Infection, immunity and the development of local skin reactions in rabbits infected with cyclically-transmitted stocks ofTrypanosoma congolense

1983 ◽  
Vol 77 (6) ◽  
pp. 569-582 ◽  
Author(s):  
A. G. Luckins ◽  
P. F. Rae ◽  
A. R. Gray
Keyword(s):  
2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 179.1-180
Author(s):  
E. Sag ◽  
F. Akal ◽  
E. Atalay ◽  
U. Kaya Akca ◽  
S. Demir ◽  
...  

Background:FMF is a prototype of autoinflammatory diseases associated with excess IL1 production. Anti-IL1 treatments are the first-line alternatives in colchicine resistant/intolerant FMF patients.Objectives:We aimed to investigate the efficacy and safety of anti-IL1 treatment in pediatric FMF patients in our local (HELIOS) registry.Methods:HELIOS (Hacettepe univErsity eLectronIc research fOrmS) is a web-based biological drug registry for pediatric rheumatology patients (helios.hacettepe.edu.tr). Data were recorded at biological treatment onset (month 0), at month 6 and yearly thereafter in patients. We have analysed the clinical features, disease activity parameters, treatment responses and safety outcomes in FMF patients treated with anti-IL1 agent.Results:Forty pediatric FMF patients were included to the study group (67% female).Thirty-four patients received continous anti-IL1 treatment. The mean age at the start of the colchicine was 5.55±3.87 years. Age at onset of the anti-IL1 treatment was 11.47±5.41 with a mean follow-up duration of 3.87±1.96 years. Apart from two patients, all of them had biallelic exon-10 mutations.We have also given anti-IL1 treatment on an on-demand basis in six adolescent patients. Five of them were having very severe attacks during menstrual periods and one was having attacks during extreme stress periods along with very high CRP levels. The quality of life has markedly improved and these patients no longer reveal any CRP elevation.Anakinra was used as the first-line anti-IL1 treatment. During the last visit, six patients were treated with anakinra and 28 patients were treated with canakinumab. Anti-IL1 treatment decreased the CRP levels, number and severity of the attacks. (Figure 1.) There were three hospitalizations reported due to mild infections. Eleven patients had local skin reactions, two patients had leukopenia with anakinra and one patient had thrombocytopenia with canakinumab. We have discontinued anti-IL1 treatment until the cytopenia subsided. We have switched to on-demand therapy in one patient, started the same treatment and gradually increased the dose in the other two patients. There were no malignancy or other severe adverse reactions.Figure 1.Conclusion:Anakinra and canakinumab are efficient and safe alternatives in colchicine resistant and intolerant pediatric FMF patients. We also for the first time, report on-demand use of anti-IL1 in pediatric FMF patients. We suggest that on-demand treatment should be considered under certain circumstances where the trigger is known and short-lasting (such as menstruation and periods of extreme stress)Acknowledgments:Authors would like to thank Elif Arslanoglu Aydin, Armagan Keskin, Kubra Yuksel and Emil Aliyev for their contribution to the HELIOS registryDisclosure of Interests:Erdal Sag Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Fuat Akal Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Erdal Atalay Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Ummusen Kaya Akca Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Selcan Demir Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Dilara Demirel Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Ezgi Deniz Batu Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Yelda Bilginer Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Seza Özen Consultant of: Novartis, Pfizer, Speakers bureau: SOBI, Novartis


2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Laura Held ◽  
Thomas Kurt Eigentler ◽  
Ulrike Leiter ◽  
Claus Garbe ◽  
Mark-Jürgen Berneburg

Background. The therapy for actinic keratoses includes photodynamic therapy (PDT) and imiquimod 5% cream. The sequential use of both could result in better clinical outcomes.Objectives. To enhance efficacy of therapies while improving tolerability, convenience, and patient adherence with a scheme combining two concomitant or sequential AK treatments.Methods. All patients underwent one session of conventional PDT. Two weeks after, the PDT imiquimod 5% cream was applied to the treatment area once daily for three days per week. One course continued for four weeks followed by a clinical evaluation and decision about further treatment. Patients who had not cleared all of their AK lesions in the treatment area in course 1 participated in a second 4-week course of treatment.Limitations. Small size of population.Results. Three participants were enrolled. Two patients showed complete clinical clearance of AKs. The effect was also noted after long-term followup, at months seven and eleven. No subject discontinued for an adverse event. There were severe local skin reactions in two participants which were severe erythema, scaling, and crusting. One patient showed no response to the therapy.Conclusions. Photodynamic therapy followed by imiquimod was well tolerated and improved reduction of actinic keratoses. This initial proof-of-concept should be studied in larger clinical trials.


2010 ◽  
Vol 1 (3) ◽  
pp. 122-141 ◽  
Author(s):  
Harald Breivik ◽  
Tone Marte Ljosaa ◽  
Kristian Stengaard-Pedersen ◽  
Jan Persson ◽  
Hannu Aro ◽  
...  

AbstractObjectivePatients with osteoarthritis (OA) pain often have insufficient pain relief from non-opioid analgesics. The aim of this trial was to study efficacy and tolerability of a low dose 7-day buprenorphine transdermal delivery system, added to a NSAID or coxib regimen, in opioid-naïve patients with moderate to severe OA pain.MethodsA 6 months randomised, double-blind, parallel-group study at 19 centres in Denmark, Finland, Norway, and Sweden, in which OA patients (>40 years) with at least moderate radiographic OA changes and at least moderate pain in a hip and/or knee while on a NSAID or a coxib were randomised to a 7-day buprenorphine patch (n = 100) or an identical placebo patch (n = 99). The initial patch delivered buprenorphine 5 μg/h. This was titrated to 10 or 20 μg/h, as needed. Rescue analgesic was paracetamol 0.5–4 g daily. Statistical analysis of outcome data was mainly with a general linear model, with treatment as factor, the primary joint of osteoarthritis, baseline scores, and season as covariates.ResultsMost patients had OA-radiographic grade II (moderate) or grade III (severe), only 8 in each group had very severe OA (grade IV). The median buprenorphine dose was 10 μg/h. 31 buprenorphine-treated patients and 2 placebo-treated patients withdrew because of side effects. Lack of effect caused 12 placebo-treated and 7 buprenorphine-treated patients to withdraw. The differences in effects between treatments: Daytime pain on movement, recorded every evening on a 0–10 numeric rating scale decreased significantly more (P = 0.029) in the buprenorphine group. Patients’ Global Impression of Change at the end of the double blind period was significantly improved in the buprenorphine group (P = 0.017). The chosen primary effect outcome measure, the Western Ontario and McMaster Universities (WOMAC) OA Index for Pain (P = 0.061), and secondary outcome measures, the WOMAC OA score for functional abilities (P = 0.055), and the WOMAC total score (P = 0.059) indicated more effects from buprenorphine than placebo, but these differences were not statistically significant. In a post-hoc, subgroup analysis with the 16 patients with radiographic grad IV (very severe) excluded, WOMAC OA Index for Pain was significantly (P = 0.039) reduced by buprenorphine, compared with placebo. WOMAC OA score for stiffness and the amount of rescue medication taken did not differ. Sleep disturbance, quality of sleep, and quality of life improved in both groups. Side effects: Typical opioid side effects caused withdrawal at a median of 11 days before completing the 168 days double blind trial in 1/3 of the buprenorphine group. Mostly mild local skin reactions occurred equally often (1/3) in both groups.ConclusionsAlthough the 24 hours WOMAC OsteoArthritis Index of pain was not statistically significantly superior to placebo, day-time movement-related pain and patients’ global impression of improvement at the end of the 6-months double blind treatment period were significantly better in patients treated with buprenorphine compared with placebo. Opioid side effects caused 1/3 of the buprenorphine-patients to withdraw before the end of the 6-months double blind study period.ImplicationsA low dose 7-days buprenorphine patch at 5–20 μg/h is a possible means of pain relief in about 2/3 of elderly osteoarthritis patients, in whom pain is opioid-sensitive, surgery is not possible, NSAIDs and coxibs are not recommended, and paracetamol in tolerable doses is not effective enough. Vigilant focus on and management of opioid side effects are essential.


2019 ◽  
Vol 15 (4) ◽  
pp. 995-1002 ◽  
Author(s):  
Horace Wong ◽  
Corinne Moss ◽  
Steven M. Moss ◽  
Vibhuti Shah ◽  
Scott A. Halperin ◽  
...  

1998 ◽  
Vol 79 (01) ◽  
pp. 50-53 ◽  
Author(s):  
David Lee ◽  
Gregory Denomme ◽  
Danny Lagrotteria ◽  
John Kelton ◽  
Theodore Warkentin

SummaryTo determine whether factor V Leiden is associated with thrombotic events in patients with heparin-induced thrombocytopenia (HIT), we evaluated 165 patients with serologically confirmed HIT for the presence of factor V Leiden and determined the incidence of venous or arterial thrombosis during the period of HIT. Factor V Leiden was detected in 16 of 165 HIT patients (9.7%). HIT-associated venous thrombosis occurred in 11 of 16 factor V Leiden positive subjects and 94 of 149 factor V Leiden negative subjects (69% vs. 63%; p = 0.79). Arterial thrombosis occurred in 1 of 16 factor V Leiden positive subjects and 21 of 149 factor V Leiden negative subjects (6% vs. 14%; p = 0.70). There was no difference in the incidence of proximal limb DVT, pulmonary embolism, venous limb gangrene, local skin reactions, hemorrhagic adrenal infarction, stroke, or myocardial infarction between the groups. No difference in the severity of venous thrombosis between Leiden positive and negative subjects was detected. Our data suggest that in the acute prothrombotic milieu of HIT, heterozygous factor V Leiden is not an important additional risk factor for thrombosis.


Parasitology ◽  
1979 ◽  
Vol 79 (3) ◽  
pp. 337-347 ◽  
Author(s):  
A. G. Luckins ◽  
A. R. Gray

SUMMARYAntigenic relationships of 4 stocks ofTrypanosoma congolensefrom different parts of Africa were examined by immunofluorescence (IFAT) and neutralization tests. Antisera to each stock were obtained from rabbits infected with trypanosomes transmitted byGlossina morsitans. Trypanosomes for use as antigens were obtained from local skin reactions developing on rabbits infected with 2 of the stocks. Using the IFAT and antisera at end-point dilutions approximately 40% of the trypanosomes fluoresced strongly and a further 30% less intensely with homologous antisera, indicating antigenic heterogeneity among the trypanosomes developing in the skin. Using antisera at low dilutions some samples gave cross-reactions with trypanosomes of heterologous stocks, but at higher dilutions there were no cross-reactions with either of the antigens. The lack of cross-reactions at high antiserum dilutions was interpreted as indicating antigenic differences between the 4 trypanosome stocks. Using neutralization tests only homologous antisera reduced the infectivity of trypanosome suspensions. Overall, these observations indicated that there were at least 3 different strains ofT. congolenseamong the 4 stocks examined.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5124-5124
Author(s):  
Wolfgang Lamm ◽  
Beatrice Schauer ◽  
Sandra Eder ◽  
Christoph Zielinski ◽  
Johannes Drach

Abstract Abstract 5124 Introduction: Novel agents like the proteasome inhibitor bortezomib (Btz) and immunomodulatory agents show activity in multiple myeloma (MM) as well as in primary AL amyloidosis (AL). Btz has emerged as a standard of care in the treatment of patients with MM and AL. The approved dose and schedule of Btz is 1.3mg/m2 administered on days 1, 4, 8, and 11 as an intravenous (i.v.) bolus injection. However, among several side effects, peripheral neuropathy (PN) has a particular negative impact on the quality of life of patients treated with Btz. A recent trial provided evidence for a similar efficacy of Btz administered subcutaneously (s.c.) compared to i.v. administration, but side effects including PN were significantly less frequent with s.c. application of Btz. Here we report our experience regarding efficacy and tolerability of treatment with Btz administered s.c. in patients with MM and AL. Patients and Methods: 19 consecutive patients with MM (n = 17) or histologically proven AL (n = 2) were included in this analysis. For s.c. administration, Btz was prepared at a concentration of 2.5 mg/mL (as opposed to an i.v. concentration of 1.0 mg/mL). All patients received Btz at a dose of 1.3 mg/m2 on days 1, 4, 8, and 11. Btz was used in combination regimens with dexamethasone (n = 9), with thalidomide/dexamethasone prior to autologous transplantation (VDT; n = 6), or with melphalan/prednisolone in elderly patients (VMP; n = 4). Results: Patients (male n=7; female n=12) were at a median age of 64 years (range 38–77), and 11 patients (58%) received the Btz-based regimen with Btz s.c. as their first line treatment. At the time of analysis, a median of 3 cycles bortezomib s.c. (range, 1–5) have been administered. Hematological toxicities were only at Grades 1+2 and included anemia (78%) and thrombocytopenia (33%). Only one patient developed a grade 3 PN, and this patient already had pre-existing PN due to prior i.v. administration of Btz. Other non-hematologic side effects were at grades 1+2 including fatigue (11%) and local skin reactions at the site of s.c. injection, which were self-limited. No notable gastrointestinal toxicity was observed, and therefore we stopped the routine use of i.v. hydration and antiemetics, which were previously administered as concomitant therapy with i.v. Btz. Of 14 MM patients so far evaluable for response, 12 (86%) had a PR or better including 5 patients (36%) achieving a CR. Both patients with AL achieved a very good partial remission (VGPR). More data on efficacy with longer follow-up will be presented at the meeting. Conclusion: Our observations confirm the improved toxicity profile of the s.c. administration of Btz in various standard Btz-based combination regimens. In addition, due to the ease of s.c. administration of Btz, patient management has been markedly facilitated at our centre. Disclosures: No relevant conflicts of interest to declare.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8030-8030 ◽  
Author(s):  
R. E. Hawkins ◽  
A. Dangoor ◽  
U. Keilholz ◽  
D. Schadendorf ◽  
A. Harris ◽  
...  

8030 Background: This trialevaluated the safety, immunogenicity and tumour response of increasing doses of DNA plasmid (DNA.Mel3) and MVA viral vector (MVA.Mel3), containing 7 melanoma epitopes. Methods: 41 HLA-A2 positive stage III/IV melanoma patients with unresectable measurable disease were enrolled. Immunisations were administered three weeks apart with continued MVA.Mel3 boosting in patients with tumour control. Epitope-specific CD8+ T cell responses were evaluated using ex vivo tetramer staining and interferon gamma (IFN-γ) ELISPOT assay. Results: DNA.Mel3 was well tolerated at all doses. Dose-related grade 3 local skin reactions and systemic immune-associated reactions were observed following MVA.Mel3, no reactions led to early study discontinuation. Melan-A tetramer responses were observed in 23/36 (64%) evaluable patients, of which 9/36 showed an IFNγ response to at least one epitope in ELISPOT assay. Seven patients (17%) showed tumour control (PR, MR, or SD >6 months), of which 3/7 patients had associated immune responses, including one with PR > 21 months who underwent extended MVA.Mel3 boosting. Overall median progression free survival was 9 weeks (16 weeks for immune responders). Median overall survival for the intention-to-treat population is 11.7 months with follow up of 16 patients continuing. Conclusions: High dose heterologous PrimeBoost immunisation was safe and stimulated immune responses in >50% of late stage metastatic melanoma patients treated. Tumour control was observed with some evidence of association with immune response. [Table: see text] [Table: see text]


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