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1.
  • Nord, Maria, et al. (författare)
  • Levodopa Pharmacokinetics in Brain after Both Oral and Intravenous Levodopa in One Patient with Advanced Parkinson’s Disease
  • 2017
  • Ingår i: Advances in Parkinsons Disease. - Scientific Research Publishing Inc. - 2169-9712. ; 6:2, s. 52-66
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: One patient received oral levodopa during a study aiming for better understanding of the basal ganglia and of the mechanisms of deep brain stimulation of the subthalamic nucleus (STN DBS) with and without intravenous (IV) levodopa infusion in patients with Parkinson’s disease (PD). The results from oral and IV levodopa treatment are presented.Methods: Five patients with advanced PD were included in the original study. During planned STN DBS surgery microdialysis probes were implanted in the right putamen and in the right and left globus pallidus interna (Gpi). During the study, microdialysis was performed continuously and STN DBS, with and without IV levodopa infusion, was performed according to a specific protocol. After DBS surgery, but before STN DBS was started, one patient received oral levodopa/ benserazide and entacapone tablets out of protocol due to distressing parkinsonism.Results: The levodopa levels increased prompt in the central nervous system after the first PD medication intakes but declined after the last. Immediately the levodopa seemed to be metabolized to dopamine (DA) since the levels of DA correlated well with levodopa concentrations. Left STN DBS seemed to further increase DA levels in left Gpi while right STN DBS seemed to increase DA levels in the right putamen and right Gpi. There was no obvious effect on levodopa levels.Conclusions: The results indicate that PD patients still have capacity to metabolize levodopa to DA despite advanced disease with on-off symptoms and probably pronounced nigral degeneration. STN DBS seems to increase DA levels with a more pronounced effect on ipsilateral structures in striatum.
2.
  • Strömland, Kerstin, 1934-, et al. (författare)
  • Oculo-auriculo-vertebral spectrum: associated anomalies, functional deficits and possible developmental risk factors.
  • 2007
  • Ingår i: American Journal of Medical Genetics. Part A. - 1552-4825. ; 143A:12, s. 1317-1325
  • Tidskriftsartikel (refereegranskat)abstract
    • Swedish patients with the oculo-auriculo-vertebral (OAV) spectrum participated in a prospective multidisciplinary investigation. The aims of the study were to describe their systemic and functional defects, especially autism spectrum disorders, and to search for possible etiologic risk factors. Available medical records were studied and the mothers answered a questionnaire on history of prenatal events. A clinical examination evaluating systemic findings, vision, hearing, speech, oral and swallowing function, and neuropsychiatric function, especially autism, was made. Eighteen patients, (11 males, 7 females) aged 8 months to 17 years with OAV were studied. Most frequent systemic malformations included, ear abnormalities (100%), ocular malformations (72%), vertebral deformities (67%), cerebral anomalies (50%), and congenital heart defects (33%). Functional defects consisted of hearing impairment (83%), visual impairment (28%), both visual and hearing impairment (28%), difficulties in feeding/eating (50%), speech (53%), mental retardation (39%), and severe autistic symptoms (11%). Three children were born following assisted fertilization (two intracytoplasmatic sperm injection, one in vitro fertilization), two mothers reported early bleedings, and six (33%) mothers had smoked during pregnancy.
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3.
  • Nord, Maria, et al. (författare)
  • Is Levodopa Pharmacokinetics in Patients with Parkinson’s Disease Depending on Gastric Emptying?
  • 2017
  • Ingår i: Advances in Parkinsons Disease. - Scientific Research Publishing. - 2169-9712. ; 06:01
  • Tidskriftsartikel (refereegranskat)abstract
    • Levodopa uptake from the gastrointestinal tract in patients with Parkinson’s disease (PD) can be affected by delayed gastric emptying (GE). This might lead to fluctuating levodopa levels resulting in increased motor fluctuations. Continuous dopaminergic stimulation (CDS) improves motor fluctuations and could be a result of smoothening in levodopa uptake. In this study we wanted to study the levodopa pharmacokinetics peripherally in PD patients with motor fluctuations and investigate the relation between levodopa uptake and GE and the effect of CDS. PD patients with wearing off (group 1) and on-off syndrome (group 2) were included. Breath tests were performed to evaluate the half time (T1/2) of GE. Concomitantly 1 tablet of Madopark® was given and the levodopa concentrations in blood and subcutaneous (SC) tissue were analyzed for both groups. Group 2 was then given a 10-d continuous intravenous levodopa treatment and the tests were repeated. Higher levels of levodopa in group 1 compared to group 2 in blood (p = 0.014) were seen. The GE was delayed in both group 1 (p < 0.001) and group 2 (p < 0.05) compared to a reference group with healthy volunteers with T1/2 median values 105 and 78 min vs. 72 min. There was no difference in GE between the two PD groups (p = 0.220) or in group 2 before and after infusion period (p = 0.861). CDS resulted in lower levodopa levels in blood (p < 0.001) and SC tissue (p < 0.01). In conclusion, PD patients in early complication phase have a more favourable levodopa uptake than patients later in disease. We found delayed GE in PD patients with motor fluctuations but no obvious relation between GE and levodopa uptake or GE and PD stage. The effect of CDS indicates no effect of CDS on the mechanisms of GE but on the mechanisms of levodopa uptake.
4.
  • Nilsson, Peter, et al. (författare)
  • The enigma of increased non-cancer mortality after weight loss in healthy men who are overweight or obese.
  • 2002
  • Ingår i: Journal of Internal Medicine. - Wiley-Blackwell Publishing Ltd. - 1365-2796. ; 252:1, s. 70-78
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To study effects on non-cancer mortality of observational weight loss in middle-aged men stratified for body mass index (BMI), taking a wide range of possible confounders into account. Design. Prospective, population based study. Setting. Male population of Malmö, Sweden. Participants. In all 5722 men were screened twice with a mean time interval of 6 years in Malmö, southern Sweden. They were classified according to BMI category at baseline (<21, 22-25, overweight: 26-30, and obesity: 30+ kg m-2) and weight change category until second screening (weight stable men defined as having a baseline BMI ± 0.1 kg m-2 year-1 at follow-up re-screening). Main outcome measures. Non-cancer mortality calculated from national registers during 16 years of follow-up after the second screening. Data from the first year of follow-up were excluded to avoid bias by mortality caused by subclinical disease at re-screening. Results. The relative risk (RR; 95% CI) for non-cancer mortality during follow-up was higher in men with decreasing BMI in all subgroups: RR 2.64 (1.46-4.71, baseline BMI <21 kg m-2), 1.39 (0.98-1.95, baseline BMI 22-25 kg m-2), and 1.71 (1.18-2.47, baseline BMI 26+ kg m-2), using BMI-stable men as reference group. Correspondingly, the non-cancer mortality was also higher in men with increasing BMI, but only in the obese group (baseline BMI 26+ kg m-2) with RR 1.86 (1.31-2.65). In a subanalysis, nonsmoking obese (30+ kg m-2) men with decreased BMI had an increased non-cancer mortality compared with BMI-stable obese men (Fischer's test: P=0.001). The mortality risk for nonsmoking overweight men who increased their BMI compared with BMI-stable men was also significant (P=0.006), but not in corresponding obese men (P=0.094). Conclusions. Weight loss in self-reported healthy but overweight middle-aged men, without serious disease, is associated with an increased non-cancer mortality, which seems even more pronounced in obese, nonsmoking men, as compared with corresponding but weight-stable men. The explanation for these observational findings is still enigmatic but could hypothetically be because of premature ageing effects causing so-called weight loss of involution.
5.
  • Hellström Ängerud, Karin, et al. (författare)
  • Differences in symptoms in relation to myocardial infarction.
  • 2016
  • Konferensbidrag (övrigt vetenskapligt)abstract
    • Background: In myocardial infarction (MI) rapid diagnosis and treatment is crucial for the prognosis. Previous research has found that symptom presentation influence pre hospital delay times but studies about differences in MI symptoms between patients with ST-elevation myocardial infarction (STEMI) and non ST-elevation myocardial infarction (NSTEMI) are sparse and inconclusive. To enhance the understanding of symptom presentation in regard to MI type, we aimed to describe symptoms in relation to MI type and to find predictors of STEMI versus NSTEMI in patients with MI.Methods: Patients with MI (n=694) from the SymTime study were included. SymTime was a multicentre cross-sectional study of symptoms and actions in the prehospital phase of MI and data were collected using a previously validated questionnaire administered to MI patients within 24 h of admission to hospital.Results: Patients with STEMI were younger, more often men and smokers. Patients with NSTEMI were more likely to have a history of hypertension, MI and stroke. Chest pain was the most common symptom in both groups. Pain, discomfort, or pressure located in the jaw or teeth, vertigo/pre-syncope, cold sweat and nausea/vomiting were significantly more frequent in patients with STEMI (Table 1). In a multivariate logistic regression model patients with STEMI were more likely to present with cold sweat (OR 4.13, 95% CI 2.71–6.29) jaw pain (OR 2.14, 95% CI 1.02–4.50), and nausea (OR 2.01, 95% CI 1.20–3.33), and less likely to have a history of stroke (OR 0.35, 95% CI 0.15–0.84), fluctuating symptoms (OR 0.54, 95% CI 0.36–0.83) and anxiety (OR 0.54, 95% CI 0.32–0.92) compared to patients with NSTEMI.Conclusion: Patients with STEMI differed significantly from those with NSTEMI regarding symptom presentation. This knowledge is important for health care personnel to recognize symptoms alarming for STEMI when evaluating patients with MI symptoms.
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6.
  • Venetsanos, Dimitrios (författare)
  • Improving management of STEMI patients treated with primary PCI Pharmacotherapy, renal function estimation and gender perspective
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • This thesis focused on the acute management of patients with ST-segment elevation myocardial infarction (STEMI) in an effort to provide information that may improve outcome. The aim was to evaluate the efficacy and safety of bivalirudin versus unfractionated heparin (UFH) in STEMI patients during primary PCI. Furthermore, to provide pharmacodynamic data of novel ways of ticagrelor administration compared to standard tivcagrelor. Additionally, to identify subgroups of patients, such as women who may derive greater benefit from specific antithrombotic strategies due to their risk/benefit profile. Finally, to evaluate current formulas for estimation of renal function in the acute phase of STEMI.In Paper I, all STEMI patients in Sweden between 2008 and 2014, treated with primary PCI and UFH or bivalirudin were included in our analysis. Of the total population of 23 800 patients, 8 783 (36.9%) were included in the UFH group and 15 017 (63.1%) in the bivalirudin group. Concomitant GPI administration was 68.5% in the UFH arm compared to 3.5% in the bivalirudin arm (p&lt;0.01).The adjusted incidence of 30-day mortality was not significant different between the two groups (UFH vs bivalirudin, adjusted HR 0.94; 95% CI 0.82 -1.07). The adjusted risk for 1-year mortality, 30-day and 1-year stent thrombosis and re-infarction did not differ significantly between the two groups. In contrast, patients treated with UFH had a significantly higher incidence of major in-hospital bleeding (adjusted OR 1.62; 95%CI 1.30 -2.03).In Paper II pharmacodynamic data of chewed or crushed ticagrelor compared to standard ticagrelor loading dose (LD) was assessed in 99 patients with stable angina. Platelet reactivity (PR) was assessed with VerifyNow before, 20 and 60 minutes after LD. High Residual platelet reactivity (HRPR) was defined as &gt; 208 P2Y12 reaction units (PRU). Chewed ticagrelor tablets resulted in significantly lower PRU values compared to crushed or integral tablets at 20 and 60 minutes. Crushed ticagrelor LD resulted in significantly lower PRU values compared to integral tablets at 20 minutes whereas no difference was observed at 60 minutes. At 20 minutes, no patients had HRPR with chewed ticagrelor compared to 68% with integral and 30% with crushed ticagrelor LD (p&lt;0.01).In Paper III we presented a pre-specified gender analysis of the ATLANTIC trial including 1 862 STEMI patients that were randomly assigned to pre-hospital versus in-hospital administration of 180mg ticagrelor. Women were older and had higher TIMI risk score. Women had a 3-fold higher risk for all-cause mortality compared to men (5.7% vs 1.9%, HR 3.13, 95% CI 1.78 – 5.51). However, after adjustment for baseline characteristics, the difference was lesser and no longer significant (HR 1.98, 95% CI 0.97 – 4.04). Female gender was not an independent predictor of risk for bleeding after multivariable adjustments (BARC type 3-5 HR 1.52, 95% CI 0.74-3.09). There was no interaction between gender and efficacy or safety of randomised treatment.In Paper IV, forty patients with PCI- treated STEMI were included between November 2011 and February 2013. We validated the performance of the Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD-IDMS), the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Grubb relative cystatin C (rGCystC) equations for estimation of GFR against measured GFR (mGFR) during the index hospitalisation for STEMI.MDRD-IDMS and CKD-EPI demonstrated a good performance to estimate GFR with accuracy within 30% (P30) 82.5% vs 82.5%, respectively. CKD was best classified by CKD-EPI (Kappa 0.83). CG showed the worst performance with the lowest P30. The rG-CystC equation had a marked bias of -17.8% and significantly underestimated mGFR (p=0.03).Conclusions – In STEMI patients treated with primary PCI, bivalirudin should be preferred in patient at high risk for bleeding. With crushed or chewed ticagrelor tablets a more rapid platelet inhibition may be achieved, compared with standard integral tablets. In STEMI patients, fast and potent platelet inhibition with chewed ticagrelor may reduce the risk of early stent thrombosis and patients treated with a less aggressive antithrombotic strategy, such as UFH or bivalirudin monotherapy, may derive a greater benefit. Although gender differences in adverse outcomes could mainly be explained by older age and clustering of comorbidities in women, a bleedreduction strategy in women with high risk characteristics is warranted in order to improve their outcome. Regardless the choice of antithrombotic strategy, dose adjustment of drugs cleared by kidneys based on GFR estimation is of crucial importance. MDRD and CKD-EPI should be the formulas used for estimation of GFR in STEMI patients
7.
  • Wirestam, Lina, 1986-, et al. (författare)
  • Osteopontin is associated with disease severity and antiphospholipid syndrome in well characterised Swedish cases of SLE
  • 2017
  • Ingår i: Lupus Science and Medicine. - BMJ Publishing Group Ltd. - 2053-8790. ; 4:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective The variety of disease phenotypes among patients with SLE challenges the identification of new biomarkers reflecting disease activity and/or organ damage. Osteopontin (OPN) is an extracellular matrix protein with immunomodulating properties. Although raised levels have been reported, the pathogenic implications and clinical utility of OPN as a biomarker in SLE are far from clear. Thus, the aim of this study was to characterise OPN in SLE.Methods Sera from 240 well-characterised adult SLE cases classified according to the American College of Rheumatology (ACR) and/or the Systemic Lupus International Collaborating Clinics (SLICC) criteria, and 240 population-based controls were immunoassayed for OPN. The SLE Disease Activity Index 2000 (SLEDAI-2K) was used to evaluate disease activity and the SLICC/ACR Damage Index (SDI) to detect damage accrual.Results Serum OPN levels were in average raised fourfold in SLE cases compared with the controls (p&lt;0.0001). OPN correlated with SLEDAI-2K, especially in patients with a disease duration of &lt;12 months (r=0.666, p=0.028). OPN was highly associated with SDI (p&lt;0.0001), especially in the renal (p&lt;0.0001), cardiovascular (p&lt;0.0001) and malignancy (p=0.012) domains. Finally, OPN associated with coherent antiphospholipid syndrome (APS; p=0.009), and both clinical and laboratory criteria of APS had significant positive impact on OPN levels.Conclusions In this cross-sectional study, circulating OPN correlates with disease activity in recent-onset SLE, reflects global organ damage and associates with APS. Longitudinal studies to dissect whether serum OPN also precedes and predicts future organ damage are most warranted.
8.
  • Lundberg, Peter, et al. (författare)
  • Kvantifiering av leversteatos: diagnostisk utvärdering av protonmagnetresonansspektroskopi jämfört med histologiska metoder
  • 2016
  • Konferensbidrag (refereegranskat)abstract
    • BakgrundLeversteatos är den vanligaste manifestationen av leversjukdom i västvärlden. Leverbiopsi med semikvantitativ histologisk gradering är referensmetod vid gradering av leversteatos. Med protonmagnetsresonansspektroskopi (1H-MRS), en metod som föreslagits ersätta leverbiopsi för värdering av steatos, kan leverns innehåll av triglycerider mätas icke-invasivt. Triglyceridinnehåll &gt;5,00 % används ofta som ett diagnostiskt kriterium för leversteatos vid undersökning med 1H-MRS. Syftet med studien var att jämföra 1H-MRS med semikvantitativ histologisk steatosgradering och kvantitativ histologisk steatosmätning.MetodPatienter remitterade för utredning av förhöjda leverenzymer in-kluderades i studien. Samtliga patienter genomgick klinisk undersökning, laboratorieprovtagning samt 1H-MRS direkt följd av leverbiopsi. För konventionell histologisk semikvantitativ gradering av steatos användes kriterierna utarbetade av Brunt och medarbetare. Kvantitativ mätning av fett i biopsierna utfördes genom att med hjälp av stereologisk punkträkning (SPC) mäta andelen av ytan som innehöll fettvakuoler.ResultatI studien inkluderades 94 patienter, varav 37 hade icke-alkoholor-sakad fettleversjukdom (NAFLD), 49 hade andra leversjukdomar och 8 hade normal leverbiopsi. En stark korrelation noterades mel-lan 1H-MRS och SPC (r=0,92, p&lt;0,0001; к=0.82). Korrelationen mellan 1H-MRS och Brunts kriterier (к=0.26) samt mellan SPC och Brunts kriterier (к=0.38) var betydligt sämre. När patologens gradering (Brunts kriterier) användes som referensmetod för diag-nos av leversteatos så hade alla patienter med triglyceridinnehåll &gt;5,00 % mätt med 1H-MRS steatos (specificitet 100 %). Emellertid hade 22 av 69 patienter med triglyceridinnehåll ≤5,00 % också le-versteatos enligt Brunts kriterier (sensitivitet 53 %). Motsvarande siffror när man använde gränsvärdet 3,02 % var sensitivitet 79 % och specificitet 100 %. Vid ytterligare reduktion av gränsvärdet för triglyceridinnehåll till 2,00 % ökade sensitiviteten till 87 % med upprätthållande av hög specificitet (94 %).Slutsats1H-MRS och SPC uppvisade en mycket hög korrelation vid kvantifiering av leversteatos. SPC borde därför föredras framför Brunts kriterier när noggrann histologisk kvantifiering av leversteatos är önskvärd. Många patienter kan ha histologisk leversteatos trots triglyceridinnehåll ≤5,00 % mätt med 1H-MRS. Gränsvärdet för diagnostisering av leversteatos med 1H-MRS bör därför reduceras.
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9.
  • Borg, Henrik, et al. (författare)
  • High levels of antigen-specific islet antibodies predict future beta-cell failure in patients with onset of diabetes in adult age
  • 2001
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - The Endocrine Society. - 1945-7197. ; 86:7, s. 3032-3038
  • Tidskriftsartikel (refereegranskat)abstract
    • It is unclear whether high levels of antigen-specific islet antibodies [GADA (glutamic acid decarboxylase 65 antibodies) and IA2-ab (protein tyrosine phosphatase-like protein antibodies)] predict beta-cell failure in patients with onset of diabetes in adult age. Therefore, GADA and IA2-ab levels at the diagnosis of diabetes were related to fasting plasma C-peptide levels 5 yr later in 148 patients with diabetes onset in adult age (age at onset, 20-77 yr; median, 57 yr). Classical islet cell antibodies (ICA) were also determined. Complete beta-cell failure (undetectable fasting plasma C-peptide) was only present in 4 patients at diagnosis of diabetes, but in 21 patients 5 yr thereafter. At diagnosis, ICA were detected in 20 of 21 (95%) patients with beta-cell failure after 5 yr and in only 7 of 127 (5%) without, whereas GADA and/or IA2-ab (>97.5 percentile of healthy controls) were detected in all 21 (100%) with but also in 23 of 127 (18%) patients without beta-cell failure after 5 yr. Thus, ICA had a higher positive predictive value (74%) than GADA and/or IA2-ab (47%; P < 0.05). With high cutoff values for GADA and IA2-ab, however, GADA and/or IA2-ab were detected in 19 of 21 (90%) patients with beta-cell failure vs. only in 5 of 127 (4%) without, giving a positive predictive value of 79%. Slightly elevated GADA levels in IA2-ab-negative patients were associated with progressive but not complete beta-cell failure within the study period. Hence, high GADA and/or IA2-ab levels predict a future complete beta-cell failure, whereas low GADA levels predict slowly progressive beta-cell insufficiency.
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10.
  • Berntorp, Erik, et al. (författare)
  • Centraliserad vård grundläggande i vårdprogram för blödarsjuka
  • 1999
  • Ingår i: Läkartidningen. - Swedish Medical Association. - 0023-7205. ; 96:15, s. 1849-1852
  • Tidskriftsartikel (refereegranskat)abstract
    • Haemophilia is a rare and potentially life-threatening disease. In Sweden, with a population of approximately 8.5 million, about 350 people suffer from the more severe forms of haemophilia or von Willebrand disease. Meticulous management is important if the patients are to be spared chronic disability and serious treatment complications. The disease is lifelong and affects psychosocial aspects of life among patients and their families. With the help of a grant from the Swedish Board of Halth and Welfare, a care programme has been designed to guarantee Swedish haemophiliacs comparable and optimal care. The programme has been drawn up by representatives of the three haemophilia centres in Sweden (at University Hospital, Malmo, Sahlgrenska University Hospital, Gothenburg, and Karolinska Hospital, Stockholm) in co-operation with the World Federation of National Haemophilia Organisations. To ensure optimal individual application of the programme, individualised management strategies and patient information leaflets have been prepared.
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