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| 2. |
- Arvanitakis, Alexandros, et al.
(författare)
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Primary prophylaxis implementation and long-term joint outcomes in Swedish haemophilia A patients
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Ingår i: Haemophilia. - 1351-8216.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Primary prophylaxis is the gold standard in severe haemophilia A (SHA) but time to escalate the prophylaxis regimen varies. Aim: Assess prophylaxis implementation and long-term joint health outcomes in SHA with primary prophylaxis. Methods: Adult male patients born after 1980, with SHA on primary prophylaxis, started before the age of 3 years and second joint bleed, and no history of FVIII inhibitors, were enrolled. Repeated joint-health examinations were performed with HJHS or HEAD-US; VERITAS-PRO assessed adherence. Results: Thirty patients were enrolled with, at inclusion, median age 33.5 years, annualized bleed rate and joint bleed rate 0, and FVIII consumption 4232 IU/kg/year, respectively. The median age was 1.2 years, at prophylaxis start once weekly with a median FVIII dose of 47.7 IU/kg, and 1.7 years, by the time escalation to a final regimen had occurred, with a median infusion frequency of thrice weekly and FVIII dose 41.7 IU/kg, respectively. Older age correlated with later transition to escalated prophylaxis (p <.001). Longer time to escalated prophylaxis correlated to more bleeds (p <.001). Median HJHS increased slowly, reaching 4 at 35–40 years. HJHS at 15–20 years correlated with higher HJHS afterwards. Median total HEAD-US score was 1 and correlated with HJHS (p <.001). Median VERITAS-PRO score was 36, indicating good treatment adherence. Conclusion: Primary prophylaxis is effective but does not completely prevent the gradual development of arthropathy in SHA. Joint assessments with HJHS should start at an early age, as they correlate with arthropathy in later life. Prophylaxis escalation should proceed expeditiously to prevent bleeds.
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| 3. |
- Astermark, Jan, et al.
(författare)
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Infrastructural considerations of implementing gene therapy for hemophilia in the Nordic context
- 2023
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Ingår i: Therapeutic advances in hematology. - 2040-6207. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite improvements in hemophilia care, challenges remain, including treatment burden and impaired quality of life. Gene therapy may overcome these. However, its introduction presents a challenge. Objectives: To outline a function-based gene therapy working model describing critical milestones associated with gene therapy handling, administration, and follow-up to facilitate and implement an effective infrastructure for gene therapy introduction. Design: Literature review and consensus discussion among Hemophilia Comprehensive Care centers (HCCCs) in the Nordic region. Methods: Representatives from six HCCCs sought to pinpoint milestones and key stakeholders for site readiness at the pre-, peri-, and post-infusion stages, including authority and genetically modified organism (GMO) product requirements, awareness, medical eligibility, logistics and product handling for infusion, laboratory monitoring, and follow-up. Results: A gene therapy transit map was developed with key stakeholders identified. The approach to prepare the vector will differ between the Nordic centers, but the contracted pharmacy unit will be a key stakeholder. Therefore, a pharmacy checklist for the implementation of gene therapy was developed. For the future, Advanced Therapy Medicinal Product centers will also be implemented. Patients’ expectations, commitments, and concerns need to be addressed repeatedly and education of patients and the expanded health-care professionals team will be the key to successful and optimal clinical management. Eligibility testing according to the product’s summary of product characteristics and frequent follow-up and monitoring post-infusion according to the World Federation of Hemophilia chart will be crucial. Conclusion: The approach to deliver gene therapy in the Nordic region will differ partly between the hemophilia centers, but the defined road map with checklists for the implementation of this advanced therapy will be applicable to all. The map may also serve as a platform for the use of future GMO product options both within and outside the area of hemophilia.
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| 4. |
- Baghaei, Fariba, 1964, et al.
(författare)
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Phenotypic and genotypic characteristics of women in relation to personality traits.
- 2003
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Ingår i: International journal of behavioral medicine. - 1070-5503. ; 10:4, s. 365-78
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Tidskriftsartikel (refereegranskat)abstract
- The associations were examined in women between personality traits and steroid hormones, particularly androgens, as well as polymorphisms in genes regulating androgen concentration and effects. Women, all 42 years of age and premenopausal (n = 270), were recruited randomly. Conventional "masculine" and "feminine" personality traits were examined by questionnaire and set in relation to psychosocial and socioeconomic conditions, behavior in childhood, hormones, risk factors for disease, and polymorphisms in microsatellites in the CYP aromatase and the androgen receptor gene. The proportions of personality traits considered as being dominated by "masculinity" (M) or "femininity" (F) were 44.9%, respectively 15.0%, the rest consisting of a combination of M and F (33.2%) or "undifferentiated" (6.9%). M characteristics were positively associated with education, sporting, self-confidence, and good adaptation to work situation. M scores correlated with reports of "tomboyism" as girls. There was essentially no difference in hormones or disease risk factors between M and F women. The number of (CAG) repeats in the microsatellite of the transactivating domain of the androgen receptor was 19 (2.3; M and SD). M characteristics were more pronounced in the presence of longer repeat stretches (n > 20). No associations were found with F scores. There were no significant associations to the number of tetranucleotide repeats (TTTA) in the fourth introne of the aromatase gene. It was concluded that a majority of women showed M type of personality traits, associated with normal hormones, somatic health, and a long microsatellite in the transactivating domain of the AR gene.
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| 5. |
- Baghaei, Fariba, 1964
(författare)
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Studies of hyperandrogenicity and the metabolic syndrome in premenopausal women
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An androgenic sex hormone profile appears to be a typical feature of the metabolic syndrome (MetS) and a powerful risk factor for the development of type 2 diabetes in women. The causes of relative hyperandrogenicity (HA) are not clearly defined. Among possible pathophysiological pathways, the effect of insulin, abdominal obesity, ovarian dysfunction, environmental factors and disturbed hypothalamic-pituitary-adrenal (HPA) axis activity, as well as genetic factors, have been discussed.The overall aim was to study the associations of endogenous sex hormones and sex hormone-binding globulin (SHBG) with the features of the MetS, HPA axis estimates, ovarian morphology and genetic as well as psychosocial and socioeconomic factors.This thesis is based on a cross-sectional, population-based cohort of premenopausal healthy women born in 1956. The first stage of the investigations was performed in 1997-1998 and comprised 270 subjects. Examinations included assessments of anthropometry, blood pressure, endocrine and metabolic parameters, salivary cortisol levels on repeated occasions over a random working day and a dexamethasone suppression test. Symptoms of anxiety and depression, socioeconomic status and quality of life were determined using validated questionnaires. The influence of sex steroid-related gene polymorphisms (genes encoding androgen receptor (AR), estrogen receptor ¦Á (ER¦Á), estrogen receptor ¦Â (ER¦Â), CYP19 aromatase and SHBG) on sex hormones and SHBG levels was studied. A subgroup of this cohort (n = 55) within the highest and lowest quartiles of free testosterone values were included in a follow-up study in 2001 to perform a detailed gynecological examination, including ovarian sonography.The results revealed that women with HA, defined as the highest 25% levels of free testosterone (free T ¡Ý 6 pmol/L) in this population sample, displayed higher levels of cardiovascular disease (CVD) risk factors, such as fasting insulin, glucose, abdominal obesity, blood pressure, triglycerides and LDL-cholesterol levels, as well as lower HDL-cholesterol, compared with the remaining subjects. Increased adrenal androgen, dehydroepiandrosterone sulfate (DHEAS), appears to be related to some features of the MetS, including dyslipidemia and abdominal obesity. An unfavorable socioeconomic environment and impaired quality of life were associated with an androgenic sex hormone profile. It appears that a chronic challenge to the HPA axis in women due to stress factors may primarily lead to the elevated secretion of the adrenal androgens. Genetic influence may be at least partly responsible for the individual variations in androgen levels and SHBG concentrations. SHBG may play a central role in the regulation of the lipid profile in women, independent of other metabolic and CVD risk factors. There was no clear over-representation of women with polycystic ovaries (PCO) or polycystic ovary syndrome (PCOS). PCO appearance was associated with a tendency towards some non-beneficial changes in cardiovascular risk factors and was correlated with hirsutism. Insulin and free T were independently associated with ovarian volume. The results underline the complexity of HA in women.
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| 6. |
- Baghaei, Fariba, 1964, et al.
(författare)
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The CYP19 gene and associations with androgens and abdominal obesity in premenopausal women.
- 2003
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Ingår i: Obesity research. - : Wiley. - 1071-7323. ; 11:4, s. 578-85
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Elevated androgens in women are associated with type 2 diabetes and are dependent on the conversion to estrogens by aromatase cytochrome P450. Polymorphisms of a tetranucleotide repeat [TTTA](n) in the fourth intron of the CYP19 gene are associated with endocrine-dependent diseases and were examined in relation to hormone levels and disease risk factors in premenopausal women. RESEARCH METHODS AND PROCEDURES: A population sample of women born in 1956 (n = 270) were genotyped for this polymorphism and the results set in relation to steroid hormones, including saliva cortisol, anthropometric variables, estimates of insulin, glucose and lipid metabolism, and blood pressure. RESULTS: Seven tetranucleotide repeat [TTTA](n) alleles were detected with allelic sizes of 168 to 195 bp, with a TCT deletion/insertion (168/171 bp) upstream of this microsatellite. Smoking was associated with elevated androgens (p = 0.005 to 0.019). Using the median (average stretch, 177.5 bp) as a dividing line, nonsmoking women with the shorter microsatellite had higher free testosterone (p = 0.018) and lower sex hormone binding globulin (p = 0.033). These differences were pronounced with the 168-bp allele. Such women were also characterized by a less-substantial decrease of morning cortisols ("unwinding"; p = 0.035) and central obesity (abdominal sagittal diameter, p = 0.049) and had waist/hip circumference ratios of borderline significance (p = 0.064). DISCUSSION: The results indicate that, in premenopausal women, a short microsatellite in the fourth intron of the CYP19 gene, caused by a TCT deletion upstream the [TTTA](n) tract, is associated with elevated androgens, perturbed regulation of the hypothalamic-pituitary-adrenal axis, and abdominal obesity.
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| 7. |
- Baghaei, Fariba, 1964, et al.
(författare)
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The lean woman.
- 2002
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Ingår i: Obesity research. - : Wiley. - 1071-7323. ; 10:2, s. 115-21
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In the current obesity epidemic, the ability to remain lean is beginning to be uncommon. Therefore, it was considered of interest to characterize such subjects. RESEARCH METHODS AND PROCEDURES: From a population of premenopausal women (n = 270), all 40 years of age, those with a similar body mass index (BMI) as women at the age of 21 years, born the same year (BMI = 21.1 kg/m(2)) were selected among nonsmokers and compared with the remaining nonsmoking women. RESULTS: Lean women showed, as expected, low waist-to-hip circumference ratio and abdominal sagittal diameter as well as absence of other disease risk factors. Compared with the remaining women, 17 beta-estradiol was high and androgens were low, whereas insulin-like growth factor I and thyroid hormones showed no differences. Dihydroepiandrosterone sulfate was lower, whereas cortisol, measured in saliva repeatedly over a day, and adrenocorticotropin hormone were not different. Results from questionnaires indicated higher education and socioeconomic status, frequent sports activities, and better psychosocial adaptation and psychological health. A tetranucleotide repeat polymorphism in the fourth [corrected] intron of the aromatase P450 gene was longer among the lean (187 base pairs) than the rest of the women. Women with opposite phylogenetic characteristic have a short microsatellite (168 base pairs) in this gene locus. DISCUSSION: Lean, nonsmoking women enjoy an excellent health in not only anthropometric and metabolic factors, but also in neuroendocrine, endocrine, and psychological variables. The endocrine measurements suggest a well-functioning aromatase, which in turn might have a genetic background, contributing to health. The aromatase gene might be important for regulation of body fat mass.
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| 8. |
- Bah Rösman, Jessica, 1975, et al.
(författare)
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Further exploration of the possible influence of polymorphisms in HTR2C and 5HTT on body weight.
- 2010
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Ingår i: Metabolism. - : Elsevier BV. - 0026-0495. ; 59:8, s. 1156-1163
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Tidskriftsartikel (refereegranskat)abstract
- Receptors of the 5-HT2C subtype are of importance for the influence of serotonin on food intake, and 2 single nucleotide polymorphisms in this gene (HTR2C)-Cys23Ser (rs6318) and -759C>T (rs3813929)-have been reported to be associated with weight and/or antipsychotic-induced weight gain. The present study aimed to replicate these associations; in addition, the 5-HTTLPR polymorphism in the promoter region of the serotonin transporter gene (SLC6A4) was assessed. The polymorphisms were genotyped in subjects recruited from the normal population (n = 510), and possible associations between genotype and body mass index (BMI) were assessed. The Ser23 allele was more common in underweight subjects (BMI <20) than in normal- and overweight (BMI >/=20) subjects (P = .006). The T allele of the -759C/T polymorphism was less common in the overweight group (BMI >/=25) (P = .007). Homozygosity for the short allele of 5-HTTLPR was more frequent in underweight subjects (P = .015). Our results are in agreement with previous studies, suggesting polymorphisms in HTR2C to be associated with body weight, particularly in women; and they also suggest that 5-HTTLPR may influence this phenotype. Further studies on the importance of the investigated genes for eating disorders and drug-induced weight gain are warranted.
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| 9. |
- Bian, Li, et al.
(författare)
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Rutinmässig screening med APTT är inte indicerad före operation : [Routine screening with APTT is not indicated before surgery
- 2022
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Ingår i: Läkartidningen. - : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 119
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Forskningsöversikt (refereegranskat)abstract
- Activated partial thromboplastin time (APTT) is widely practiced in preoperative screening. The value of using this test to predict the risk of perioperative bleeding is not well documented in Sweden. In this article, a literature review is performed to determine whether unselected APTT testing can predict abnormal perioperative bleeding. The current literature does not support coagulation screening with APTT in routine perioperative bleeding assessment, as preoperative screening with APTT has a low sensitivity for detection of clinically significant bleeding disorder. While a comprehensive bleeding history is crucial, the APTT test should only be performed on patients with a history of increased bleeding tendency. The conclusion of this literature review is that patients with a negative bleeding history do not require routine screening with APTT prior to surgery, which, if implemented, would lead to a more cost-effective perioperative routine.
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| 10. |
- Blomqvist, Fredrik Lennart Rune, 1947, et al.
(författare)
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Platelet aggregation in healthy women during normal pregnancy - a longitudinal study.
- 2019
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Ingår i: Platelets. - : Informa UK Limited. - 1369-1635 .- 0953-7104. ; 30:4, s. 438-444
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Tidskriftsartikel (refereegranskat)abstract
- Increased platelet activation is involved in obstetric complications such as preeclampsia and intrauterine growth retardation. It is of interest to study platelet aggregation during pregnancy, since increased aggregation theoretically could be a mechanism associated with placenta-mediated complications, which possibly could be prevented by drugs inhibiting platelet aggregation. There are, however, few robust studies describing platelet aggregation during normal pregnancy. The present longitudinal study was performed in order to study platelet aggregation during normal pregnancy resulting in a healthy child, during the puerperium and in nonpregnant, fertile women. Healthy, nonsmoking, pregnant women (n=104), aged under 39years and with BMI <35, were followed during pregnancy and postpartum. Twenty-seven nonpregnant, non-puerperal, fertile women were studied for comparison. Platelet aggregation was determined with multiple electrode impedance aggregometry and analyzed at inclusion, 4 times during pregnancy and after at least 3 months postpartum. Platelet aggregation postpartum was compared with gestational weeks 8-15 and 37-40, respectively, and with nonpregnant, fertile women. Hemoglobin, leucocyte count, platelet count, prothrombin time, and activated partial thromboplastin time were determined at inclusion in order to verify normal hemostasis. Activation of platelets by arachidonic acid, adenosine diphosphate (ADP), and thrombin receptor activating peptide (trap-6) resulted in less aggregation during pregnancy, compared with postpartum (p<0.03-<0.001). Platelet aggregation following activation by collagen was unchanged. A minor increase in aggregation as pregnancy continued was found related to ADP (p<0.021). Positive correlations were found between platelet counts and platelet aggregation. Postpartum platelet aggregation after activation with arachidonic acid, collagen, and trap-6 was lower than in the non-puerperal fertile state. Other hemostatic analyses were normal. In conclusion, there is a minor decrease in platelet aggregation after activation with arachidonic acid, trap-6, and ADP, measured with multiple electrode impedance aggregometry during normal pregnancy resulting in healthy babies, compared with the postpartum period. The small changes in platelet aggregation may be a consequence of a minor decrease in platelet count and probably lack clinical significance under normal conditions. Interindividual variations at certain time-points are substantial, which limits the usefulness of the multiple electrode impedance aggregometry for determining minor changes in platelet function.
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