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- Bergmann, Olaf, et al.
(författare)
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Cardiomyocyte Renewal in Humans
- 2012
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Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 110:1, s. 17-18
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Druid, Henrik
(författare)
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Experimental acute ischemic renal failure and anticoagulation
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is based on experimental studies on acute renal failure (ARF) in rats. The model employed is that of renal artery clamping, which causes a standardized, ischemic trauma to the kidney. The proximate objective of the investigations was to study iflocal coagulation in the kidney may be induced by a pure ischemic trauma, and whether such a coagulation could be of importance for the development of ARF in this experimental model.The content of isotope-labeled fibrinogen and albumin was determined in postischemic kidneys and controls. After 60rnin of unilateral ischemia, the fibrin(ogen)/degradation products (FIB) and albumin content of the kidney increased rapidly and significantly, approximately averaging 200% of controls. The total kidney weight increased only to 130% of controls. Pretreatment with heparin in a dose of 2000 IU/kg BW, markedly attenuated the increase in kidney weight and content of FIB and albumin.Pretreatment with a lower dose of heparin, 400 IU!kg BW, and warfarin (given intraperitoneally 24 h before the experiment) produced a similar reduction of these parameters, whereas pretreatment with a heparin analog, devoid of anticoagulant effect, did not.In post-ischemic kidneys, scanning electron microscopy (SEM) of cautiously handled freezedried tissue revealed granular and fibrillary material in the tubules and in Bowman's space, at some locations displaying prominent network patterns. Immunofluorescence against FIB showed immunoreactive material in vasa recta, the peritubular capillaries, Bowman's space and in the tubules. By transmission electron microscopy (TEM), fibrin strands lacking periodicity were seen. As compared to controls, the postischemic kidneys generally showed a marked dilatation of Bowman's capsule. No fibrin deposition was seen in heparin pretreated animals.To determine if anticoagulation exerts the described effects by prevention of tubular obstructions or by attenuation of increased glomerular permeability, morphometry of glomeruli was performed by light microscopy and TEM Postischemic kidneys from rats pretreated with saline showed a marked widening of Bowman's space, most likely due to tubular obstruction, whereas Bowman's space width in anticoagulated rats did not differ from controls. Structural changes of the podocyte foot processes as a marker of increased macromolecular permeability were severe in both saline pretreated and anticoagulated kidneys.Glomerular filtration rate fell to 6% of controls after 40 min of ischemia. Warfarin-pretreatment attenuated this decrease significantly. Urinary protein excretion increased in both salinepretreated and anticoagulated rats. The excretion of FIB was significantly increased in warfarinpretreated rats, consistent with the previous observation of an attenuation of FIB content of postischemic kidneys by anticoagulation. This result thus suggests that warfarin did not prevent macromolecular sieving, but reduced the formation of protein-containing tubular casts.In summary, these studies show that a pure ischemic injury to the kidney results in a local coagulation in the kidney, most prominently within Bowman's space and in the tubules. It is suggested that the increased glomerular permeability to macromolecules causes sieving of fibrinogen, which may precipitate in Bowman's space and tubuli and promote the development of tubular obstructions.
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| 5. |
- Eriksson, Anders, et al.
(författare)
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ST-handledarna bör vara vetenskapligt kompetenta
- 2008
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Ingår i: Läkartidningen. - Stockholm : Sveriges läkarförbund. - 0023-7205 .- 1652-7518. ; 105:24-25, s. 1817-1817
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Varför särbehandlas vetenskaplig kompetens negativt jämfört med övriga områden som handledarskap, pedagogik, kommunikation och etik? Frågan ställs i detta inlägg om Socialstyrelsens förslag till föreskrifter och allmänna råd om läkarnas specialiseringstjänstgöring. Författningstexten bör justeras så att handledaren är kompetent inom alla områden, uppmanar artikelförfattarna.
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| 6. |
- Holmgren, Per, et al.
(författare)
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Drug interactions : a challenge in interpreting postmortem toxicology results and a problem in the clinical practice
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective: Multiple drug intake is a problem in tbe clinical setting with potential to adverse drug reactions and certainly a problem in interpretation of forensic toxicology results. The aims of this investigation were to study the incidence of concomitant drugs in autopsy cases where citalopram or zopiclone were detected in femoral blood and to evaluate the potential of drug interactions.Methods: All medico-legal autopsy cases in Sweden during 1992 to 2003 where citalopram or zopiclone were detected in femoral blood at the toxicological analyses were selected. The number and occurrences of concomitant drugs were recorded together with the concentrations as well as the cause of death.Results: In the 2405 cases with citalopram, 123 different drugs, metabolites excluded, were detected 4679 times giving an average of 1.9 concomitant drugs and 1099 different dmg combinations were identified. The corresponding figures for the cases with zopiclone were 1557 cases, 118 different drugs detected 3984 times giving an average of 2.6 concomitant drugs and 977 different combinations. We found a strong positive correlation between the number of drugs detected and the frequency of cases judged to be intoxication.Conclusions: Pharmacokinetic and pharmacodynamic interactions are a potential problem when interpreting forensic toxicological results and the conclusions about the cause and manner of death in the single case must be based on all available information from the investigation and tbe autopsy and on tbe knowledge of tbe pharmacology of included drugs. A better control of prescriptions of what different drugs an individual is given together with a comprehensive therapy control may reduce the risks of adverse drug reactions and unintended or accidental intoxications.
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| 7. |
- Jönsson, Anna K., 1976-
(författare)
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Drug-related morbidity and mortality : Pharmacoepidemiological aspects
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Adverse drug reactions (ADRs) constitute a significant health problem with consequences for the patient as well as for society. Suspected ADRs have been reported to occur in about 2-14% of hospitalised patients. In about 5% of deceased hospitalised patients suspected ADRs may have caused or contributed to the fatal outcome. When a pharmaceutical drug is approved for marketing, the drug has been tested only on a limited number of patients (often <6000) for a limited time period in a controlled environment. Hence mostly common ADRs are detected in these trials. Moreover, certain patient groups, for example patients with co-morbidities, elderly patients, children and pregnant women are often not included in these studies. Thus, it is important to closely monitor the use of drugs after marketing to observe new effects and detect new ADRs.The aim of this thesis is to describe the pattern of pharmaceutical substance use related to morbidity and mortality and to investigate two serious ADRs. We have studied the incidence of fatal ADRs, fatal intoxications, cerebral haemorrhage related to warfarin treatment and venous thromboembolism (VTE) related to treatment with antipsychotic drugs.Observational studies form the basis for this thesis. Data from the Swedish Cause of Death Register, medical case records, the Swedish database on ADRs, the forensic pathology and forensic toxicology databases, and Swedish and Danish hospital discharge registers, Danish prescription registers, and civil registry systems were used.In Paper I we found that 3% of all fatalities in a Swedish population were related to a suspected ADR. Of the deceased hospitalised patients, 6% were related to a suspected ADR. Haemorrhage was the most commonly observed fatal suspected ADR, accounting for almost two-thirds of the events and anticoagulantia was the most common drug group associated with fatal suspected ADRs (almost 50%). A suspected intoxication could have contributed to the fatal outcome in 0.6% of the deceased. Among the fatal intoxications in Swedish medico-legal autopsies studied in Paper II, on average four substances were detected per case. The five most commonly detected substances in individuals with a fatal intoxication were ethanol, propoxyphene, paracetamol, diazepam and flunitrazepam. Among patients diagnosed with cerebral haemorrhage, 10% (59 cases) were treated with warfarin at onset of symptoms (Paper III). Of these, 7 cases (12%) were considered to have been possibly avoidable since the patients were treated with concomitant drugs that have the potential to enhance warfarin effects. The results from Paper IV and Paper V in combination with the published literature suggest that patients treated with antipsychotic drugs have an increased risk for VTE. Compared with non-users, an adjusted odds ratio for VTE of 2.0 was found for users of any antipsychotic drugs in a Danish population. In a medico-legal autopsy series, an adjusted odds ratio for fatal pulmonary embolism of 2.4 and 6.9 was found for users of first-generation low-potency antipsychotics and second-generation antipsychotics, respectively.In summary, drug-related morbidity and mortality is a significant problem and suspected ADRs contribute to a substantial number of deaths. Fatal intoxications are relatively common and it is important to observe changes in patterns of substances associated with fatal intoxications to be able to discover new trends and monitor effects of preventive work. A significant proportion of warfarin-related cerebral haemorrhage was caused by drug-drug interactions and was considered possible to avoid. Users of antipsychotic drugs may increase the risk of VTE.
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| 10. |
- Tjomsland, Vegard, et al.
(författare)
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IL-1α Sustains the Inflammation in Human Pancreatic Cancer Microenvironment by Targeting Cancer Associated Fibroblasts
- 2010
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) is dynamic with an extensive interaction between the stroma and tumor cells. Our aim for this study was to delineate the cross-talk between PDAC and cancer-associated fibroblasts (CAFs) with focus on the mechanism creating the chronic inflammatory tumor milieu. We assessed the effect cross talk between primary PDAC and CAF cell lines propagated from tumors had on the creation and sustenance of an inflammatory environment and what factors that were involved in establishing the inflammation. The coculture of PDAC and CAF cell lines, propagated from tumor tissues, enhanced the levels of inflammatory factors including IL-1α, IL-6, CXCL8, VEGFA, CCL20, and COX-2. The production of these factors correlated with the expression detected in vivo in PDAC tissues. The key producers of nearly all inflammatory factors were the CAFs and not the tumor cells. IL-1α was produced by the tumor cell lines, whereas almost all IL-1RI was expressed by CAFs thus corresponding to their in vivo expression profile in PDAC tissues, indicating a role for the IL-1 signaling cascade in a tumor favorable microenvironment. Neutralization of the IL-1α pathway efficiently diminished the cross talk induced production of inflammatory factors, both in stroma and tumor cells. These data suggest that the cross-talk between PDAC cells and the main stroma cell type, i.e. CAFs, is one contributing factor in the formation of the inflammatory tumor environment and we propose that the neutralization of IL-1α pathway might be a potential therapy for this cancer.
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