Prehospital management of patients with acute coronary syndromes.
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Biomedical subjects
Publications and source records attributed to L Svensson.
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A prospective study was performed on 185 children with symptomatic urinary tract infection (UTI), 130F and 55M, having a median age of 0.9 y (range 0.1-9.8) at the time of UTI. The aim of the study was to find out how the 99mTechnetium-dimercaptosuccinic acid (DMSA) scan should be used to investigate UTI, and to follow the development of renal changes during pyelonephritis into subsequent permanent renal damage. All children were investigated with a DMSA scan within 5 days after admission and after 3.9-53.3 (median 9.2) weeks, and 159 were studied again after approximately 2 y (range 1.5-3.9 y). They all underwent micturition cystourethrography at the time of the second study. At the time of infection, the DMSA scan was abnormal in 85% of the children, in 58% at the first follow-up and in 36% at the second follow-up. An abnormal DMSA scan performed within 20 weeks from infection became normal in 38% of cases on the third study, while only 1/10 abnormal DMSA scans performed more than 20 weeks after infection became normal after 1.5-3.9 y. Persistent renal changes were more common in children > 4 y of age than in children < or = 1 y of age. Two months after the presenting infection, it was unusual to see a normal DMSA scan in a child with a VUR gr. > or = 3. The study suggests that DMSA changes after an index UTI may be transient for a longer period of time than has been previously considered. Therefore, in order to detect persistent changes, a DMSA scan should be performed more than 5 months after UTI.
OBJECTIVES: To examine the socio-economic effects of team-based clinical case management of patients with chronic minor disease bound for early retirement. DESIGN: Marginal analysis of programme costs and benefits to society compared with no-programme baseline of costs occurring in society due to productivity loss. Prospective patient data collection on admission, discharge, and at one year and five years after discharge to determine programme effectiveness. SETTING: Out-patient clinic at the department of social medicine in tertiary care hospital. SUBJECTS: 239 patients with minor disease and long-term vocational absence consecutively admitted to the study. At the one-year evaluation, 17 patients had been readmitted to the team, 7 could not be found, 6 declined the interview and 2 were deceased. At the five-year evaluation of 49 patients who were active after one year, one was deceased and 10 were unable to be found. MAIN OUTCOME MEASURES: Vocational activity. Programme costs. Benefits to society measured by decrease in indirect costs. RESULTS: The one-year vocational rehabilitation rate from the program was 20.5% and the five-year rehabilitation rate was 11.3%. The total discounted cost for case management of the 239 patients was 7.3 MSEK (600,000 Pounds). The decrease in the indirect costs to society from the 28 patients found active after five years was 35.1 MSEK (2,500,000 Pounds). The net present value of the programme at the 1991 price level was 27.5 MSEK (2,365,000 Pounds). CONCLUSIONS: Tertiary care level team-based clinical case management for vocational rehabilitation of patients with chronic minor disease has a positive cost-benefit ratio. A cross-boundary awareness at a health policy level is needed of the societal costs involved for this group of patients who fall between the traditional services in health care and social work.
UNLABELLED: In this study, we assessed the accuracy and reliability of MRI-guided SPECT measurements of medial temporal lobe blood flow in Alzheimer's disease (AD). METHODS: Interactively aligned three-dimensional MP-RAGE MRI and 99mTc-HMPAO SPECT images were used for MRI-guided measurement of medial temporal lobe CBF in eight control subjects and eight patients with probable AD. Intraoperator reliability was assessed by repeated alignment and measurement by one experienced operator. Accuracy was assessed by examining two subjects with fiducial markers. RESULTS: The alignment error was less than 1 SPECT pixel size (3.5 mm) and the coefficient of variation in repeated measures of medial temporal-to-cerebellar CBF ratios was 3.2%. The difference in mean medial temporal-to-cerebellar CBF ratios between eight control subjects and eight AD patients was 12%. Also by using three-dimensional seed-grow defined healthy brain reference regions, there were significant differences between control subjects and AD patients in medial temporal blood flow. Furthermore, the volumes of the MRI-defined medial temporal ROIs were smaller in the AD patients. The best separation between AD patients and control subjects was achieved by combining MRI measurements of atrophy and SPECT measurements of CBF. CONCLUSION: These data show that the accuracy and reliability of MRI-guided SPECT measurements of medial temporal CBF clearly allow the detection of changes in AD. Also, a direct comparison of structural and functional changes is possible by this methodology, which might improve the early diagnosis of AD.
LPS-activated murine peritoneal macrophages produce IL-1 beta but externalize little mature cytokine in the absence of a secondary stimulus, and CTLs previously were reported to serve this capacity. The release of 17-kDa IL-1 beta from LPS-activated BALB/c macrophages occurred rapidly after the addition of C57/B1-derived allogeneic CTLs; within 30 min of coculture, mature IL-1 beta was observed in the medium, and maximum release was achieved within 4 h. CTL-induced post-translational processing was efficient, and >80% of newly synthesized pro-IL-1 beta was released into the medium as the 17-kDa species. Externalization of IL-1 beta required active recognition of the macrophage target by the CTL preparation; C57/B1 CTLs promoted the release of mature IL-1 beta from allogeneic BALB/c macrophages, but not from syngeneic C57/B1 macrophages. In contrast, extracellular ATP promoted mature IL-1 beta release from both macrophage populations. CTL-induced cytokine post-translational processing was blocked by anion transport inhibitors, including 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, UK5099, and the anti-inflammatory agent tenidap. An analogue of tenidap, CP-100,829, was more effective as an inhibitor of both IL-1 beta post-translational processing and anion transport. In contrast, the close structural analogue CP-236,492 inhibited neither process. Tenidap's activity was reversible and was not mimicked by cyclooxygenase inhibitors or by cycloheximide. Therefore, tenidap disrupted CTL-induced IL-1 beta post-translational processing by a mechanism dependent on anion transport inhibition. Multiple stimuli are likely to operate in vivo to promote IL-1 beta post-translational processing, and anion transport inhibitors such as tenidap that suppress cytokine processing independently of the initiating stimulus thus represent attractive candidates as therapeutic regulators of IL-1 production.
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Rotavirus is one of very few viruses that utilizes the endoplasmic reticulum (ER) for maturation. The maturation process is unique not only because it involves translocation of subviral particles across the ER membrane, but also because mature virus is thought to be retained in the ER until cell lysis. Brefeldin A (BFA) is a compound that blocks protein export from the ER to the Golgi complex and causes disruption of the Golgi complex with relocation of resident Golgi proteins to the ER. We found that BFA had a pronounced effect on rotavirus assembly and oligosaccharide processing. Single-step growth experiments demonstrated that BFA reduced infectious progeny rotavirus yield by 99.9%. Immunohistochemical staining with monoclonal antibodies showed that all examined VP4, VP6, VP7, and NS28 epitopes remained unaffected by BFA. A novel observation from pulse-chase experiments was that BFA-treatment rapidly increased the molecular weight of the ER-associated VP7 followed by endo-beta-N-acetylglucosaminidase H (endo H) resistance. A novel observation was also that the trans-ER NS28 protein remained endo H sensitive through the course of BFA-treatment, but that the molecular weight varied during chase. Electron microscopy analysis revealed that BFA interfered in the transition from the intermediate enveloped particle to the mature double-shelled virus.
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Lipid peroxidation of mitochondrial and cell membrane structures is the final step in the oxygen radical-induced damage observed at reperfusion of kidneys after ischaemia. We compared the ability of an indeno-indol compound (code name H290/51) with that of alpha-tocopherol to inhibit lipid peroxidation in reoxygenated isolated rat renal tissue in vitro measured as production of TBARS (thiobarbituric acid reactive substances). H290/51 was 100 times more efficient than alpha-tocopherol. Treatment of rats in vivo with H290/51 in a dosage giving a plasma concentration of 500 nmol L-1 inhibited TBARS production measured in vitro by 80%. Treatment of rabbits with H290/51 almost completely inhibited radical production at reperfusion after 60 min of ischaemia measured with spin trap technique using OXANOH (2-ethyl-3-hydroxy-2,4,4-trimethyloxazolidine) as a spin trap. Furthermore, such pretreatment significantly improved kidney function and survival of rabbits subjected to 60 min of ischaemia to the left kidney and contralateral nephrectomy. These studies stress the importance of inhibiting lipid peroxidation to prevent the ischaemia-reperfusion damage and furthermore suggest a role for treatment with antioxidants like H290/51 in clinical practice, e.g. at reconstructive renal surgery and transplantation.
The purpose of this retrospective study was to examine liver tissue from patients with cholestatic disease for the presence of group C rotavirus RNA. The reverse transcriptase-polymerase chain reaction (PCR) for genes 5 and 6 was used, and the PCR products were subjected to liquid hybridization with a 32P-labeled probe. A second amplification with nested primers was also used. Samples from 32 subjects (20 with biliary atresia or choledochal cyst and 12 controls) were tested. Ten of 20 biliary atresia patients were positive for group C rotavirus RNA; no controls were positive (P < .003). Three of the positive patients were positive for both genes 5 and 6. Six of the 10 had > 1 sample that was positive. These data suggest a possible relationship between group C rotavirus and extrahepatic biliary atresia in the 10 patients in whom virus RNA was detected.
The human Lewis gene encodes an alpha(1,3/1,4)-fucosyltransferase responsible for synthesis of the Le(a) and a Le(b) antigens. To define the molecular background for non-functional Lewis genes we have sequenced PCR-amplified DNA fragments from two Le(a-b-) individuals. One was homozygously mutated at nucleotides 202(T --> C) and 314 (C --> T), altering Trp68 to Arg and Thr105 to Met, and the other was homozygously mutated at nucleotides 59 (T --> G) and 1067 (T --> A), altering Leu20 to Arg and Ile356 to Lys. Using PCR we screened for these and additionally one other mutation at nucleotide 508 (G --> A) among 40 Caucasians. Of 15 Le(a-b-) individuals, 7 typed as le59/1067le202/314, 4 as le202/314le202/314 and 1 as le59/1067le59/1067. Of 21 Le(a-b+) and 4 Le(a+b-), 17 typed as LeLe and 7 as Lele202/314. A pedigree study of 8 Lewis-positive individuals showed that the mutations at nucleotides 202 and 314 were located on the same allele.
Passive immunity against a variety of respiratory and gastrointestinal pathogens has recently been increasingly used clinically, and oral administration of antibodies of both human and non-human origin has been tried both for prophylaxis and treatment of infections. Although the former type of therapy has been shown to be effective, data on the latter are still scarce. This commentary focuses on recent studies on successful oral therapeutic administration of bovine immunoglobulins.
Regional ventilation and perfusion were studied in 10 anesthetized paralyzed supine patients by single-photon emission computerized tomography. Atelectasis was estimated from two transaxial computerized tomography scans. The ventilation-perfusion (V/Q) distribution was also evaluated by multiple inert gas elimination. While the patients were awake, inert gas V/Q ration was normal, and shunt did not exceed 1% in any patient. Computerized tomography showed no atelectasis. During anesthesia, shunt ranged from 0.4 to 12.2. Nine patients displayed atelectasis (0.6-7.2% of the intrathoracic area), and shunt correlated with the atelectasis (r = 0.91, P < 0.001). Shunt was located in dependent lung regions corresponding to the atelectatic area. There was considerable V/Q mismatch, with ventilation mainly of ventral lung regions and perfusion of dorsal regions. Little perfusion was seen in the most ventral parts (zone 1) of caudal (diaphragmatic) lung regions. In summary, shunt during anesthesia is due to atelectasis in dependent lung regions. The V/Q distributions differ from those shown earlier in awake subjects.
PURPOSE: To detect morphological changes in the prostate, as depicted with MR imaging, in order to clarify the effects of transurethral microwave thermotherapy (TUMT). MATERIAL AND METHODS: Twenty patients with prostatism and a prostatic volume of 30-71 cm3 underwent MR examination before, the day after, and 6 months after treatment. TUMT was carried out with a Prostatron. A method to detect oedematous changes on heavily T2-weighted MR images was developed and used as an indicator of morphological changes. RESULTS: The study showed some correlation (r=0.59) between the energy given at TUMT and an increased T2 signal. All patients with increased T2 signal except one were found among those who received the highest amount of energy to the prostate. Of 8 patients, 6 showed a symptomatic response to the treatment and 2 did not. There was a weak statistical correlation (r=0.41) between treatment response and increased T2 signal. CONCLUSION: The study does not support the view that TUMT leads to significant necrosis in the prostate with loss of tissue and retraction. We theorize that the response to TUMT may be caused by a denervation of the prostate.
A previously healthy 3-month-old girl presented with symptoms of meningitis, diarrhoea, vomiting and fever. Green monkey kidney (GMK) cells inoculated with cerebrospinal fluid (CSF) revealed reovirus-like particles by electron microscopy. RNA-gel electrophoresis, immunofluorescence and virus neutralization identified the pathogen isolated from CSF as reovirus type 1. Antibody determination by immunofluorescence of paired sera showed a significant antibody titre rise to the CSF isolate and neutralization test revealed a greater than 4-fold antibody titre rise to the CSF isolate. The CSF isolate was also neutralized by reovirus type 1 antibodies. This report represents one of a few associating reovirus with CNS symptoms in humans.
Decorin and biglycan are structurally related interstitial proteoglycans synthesized in connective tissues like skin, tendon, and cartilage. Despite the conspicuous sequence similarities, where about 55% of the amino acid residues in decorin and biglycan are located in identical positions, the two proteoglycans show differences in their interaction with collagen. Decorin binds to collagen type I, whereas biglycan in several assay systems shows no affinity for this collagen type. Here we have made use of these structural similarities and affinity differences in studies of the collagen binding properties of decorin. Recombinant biglycan/decorin chimeras were produced in mammalian cells and analyzed for their capacity to bind collagen. In the chimeras, biglycan contributes sequences crucial for synthesis and export from the mammalian cells, and decorin provides potential collagen-binding properties. By using this approach we show that decorin binds to the collagen primarily via leucine-rich repeats 4-5 composed of some 40 amino acid residues. Proteoglycan chimeras containing decorin sequences from the N terminus to leucine-rich repeat 3 or sequences from leucine-rich repeat 6 to the C terminus do not show any detectable binding to collagen. A proteoglycan chimera containing decorin leucine-rich repeats 4-5 flanked by biglycan sequences binds to collagen. However, this chimera binds to collagen with somewhat lower affinity than wild type decorin, suggesting that additional low affinity binding sites may be located in other parts of decorin. Alternatively, the conformation of the collagen binding leucine-rich repeats 4-5 are different in decorin and in the biglycan/decorin chimera, leading to a lower collagen affinity for the latter.
A neutralizing monoclonal antibody (1A5) with hemagglutination inhibition activity was produced against a cultivable porcine group C rotavirus strain (strain AmC-1) and used to identify and map the functional topography of the protein involved in viral neutralization. The 1A5 mAb recognized an 82-kDa protein from infected cells as well as an equivalent in vitro-translated protein programmed with gene 3 of the AmC-1 strain. By employing a method called DNA amplification-restricted transcription-translation a series of C-terminal-truncated fragments of the 82-kDa protein was produced. Immunoprecipitation experiments show that 1A5 recognizes an epitope located on vp5, a tentative trypsin cleavage fragment of the 82-kDa protein. The functional and antigenic topography on the 82-kDa protein is discussed in relation to vp4 of group A rotavirus.
The antibody prevalence in Sweden to Norwalk virus (NV) was investigated using a baculovirus expressed capsid antigen. One hundred thirty-two serum samples were examined for IgA, total IgG and IgG subclass antibodies to Norwalk virus. In young children, NV IgG antibody prevalence was higher than the IgA prevalence, whereas no difference was found in individuals older than 21 years. The IgG antibody prevalence was 50% in children below 5 years of age and increased to > 80% in individuals older than 10 years of age. To examine the IgG antibody response in more detail, IgG subclass patterns were characterized. IgG 1 predominated in all age groups. IgG 4, usually detected after repeated exposure to antigen, was the second most prevalent subclass, but was only found in individuals older than 21 years of age. IgG 3 subclass antibodies were found in 13% and IgG 2 in 3% of the sera examined. IgG 3 subclass antibodies have been recognized as a marker for recent or ongoing viral infections.