ionization of ions by Lyman alpha radiation in gaseous nebulae.

One of the mysteries of nebulae in the vicinity of bright stars is the appearance of bright emission spectral lines of ions, which imply fairly high excitation temperatures. We suggest that an ion formation mechanism, based on resonance-enhanced two-photon ionization (RETPI) by intense H Lyman alpha radiation (wavelength of 1215 angstroms) trapped inside optically thick nebulae, can produce these spectral lines. The rate of such an ionization process is high enough for rarefied gaseous media where the recombination rate of the ions formed can be 10(-6) to 10(-8) per second for an electron density of 10(3) to 10(5) per cubic centimeter in the nebula. Under such conditions, the photo-ions formed may subsequently undergo further RETPI, catalyzed by intense He i and He ii radiation, which also gets enhanced in optically thick nebulae that contain enough helium.

Journal Article↗

Left sided vocal cord paralysis: a newly recognized late complication of mediastinal irradiation.

BACKGROUND AND PURPOSE: To evaluate the incidence of vocal cord paralysis in a group of breast cancer patients treated with post operative radiation therapy after radical mastectomy. MATERIALS AND METHODS: A group of 150 patients operated with total mastectomy and axillary clearance received, in 1963-1965, post-operative radiotherapy to the parasternal, axillary and supraclavicular lymph node regions. The cohort has now been followed up to 34 years. RESULTS: Eleven of the 12 vocal cord paralyses were left sided, although the breast cancer was almost equally distributed as left- and right-sided (55 vs. 45%). The symptoms did not appear until 2-25 years after irradiation. Series 1 (treated with (60)Co photons) developed 5% recurrent nerve paralysis (RNP) after a median time of 19.0 years compared with 10% and a much earlier appearance (3.5 years) for series 2 (treated with both (60)Co photons and electrons). A reconstruction of the dose plan shows that an unintentional overlap of the fields resulted in hotspots in the tracheo-oesophageal groove, where parts of the tissue received 120-130% of the prescribed dose. CONCLUSIONS: A left-sided vocal cord paralysis of patients treated with mediastinal radiotherapy might not indicate only tumour recurrence but also mediastinal fibrosis. Small differences in patient positioning cannot be excluded as the cause of the difference in the two series. We postulate that other more subtle damage to the vagus nerve may occur without being recognized as late radiation injury.

Adult↗

Incidence of newly diagnosed heart failure in UK general practice.

AIM: To estimate the incidence rate of heart failure in the general population and to assess risk factors associated with the occurrence of newly diagnosed heart failure. METHODS: From the source population that was derived from the UK General Practice Research Database, we identified patients aged 40--84 years newly diagnosed with heart failure in 1996, and estimated incidence rates. We sent questionnaires to a random sample of heart failure patients (N=1200) and performed a nested case-control analysis to assess risk factors for heart failure. RESULTS: The overall incidence rate for heart failure was 4.4 per 1000 person-years in men and 3.9 per 1000 person-years in women. The incidence increased steeply with age in both sexes. The relative risk of heart failure was 2.1 (95% C.I.: 1.7--2.6) among men compared with women less than 65 years old and 1.3 (95% C.I.: 1.2--1.4) above the age of 65. Slightly more than half of the cases were categorized in NYHA III--IV at the time of the first diagnosis. Within one month of initial diagnosis 62% of the men and 50% of the women were referred to specialists and/or hospitalized for heart failure. Smoking, hypertension, diabetes, obesity were independently associated with heart failure as well as history of distant dyspnoea. Coronary heart disease was the most common cause of heart failure with a greater relative prevalence in men than women. CONCLUSION: Incident heart failure cases mainly comprised elderly men and women frequently burdened with several diseases in general practice. Women had a lower incidence of heart failure than men. However, traditional risk factors such as smoking, hypertension, obesity, diabetes and dyspnoea appeared to confer the same relative increase in heart failure risk among women and men.

Adult↗

Gender and drug treatment as determinants of mortality in a cohort of heart failure patients.

AIM: We assessed gender differences in the risk of mortality in heart failure (HF) patients and evaluated the association between HF drug treatment and mortality. METHODS AND RESULTS: We identified a cohort of 820 patients with newly diagnosed HF in 1996 in UK general practices. The diagnosis of HF was confirmed by the general practitioner. Fifty per cent were females and 27% were less than 70 years old. During a mean follow-up of 2 years, 172 patients died. We used computerized records to assess risk factors and drugs prescribed as treatment. The information on severity was assessed through a questionnaire. We performed a nested case-control analysis, and observed that men had twice the risk of dying than females, however the effect of age on mortality was stronger in females than males. We found a similar interaction between HF severity and sex. Data on use of some cardiovascular drugs such as diuretics, beta-blockers ACE-inhibitors and calcium channel blockers were suggestive of a reduced mortality risk. Current use of nitrates and glycosides carried an increased risk. CONCLUSION: Older age, male sex and severity of HF were the main predictors of mortality among HF patients. Long-term use of beta-blockers was associated with a significantly reduced risk of mortality.

Adult↗

Immunohistochemical localization of retinoid binding proteins at the materno-fetal interface of the porcine epitheliochorial placenta.

Retinol and retinoic acid that are potent modulators of gene expression are vital for development and growth of the conceptus. Apart from being transported across the placenta, retinol and retinoic acid may also be active in the placenta per se. Three proteins involved in 1) serum transport of retinol (retinol binding protein [RBP]), 2) cellular transport and metabolism of retinol (cellular RBP [CRBP] I), and 3) retinoic acid (cellular retinoic acid binding protein [CRABP] I), respectively, have been located by immunohistochemistry during gestation in the porcine placenta. This is a diffuse epitheliochorial placenta composed of areolar-gland subunits, where transport of larger molecules takes place, and interareolar regions, where gas-exchange and trophoblast absorption of hemotroph occur. Immunoreactive-RBP (ir-RBP) as well as CRBP I (ir-CRBP) was detected in uterine glands and in areolar trophoblasts, suggesting that RBP-retinol is secreted by the glands and absorbed by the trophoblasts. Both proteins were present also at the interareolar regions, with ir-CRBP in both the uterine epithelium and the apposing trophoblasts, but ir-RBP only in the former. The localization of ir-CRABP was, in contrast, strictly limited to interareolar trophoblasts. Together these findings suggest that 1) the areolar gland subunits are important for transport of retinol and retinol-RBP, and 2) retinoid binding proteins are involved in the development and growth of the porcine placenta.

Animals↗

Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells.

The saponin digitonin, the aglycone digitoxigenin and five cardiac glycosides were evaluated for cytotoxicity using primary cultures of tumor cells from patients and a human cell line panel (representing different cytotoxic drug-resistance patterns). Of these seven compounds, proscillaridin A was the most potent (IC(50): 6.4--76 nM), followed by digitoxin, and then ouabain, digoxin, lanatoside C, digitoxigenin and digitonin. Correlation analysis of the log IC(50) values for the cell lines in the panel showed that compound cytotoxicity was only slightly influenced by resistance mechanisms that involved P-glycoprotein, topoisomerase II, multidrug resistance-associated protein and glutathione-mediated drug resistance. Digitoxin and digoxin expressed selective toxicity against solid tumor cells from patients, while proscillaridin A expressed no selective toxicity against either solid or hematological tumor cells. The results revealed marked differences in cytotoxicity between the cardiac glycosides, both in potency and selectivity, and modes of action for cytotoxicity that differ from that of commonly used anticancer drugs.

Antineoplastic Agents↗

Prescription drug use, diagnoses, and healthcare utilization among the elderly.

BACKGROUND: More elderly patients affected by severe and chronic diseases are treated in primary care. Reports on the use of prescription drugs by the general elderly population are scarce, and more investigations are needed to optimize pharmaceutical care for these patients. OBJECTIVE: To analyze prescription drug use, diagnoses, and healthcare utilization among noninstitutionalized elderly patients. DESIGN: Retrospective cohort study. SETTING AND PATIENTS: All people > or =65 years old (n = 4642) living in the community of Tierp, Sweden, in 1994 were included. Prescription drug use and healthcare utilization have been registered for all inhabitants of the community since 1972. Information about filled prescriptions and diagnoses were obtained from a computerized research register. RESULTS: Prescription drug use was high among the elderly (78%); the most used pharmacologic groups were cardiovascular, nervous system, and gastrointestinal medications. Women used more prescription drugs than men (average 4.8 vs. 3.8) and had more nonfatal diagnoses. Use of five or more different prescription drugs during 1994 was common (39.0%), and multivariate analysis showed that the greatest number of primary care visits occurred with multiple drug use (> or =5 drugs over 1 y). CONCLUSIONS: This study shows an extensive multiple drug use among elderly people living at home. Whether this multiple drug use per se is harmful to the patients or not could not be evaluated in this study. Further focused investigations are needed to assess the effect of multiple drug use in an elderly population.

Age Distribution↗

Vitamin A antagonizes calcium response to vitamin D in man.

For unknown reasons, the highest incidence of osteoporosis is found in northern Europe. In these populations, the sunlight exposure is limited and the vitamin A intake is high. The interaction between vitamin A and D has been the subject of several in vitro and animal studies. We have studied the acute effects of vitamin A and D on calcium homeostasis in 9 healthy human subjects. We compared the effect of (i) 15 mg of retinyl palmitate, (ii) 2 microg of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], (iii) 15 mg of retinyl palmitate plus 2 microg of 1,25(OH)2D3, and (iv) placebo in a double-blind crossover study. The subjects took vitamin preparations at 10:00 p.m. and the following day blood samples were collected five times from 8:00 a.m. to 4:00 p.m. Serum levels of 1,25(OH)2D3 and retinyl esters increased (1.7-fold and 8.3-fold, respectively; p < 0.01). As expected, serum calcium (S-calcium) increased (2.3%; p < 0.01) and S-parathyroid hormone (PTH) decreased (-32%; p < 0.05) after 1,25(OH)2D3 intake. In contrast, retinyl palmitate intake resulted in a significant decrease in S-calcium when taken alone (-1.0%; p < 0.05) and diminished the calcium response to 1,25(OH)2D3 after the combined intake (1.4%; p < 0.01). S-PTH was unaffected by retinyl palmitate. No significant changes in serum levels of the degradation product of C-telopeptide of type I collagen (CrossLaps), or U-calcium/creatinine levels were found. In conclusion, an intake of vitamin A corresponding to about one serving of liver antagonizes the rapid intestinal calcium response to physiological levels of vitamin D in man.

Adult↗

Giving advice on cost effective measures for a cleaner Baltic Sea: a challenge for science.

The Baltic Sea is one of the world's seas that is most severely affected by human activities. Although there is an international agreement that nutrient input to the Baltic should be reduced, the measures taken so far have not resulted in major reductions in nutrient inputs nor in environmental improvements. The reasons for this are partly due to lack of knowledge on large-scale relationships and couplings between physics, biogeochemistry and ecological properties. But there is also a lack of overall drainage basin-wide analyses on cost-effective measures. There is a danger in making the wrong decisions, e.g. implement reduction schemes that are at worst ineffective or at best, far from cost effective. Researchers from many disciplines are faced with a common challenge: To develop a decision-support system, which can be used as the scientific base for cost-effective measures for the entire Baltic Sea. Such an effort is now being made within the research program MARE (http://www.mare.su.se).

Baltic States↗

[Patent ductus arteriosus. A common clinical problem in extremely premature infants].

An analysis was made of the incidence and treatment regimen of symptomatic patent ductus arteriosus (PDA) in 95 preterm infants treated 1997-1999 in a level three intensive care unit in Stockholm. 47 infants (49 percent) had PDA. Of these 17 infants were managed conservatively (fluid restriction and diuretics), 13 were treated with indomethacin, 10 underwent primary surgical ligation and 7 were treated with indomethacin first and surgery later on. The proportion of infants given "active" therapy (surgery and/or indomethacin) rose from 50 percent in 1997 to 85 percent in 1999. In a stepwise multiple regression analysis low birthweight, septicaemia and need for mechanical ventilation were all independently associated with PDA.

Cyclooxygenase Inhibitors↗

Bone tissue composition, dimensions and strength in female rats given an increased dietary level of vitamin A or exposed to 3,3',4, 4',5-pentachlorobiphenyl (PCB126) alone or in combination with vitamin C.

In previous studies we have described structural and functional changes in rat bone tissue caused by 3,3',4,4',5-pentachlorobiphenyl (PCB126). Some of the effects caused by PCB126 resemble those found in vitamin C-deficient rats, as well as those found in rats with a high dietary intake of vitamin A. The present investigation was designed to determine if these PCB126-induced changes could be inhibited by addition of vitamin C to the drinking water and if they could be evoked by vitamin A administration. Five groups of female rats were used in this study, which lasted for 12 weeks. Three of the groups were exposed to PCB126 (total dose 320 microgram/kg, bw), either alone or in combination with vitamin C added to the drinking water (1 and 10 g/l, respectively). One group was given feed with increased level of vitamin A (600000 U/kg pellet) and the fifth group served as controls. Using peripheral quantitative computed tomography (pQCT), it was found that PCB126 increased trabecular density and cortical thickness, but reduced the trabecular area. Furthermore, maximum torque and stiffness of the humerus during torsional testing and serum osteocalcin levels were reduced by PCB126. Of the PCB126 induced effects observed, addition of vitamin C only inhibited the reduction of serum osteocalcin. Like PCB126 vitamin A supplementation increased the inorganic content and the bone density and also reduced the trabecular area and polar moment of inertia but did not increase the cortical thickness or reduce maximum torque, stiffness or serum osteocalcin level. Apparently, the effects induced by PCB126 are not mediated either via decreased vitamin C level or increased vitamin A level.

Animals↗

Timescale of evolution of late radiation injury after postoperative radiotherapy of breast cancer patients.

PURPOSE: To evaluate the incidence and prevalence of various signs of late morbidity, their time of appearance and pattern of progression during an observation period up to 34 years in breast cancer patients treated with postoperative radiation therapy after radical mastectomy. METHODS AND MATERIALS: A group of 71 breast cancer patients received in 1963-1965 aggressive postoperative telecobalt therapy to the parasternal, axillary, and supraclavicular lymph node regions after total mastectomy and axillary clearance. None of the patients received chemotherapy either prior to, or after the irradiation as part of their primary treatment. The prescribed dose to the three lymph node regions was 44 Gy in 11 fractions. Only two of the three fields were treated per day. This total dose was given in 16-17 fractions over 3-4 weeks. Because of the overlap of the supraclavicular and axillary fields, the dose received by the brachial plexus was not the dose that was prescribed. A retrospective dose calculation showed that the total dose to the brachial plexus was 57 Gy, delivered as a complex combination of 1.8 Gy, 3.4 Gy, and 5.2 Gy fractions. This cohort of patients has now been followed to 34 years and the late side effects of the treatment evaluated and scored. RESULTS: This series is unique in the literature. There is no comparable report of a detailed long-term follow-up in a homogeneously treated group of patients with such a high survival, especially among the younger women, where it is almost 50% at 30 years. This is the reason that they were able to develop some of the very slowly evolving injuries. There was progression of many of the late effects in the period between 5 and 34 years. The more serious morbidities have increased progressively over the whole 34-year follow-up period. Ninety-two percent of the long-term survivors have paralysis of their arm. Other neurological findings included unilateral vocal cord paralysis among 5% of the patients, who developed the disease after a median time of 19 years. All of them were left-sided, indicating a mediastinal involvement of the recurrent nerve. Local recurrence or the appearance of a new primary tumor infiltrating or causing pressure on the recurrent nerve were vigorously investigated and excluded as possible causes of these symptoms. CONCLUSION: The greatest risk for all cancer patients is the inadequate treatment of their disease, because this is inevitably lethal. The aggressiveness of the therapy and the acceptable risk of complications must therefore be balanced against the risk of recurrence. The neuropathy seems to be closely linked to the development of fibrosis around the nerve trunks. The use of large daily fractions, combined with hot spots from overlapping fields contributed to the severity of the complications.

Adult↗

[Fiberoptic endoscopy confirms the cause of upper respiratory obstruction in small children. The most common causes to referrals are sleep apnea syndrome and inspiratory stridor].

Guidelines for the clinical investigation of young children with stridor and sleep apnea are presented. Clinical examination and flexible videolaryngoscopy performed in local anaesthesia are the most important diagnostic tools for this group of children. If the impairment is severe or an objective evaluation is needed the child should also undergo nocturnal polygraphic recording and lung function tests. Out of 43 children examined with flexible videolaryngoscopy 21 had positive findings, laryngomalacia being the most common diagnosis. Flexible videolaryngoscopy is a good complement to laryngoscopy under general anaesthesia. It can be performed as early as in the neonatal period.

Child, Preschool↗

Effects of tobacco smoke on tumor growth and radiation response of dunning R3327 prostate adenocarcinoma in rats.

BACKGROUND: The influence of tobacco smoke has been investigated on the growth rate and histology of prostate cancer, both in untreated tumors and in those subjected to fractionated irradiation. METHODS: Twenty-five rats were implanted bilaterally with Dunning R3327 tumor fragments at 10 weeks of age. Approximately 3 months later, they were randomly allocated to two groups, one of which was exposed to tobacco smoke for an hour each day, 5 days a week. Three weeks later the groups were further subdivided into two groups which acted as controls or were subjected to 5 daily doses of 6 Gy. The tumors were measured weekly to construct growth curves. At a fixed time, 9 weeks or 20 weeks later, the animals were sacrificed and the tumors were removed for histological evaluation of the tissue composition. Sections from each tumor were scored in a morphometric analysis of the fraction of the area of tumor that was occupied by (epithelial) tumor cells, by stroma, or by luminal spaces. In addition, the density of mast cells was assessed in adjacent sections stained with toluidine blue. RESULTS: Smoking caused only minor changes in the growth rates of both the control and the irradiated tumors. At the cellular level, smoking caused a small but significant increase in the fraction of tumor cells relative to controls. Irradiation also caused a small but significant decrease in tumor cell fraction compared to controls, even after 20 weeks of regrowth. This difference was reduced in the smoking and irradiation group. The main difference observed was in the mast cell numbers. Smoking caused a 4-fold increase in mast-cell density. Irradiation caused an even greater increase (25-fold). The combination of smoking and irradiation resulted in an intermediate increase (10-fold). CONCLUSIONS: Long-term smoke exposure can slightly alter the growth rate and morphology of Dunning R3327 rat prostatic adenocarcinoma, but our study does not show a negative effect on the outcome of radiation treatment of this tumor model. We have also demonstrated a highly elevated number of mast cells in the irradiated group, and have shown that smoke exposure significantly depressed the radiation-induced enhancement of the number of mast cells.

Adenocarcinoma↗

Expression of integrin subunit beta1B in integrin beta1-deficient GD25 cells does not interfere with alphaVbeta3 functions.

We have expressed the beta1B integrin subunit in beta1-deficient GD25 cells to examine beta1B functions without the interference of endogenous beta1A expression. As previously reported [Retta et al., 1998, Mol. Biol. Cell 9, 715-731], the beta1B integrins did not mediate cell adhesion under normal culture conditions, while the presence of 0.3 mM Mn(2+) allowed beta1B integrins to support adhesion. Mn(2+), as well as the small soluble peptide GRGDS, induced a beta1B conformation, which was recognized by the mAb 9EG7, a marker for active or ligand-bound integrins. beta1B integrins were found to localize to a subset of focal contacts in a ligand-independent manner on fibronectin, but not on vitronectin. However, clustering of beta1B did not induce tyrosine phosphorylation of FAK, p130(Cas), or paxillin, as studied by beta1B-mediated adhesion, to fibronectin in the presence of Mn(2+) or to anti-beta1 antibody in DMEM. Induction of ligand-occupied conformation by the GRGDS peptide during the adhesion to anti-beta1 antibody also failed to trigger FAK phosphorylation. Stimulation of tyrosine phosphorylation on FAK, p130(Cas), and paxillin by adhesion via integrin alphaVbeta3 to fibronectin or vitronectin was not disturbed in GD25-beta1B cells compared to the untransfected GD25 cells, nor were any negative effects of beta1B observed on alphaVbeta3-mediated cell attachment, spreading, and actin organization, or on the cell proliferation rate. These results show that the reported negative effects of beta1B on adhesive events do not apply to alphaVbeta3-dependent interactions and suggest that they may specifically act on beta1 integrins.

Actins↗