Alemtuzumab as first-line therapy for B-cell chronic lymphocytic leukemia: long-term follow-up of clinical effects, infectious complications and risk of Richter transformation.
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Adult↗
Biomedical subjects
E Johansson
Publications and source records attributed to E Johansson.
Sequential multidrug chemotherapy (CHOP-VA-MB) in patients with high-grade non-Hodgkin's lymphoma--a 20-year follow-up.
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Adolescent↗
Being victims or beneficiaries? Perspectives on female genital cutting and reinfibulation in Sudan.
Female Genital Mutilation (FGM) or the more value neutral term, Female Genital Cutting (FGC) is widely practised in northern Sudan, where around 90% of women undergo the most extensive form of FGC, infibulation. One new approach to combating FGC in Sudan is to acknowledge the previously hidden form of FGC, reinfibulation (RI) after delivery, when the woman is sewn back so much as to mimic virginity. Based on a qualitative study in Khartoum State, this article explores Sudanese women's and men's perceptions and experiences of FGC with emphasis on RI after delivery. The results showed that both genders blame each other for the continuation of the practices, and the comprehensive understanding of the perceptions and experiences was that both the women and the men in this study were victims of th e consequences of FGC and RI. The female narratives could be understood in the three categories: viewing oneself as being "normal" in having undergone FGC and RI; being caught between different perspectives; and having limited influence on the practices of FGC and RI. The male narratives could be understood in the three categories: suffering from the consequences of FGC and RI, trying to counterbalance the negative sexual effects of FGC and striving in vain to change female traditions. The results indicate that the complexity of the persistence of FGC and RI goes far beyond being explained by subconscious patriarchal and maternalistic actions, related to socially constructed concepts of normality, female identity,tradition and religion a"silent" culture betweenmen and women.
Circumcision, Female↗
IgE-sensitization to predatory mites and respiratory symptoms in Swedish greenhouse workers.
BACKGROUND: Predatory mites are used as biological pesticides worldwide for control of spider mites and other pests in greenhouses. The aim of this study was to evaluate the impact of occupational exposure to Phytoseiulus persimilis and Hypoaspis miles on IgE sensitization among a large group of Swedish greenhouse workers and to examine the relationship between exposure and allergic asthma and rhinoconjunctivitis. METHODS: A total of 96 greenhouse workers from the southern part of Sweden, who were using the predatory mites for control of pests, were investigated with a questionnaire and a medical examination including lung function test. Blood samples were taken to test for allergen-specific IgE antibodies to Phytoseiulus persimilis and Hypoaspis miles as well as to Tetranychus urticae, Dermatophagoides pteronyssinus/farinae and Tyrophagus putrescentiae. RESULTS: Seventeen of the 96 workers were positive in ImmunoCAP to predatory mites: 17 to P. persimilis (17.7%) and 14 to H. miles (14.6%). Subjects sensitized to predatory mites were significantly more often atopic (13/17), defined as a positive Phadiatop, than those who lacked IgE against these mite species (17/79) (P <0.01). IgE antibodies to the red spider mite T. urticae were present among 23 subjects. Thirty-five of the investigated subjects displayed a positive ImmunoCAP to at least one of the investigated mite species. Furthermore, sensitization to any of the mites tested was significantly associated with asthma (OR=9.3) and rhinoconjunctivitis (OR=4.3). CONCLUSIONS: IgE sensitization to predatory mites, P. persimilis and H. miles, is common among greenhouse workers. The findings stress the importance of improved allergen avoidance in greenhouse environments.
Adult↗
Cerebral perfusion assessment by bolus tracking using hyperpolarized 13C.
Cerebral perfusion was assessed with 13C MRI in a rat model after intravenous injections of the 13C-labeled compound bis-1,1-(hydroxymethyl)-1-13C-cyclopropane-D8 in aqueous solutions hyperpolarized by dynamic nuclear polarization (DNP). Since the tracer acted as a direct signal source, several of the problems associated with techniques based on traditional dynamic susceptibility contrast (DSC) MRI contrast agents were avoided. Maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were calculated. The MTT was determined to be 2.8 +/- 0.8 sec. However, arterial partial-volume effects in the animal model prevented accurate absolute quantification of CBF and CBV. It was demonstrated that depolarization of the hyperpolarized 13C tracer via relaxation and the imaging sequence had little influence on CBF assessment when the time resolution of the imaging sequence was short compared to the MTT. However, CBV and MTT were increasingly underestimated as MTT or the depolarization rate increased if depolarization was not taken into account. With a modified bolus-tracking theory depolarization could be compensated for, assuming that the depolarization rate was known. Three separate compensation methods were investigated experimentally and by numerical simulations.
Algorithms↗
Perfusion assessment with bolus differentiation: a technique applicable to hyperpolarized tracers.
A new technique for assessing tissue blood flow using hyperpolarized tracers, based on the fact that the magnetization of a hyperpolarized substance can be destroyed permanently, is described. Assessments of blood flow with this technique are inherently insensitive to arterial delay and dispersion, and allow for quantification of the transit time and dispersion in the arteries that supply the investigated tissue. Renal cortical blood flow was studied in six rabbits using a 13C-labeled compound (2-hydroxyethylacrylate) that was polarized by the parahydrogen-induced polarization (PHIP) technique. The renal cortical blood flow was estimated to be 5.7/5.4 +/- 1.6/1.3 ml/min per milliliter of tissue (mean +/- SD, right/left kidney), and the mean transit time and dispersion in the renal arteries were determined to be 1.47/1.42 +/- 0.07/0.07 s and 1.78/1.93 +/- 0.40/0.42 s2, respectively.
Algorithms↗
Equality or equity in health care access: a qualitative study of doctors' explanations to a longer doctor's delay among female TB patients in Vietnam.
Earlier studies from Vietnam have highlighted the importance of studying gender aspects of health-seeking and diagnosis of potential tuberculosis patients. A longer doctor's delay to diagnosis among female TB patients has been shown. The objective of the present study was to explore doctors' views about and explanations for the longer doctor's delay. Five focus group discussions and three in-depth interviews were performed in a rural province in Vietnam. Thematic content analysis was used to interpret the data. The doctors suggest that women are lost or delayed within the health care-seeking chain, mainly because of barriers associated with the female gender. These barriers are identified, but yet the patient-doctor encounter seems to be steered by an equality principle. This results in gender blindness since equal treatment is suggested despite needs being different. We argue that gender equity should be the guiding principle for the tuberculosis patient-doctor encounter. An equity principle emphasises that needs vary with factors like gender or context. We suggest more research into the health care-seeking chain in order to identify the specific steps where TB diagnosis of men and women may be delayed. Interventions are needed in order to reduce delay to TB diagnosis especially for women and the current TB control strategy, (DOTS), needs to be examined from an equity perspective.
Attitude of Health Personnel↗
Cross-contamination in dishwashers.
Dishwashers are used in central hospital kitchens and ward kitchens to provide clean crockery. Soil recipes based on international standards were tested in order to evaluate the performance of a general dishwasher. In normal use of dishwashers, adherent soils are left on the crockery before cleaning. Different adherent soils, both with and without bacterial contamination, were used to show the effectiveness of the dishwasher to remove this type of soil. It was shown that contamination will occur from the dishwater to crockery with adherent soil. These results demonstrate the importance of cleaning soiled surfaces of crockery mechanically in the dishwashing process. Otherwise cross-contamination, and thereby the spread of infections, may occur.
Cooking and Eating Utensils↗
Interleukin 6, serum amyloid A and haptoglobin as markers of treatment efficacy in pigs experimentally infected with Actinobacillus pleuropneumoniae.
The possibility to use acute phase proteins to monitor the elimination of a bacterial infection in pigs would facilitate an objective assessment of treatment with various antimicrobial substances. To examine this possibility, the acute phase response (IL-6, serum amyloid A (SAA), and haptoglobin) elicited by Actinobacillus pleuropneumoniae and its reduction on treatment with various antibiotics was studied in serum from specific pathogen free (SPF) pigs. Pigs were infected intranasally with A. pleuropneumoniae serotype 2, and either left as non-treated control pigs or treated with different antibiotics intramuscularly at onset of respiratory disease (20h post-infection). Pigs responded to the infection with prominent increases in activity and concentrations of IL-6, SAA, and haptoglobin. These responses were to a certain extent overlapping and covered the time span from a few hours after infection until development of detectable levels of specific antibodies (7-10 days post-infection in untreated pigs). The haptoglobin response lasted until the end of the study on day 17 and thereby partly coincided with the antibody response. Treatment with antimicrobials that effectively reduced establishment of the infection with A. pleuropneumoniae also reduced the duration of all three acute phase responses, and reduced the concentration of serum haptoglobin. In contrast, less efficacious treatments did not reduce these acute phase responses. Thus, acute phase reactants can be applied to monitor therapeutic effects of antimicrobial drugs in the pig and measurements of IL-6, SAA and haptoglobin could add valuable information about the stage of infection during a disease outbreak.
Actinobacillus Infections↗
Characterisation of porcine monocyte-derived dendritic cells according to their cytokine profile.
The influence of interferon (IFN)-alpha on the in vitro differentiation of myeloid porcine dendritic cells (DC) was evaluated as the ability of the DC to stimulate to cell proliferation in a mixed leukocyte reaction (MLR), and as their ability to produce cytokines at exposure to bacterial and viral preparations. Porcine monocytes were enriched from purified peripheral blood mononuclear cells (PBMC) by plastic adherence and cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 or in GM-CSF, IL-4 and IFN-alpha. After 5 days of culture, the cells developed a dendritic morphology and the proportion of cells expressing MHC class II and B7 molecules was increased as determined by flow cytometry. Dendritic cells, differentiated for 5 days in GM-CSF, IL-4 and IFN-alpha, were able to stimulate both allogeneic and syngeneic PBMC to proliferation in an MLR. The DC produced the Th1 associated cytokines IFN-alpha at Sendai virus stimulation, and IL-12 at stimulation with plasmid DNA (pre-incubated in the presence of lipofectin), heat-inactivated Actinobacillus pleuropneumoniae, UV-inactivated Aujeszky's disease virus and live Sendai virus. The heat-inactivated bacteria and Sendai virus also induced production of the Th2 associated cytokines IL-10 and IL-6. The addition of IFN-alpha during differentiation of DC in GM-CSF and IL-4 enhanced their ability to stimulate allogeneic and syngeneic MLR, but did not alter their ability to produce cytokines.
Actinobacillus pleuropneumoniae↗
IgE-mediated sensitization to predatory mites in Swedish greenhouse workers.
BACKGROUND: Predatory mites are used as biological pesticides worldwide for control of spider mites and other pests in greenhouses. The aim of this study was to investigate if predatory and spider mites give rise to sensitization among greenhouse workers who use biological pesticides. METHODS: Blood samples were collected from 31 greenhouse workers from Stockholm area who were using the predatory mites Phytoseiulus persimilis and Hypoaspis miles for control of pesticides. Immunoglobulin E (IgE) binding to extracts of P. persimilis and H. miles and of the spider mite Tetranychus urticae was analysed with sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. RESULTS: A total of 16 workers displayed IgE antibodies to one or more of the three mite species, 32% (n = 10) to P. persimilis, 52% (n = 16) to H. miles and 26% (n = 8) to T. urticae. At least 17 IgE binding components in the molecular weight ranging from 28 to >94 kDa were identified in P. persimilis. In H. miles, at least 11 components were detected, among them at least one major component at about 70 kDa. Twenty-four IgE binding components were found in T. urticae. CONCLUSIONS: In this study we have for the first time shown that the predatory mites P. persimilis and H. miles can cause IgE-mediated sensitization among greenhouse workers. The clinical relevance of sensitization to predatory mites needs to be investigated in further studies.
Adult↗
Patterns of clinical presentation, treatment, and outcome in patients with Waldenstrom's macroglobulinemia: a two-institution study.
Waldenstrom's macroglobulinemia (WM) is in the World Health Organization (WHO) classification considered to be a clinical syndrome rather than a specific pathologic diagnosis. The clinical manifestations associated with WM relate to direct tumor infiltration, hyperviscosity, and deposition of IgM in various tissues. The indications for and choice of treatment vary considerably and no generally accepted prognostic models exist. The clinical features, treatment, and prognosis of 72 patients with WM seen at one British (n = 36) and one Swedish (n = 36) academic center were therefore compared. Significantly more patients presented with a low albumin concentration (< v > 40 g/L, P <.001), anemia (hemoglobin < v > 120 g/L; P <.001), thrombocytopenia (< v > 150 x 10(9)/L; P <.05), hepatomegaly (P <.001), splenomegaly (P <.01), and lymphadenopathy (P <.01), at St Bartholomew's Hospital (SBH) in comparison to the Karolinska Hospital (KH). Fifty-six percent of SBH patients received chemotherapy immediately following diagnosis as compared to 14% at KH. The median overall survival of all patients was 6.3 years; 4.2 years and 11.0 years at SBH and KH, respectively (P <.001). In univariate analysis, anemia (hemoglobin < 120 g/L) and albumin < 35 g/L (but not <40 g/L) at diagnosis predicted a worse overall survival. The presence of hepatomegaly and/or splenomegaly and/or lymphadenopathy was significantly associated with anemia (P <.001) and hypoalbuminaemia (P <.001). The mean Morel score (including age, albumin, and cytopenias) of patients treated at SBH (2.6) was significantly higher than that of KH patients (1.6; P <.001). These findings illustrate the clinical heterogeneity of WM, most probably explained by differences in referral patterns, and in addition, indicate the need for establishing standard criteria for diagnosis, response to treatment, and prognostic features.
Adult↗
Effects of levonorgestrel-releasing intra-uterine system on the expression of vascular endothelial growth factor and adrenomedullin in the endometrium in adenomyosis.
BACKGROUND: The levonorgestrel-releasing intra-uterine system (LNg-IUS) has been used to control menorrhagia, but irregular bleeding during the first 3 months of use was the most notable side effect. Endometrial angiogenesis is believed to be regulated by angiogenic factors. The study aim was to evaluate the effects of LNg-IUS on vascular endothelial growth factor (VEGF) and adrenomedullin (AM) expression in the endometrium. METHODS: VEGF and AM expression were analysed using the avidin-biotin immunoperoxidase method on endometrial curettage specimens from menorrhagic women associated with adenomyosis before and 3 months after LNg-IUS insertion. RESULTS: VEGF expression was abundant both in the endometrial glands and stroma before LNg-IUS insertion, but became scanty 3 months after insertion. No immunostaining for AM was noted in the endometrial glands and stroma before LNg-IUS insertion, whereas AM immunostaining became prominent in the endometrial glands and stroma 3 months after LNg-IUS use. CONCLUSIONS: This is the first study to demonstrate that LNg-IUS insertion results in decreased expression of VEGF and increased expression of AM in the endometrial glands and stroma after 3 months of use. The results obtained suggest that the increase in AM expression in the endometrium may be responsible for the frequent occurrence of irregular bleeding during the initial 3 months of LNg-IUS use.
Adrenomedullin↗
Estradiol/progesterone-releasing vaginal rings for hormone replacement therapy in postmenopausal women.
In order to investigate whether vaginal rings delivering estradiol and progesterone could prevent endometrial hyperplasia and relieve climacteric symptoms, two variants of rings were used in 20 postmenopausal women with intact uteri for 4 months. One ring designated as PI-002 (n = 8) delivered in vitro estradiol 160 microg/day and progesterone 20 mg/day, while the other (PI-003; n = 12) delivered the same dosage of estradiol but only half the progesterone (10 mg/day). Serum estrone, estradiol and progesterone were measured at pretreatment, weekly for 4 weeks, and then monthly for 4 months. The incidence of hot flushes, frequency of night sweats, mood scores, vaginal discharge and bleeding profiles were recorded. Endometrial thickness was monitored by ultrasonography. The mean estrone level was 50 pg/ml for 16 weeks. The mean serum estradiol level was 75 pg/ml for the first 4 weeks and gradually decreased to 50 pg/ml at 16 weeks. The mean progesterone level with the PI-002 ring was 5 ng/ml for the first 4 weeks and decreased to 3.5 ng/ml at 16 weeks. With the PI-003 ring, the mean progesterone level was initially 3.5 ng/ml and then decreased to 2.5 ng/ml thereafter. Significant decreases in the incidence of hot flushes and night sweats as well as a striking improvement in mood scores were noted as early as 2 weeks after insertion. Three of the 20 women discontinued the treatment, owing to ring expulsion. Increased vaginal discharge was observed with both rings in the first 6 weeks. Vaginal bleeding was more frequently apparent among users of the PI-002 ring, although bleeding and spotting were confined to the first 6 weeks. Ultrasonographic monitoring of the endometrium constantly revealed a thickness of < 3 mm for both variants throughout use for 16 weeks. An estradiol/progesterone-releasing vaginal ring is a potential alternative to long-term hormone replacement therapy with minimum attention required. It provides effective protection against endometrial hyperplasia.
Administration, Intravaginal↗
Gradient echo imaging of flowing hyperpolarized nuclei: theory and phantom studies on 129Xe dissolved in ethanol.
The influence of flip angle and flow velocity on the signal intensity achieved when imaging a hyperpolarized substance with a spoiled gradient echo sequence was investigated. The study was performed both theoretically and experimentally using hyperpolarized xenon dissolved in ethanol. Analytical expressions regarding the optimal flip angle with respect to signal and the corresponding signal level are presented and comparisons with thermally polarized substances are made. Both experimentally and theoretically, the optimal flip angle was found to increase with increasing flow velocity. Numerical calculations showed that the velocity dependence of the signal differs between the cases of hyperpolarized and thermally polarized substances.
Echo-Planar Imaging↗
An ELISA for recombinant Lepidoglyphus destructor, Lep d 2, and the monitoring of exposure to dust mite allergens in farming households.
BACKGROUND: Exposure to indoor allergens, such as dust mites, has been recognized as a risk factor for sensitization and symptoms. OBJECTIVE: To develop a two-site ELISA for the determination of Lep d 2 in the reservoir, to measure dust mite allergen exposure (Lep d 2, Der p 1, Der f 1 and Der 2) in farm households, and to investigate whether exposure to these allergens is associated with sensitization, asthma and rhinoconjunctivitis. METHODS: Monoclonal antibodies to recombinant (r)Lep d 2 were produced with standard hybridoma technique. Dust samples from 393 households were analysed for allergen content by two-site ELISA methods. RESULTS: A two-site Lep d 2 ELISA was developed with a detection limit of 0.09 microg/g. The assay was highly reproducible and levels of Lep d 2 showed a strong correlation with the number of Lepidoglyphus mites (r(s): 0.7; P = 0.0002). Lep d 2 was detected in 20% of the homes; levels ranged from 0.09 to 1.7 microg/g of dust. Der p 1 was recorded in 59% of the samples, ranging from 0.055 to 139 microg/g, and Der f 1 and Der 2 in 40% and 50% of the samples, ranging from 0.055 to 24.5 microg/g and 24.3 microg/g, respectively. Dermatophagoides allergens were significantly higher in mattresses than in carpets (P < 0.0001), but this difference was not observed with Lep d 2. A strong relationship between immunoglobulin (Ig)E to rLep d 2 and asthma (OR = 10.4) and rhinoconjunctivitis (OR = 7.5) was seen. Furthermore, sensitization to D. pteronyssinus was significantly associated with asthma (OR: 13.7) and rhinoconjunctivitis (OR: 5.7). CONCLUSION: When assessing mite allergen exposure in rural homes, not only the Der p 1, Der f 1 and Der 2 allergens, but also the Lep d 2 allergen should be taken into consideration.
Agriculture↗
Associations of Fc epsilon R1-beta polymorphisms with immunoglobin E antibody responses to common inhalant allergens in a rural population.
BACKGROUND: Polymorphisms within the beta subunit of the high-affinity receptor for IgE (Fc epsilon R1-beta ) on chromosome 11q13 have been related to atopy and asthma and the lymphotoxin alpha (LT alpha) gene on chromosome 6 is implicated in asthma. OBJECTIVE: To elucidate the association of polymorphisms in the Fc epsilon R1-beta and LT alpha genes to IgE responses and asthma in a family-orientated rural population. METHODS: A total of 461 adult farmers, who participated in an epidemiological follow-up study on respiratory symptoms among farmers on the Swedish island of Gotland, were examined. The traits assessed included serum total IgE, IgE antibody responses to 21 common inhalant allergens and asthma. RESULTS: The 237G mutation was only detected in seven persons. Atopy was found to be associated with the RsaI-ex7 AB-genotype (OR = 1.9; P = 0.04). The RsaI-ex7 B allele had a significant influence on IgE responses to pollens and dust mites (OR = 5.5; P = 0.03 and OR = 5.2; P = 0.049, respectively). The influence of this allele was stronger when the association towards single dust mite species (Lepidoglyphus destructor) was estimated (OR = 7.1, P = 0.03) and the association increased even more when the major allergen of L. destructor (rLep d 2) was analysed (OR = 11.2, P = 0.02). These associations were independent of sex, age and smoking, and the estimates of RsaI-in2 independent of RsaI-ex7. RsaI-in2, RsaI-ex7 and LT alpha genotypes were unassociated with total serum IgE. No significant difference in the distribution of RsaI-in2, RsaI-ex7 and LT alpha genotypes was found among subjects with atopy or asthma compared to healthy controls. CONCLUSION: This study supports the notion that polymorphisms in the Fc epsilon R1-beta gene have significant effects on IgE responsiveness. Secondly, dust mites in rural populations influence the expression of genes on chromosome 11q13.
Adolescent↗
Nasal challenges with recombinant derivatives of the major birch pollen allergen Bet v 1 induce fewer symptoms and lower mediator release than rBet v 1 wild-type in patients with allergic rhinitis.
BACKGROUND: Genetic engineering of the major birch pollen allergen (Bet v 1) has led to the generation of recombinant Bet v 1 derivatives with markedly reduced IgE-binding capacity, but with retained T cell activating ability. OBJECTIVE: To compare the mucosal reactivity to rBet v 1 derivatives with rBet v 1 wild-type as basis for new therapeutic strategies for birch pollen allergy based on mucosal tolerance induction. METHODS: Outside the pollen season, 10 patients with birch pollen allergic rhinitis and mild asthma underwent four nasal challenge-sessions in a randomized, double-blind, and cross-over design, employing increasing doses of rBet v 1 fragment mix, rBet v 1 trimer, rBet v 1 wild-type and diluent (albumin). Nasal lavage fluids (NAL) were collected before the challenge-series as well as 10 min, 4 and 24 h thereafter. Nasal lavage fluid levels of tryptase as well as EPO and ECP were measured as indices of mast cell and eosinophil activity, respectively. RESULTS: All 10 patients tolerated the highest accumulated dose, 8.124 microg, when challenged with rBet v 1 trimer, eight with rBet v 1 fragments compared to one when challenged with rBet v 1 wild-type. No late phase reactions were observed. The change in tryptase levels (pre-challenge vs. 10 min) was significantly lower after challenges with rBet v 1 trimer and rBet v 1 fragments than with rBet v 1 wild-type. The change in EPO/ECP concentration pre-challenge versus 4 h post-challenge was lower for rBet v 1 trimer and the change was significantly lower when pre-challenge versus 24 h post-challenge to rBet v 1 fragments and rBet v 1 wild-type was examined. CONCLUSION: The derivatives induced significantly fewer symptoms and lower mast cell and eosinophil activation than rBet v 1 wild-type upon application to the nasal mucosa. They could in the future be candidates for immunotherapy based on mucosal tolerance induction.
Adult↗