Development of specific antibody patterns and clinical symptoms following Ockelbo virus infection

Summary Sixteen patients with symptoms typical for Ockelbo disease (rash, arthralgia, fever) were enrolled in a 2 1/2 year study, during which clinical symptoms were recorded and ELISA was employed to study specific IgM, IgG and IgG subclass development. Initially, all patients presented with rash and arthralgia, and five patients still suffered from joint symptoms at the end of the study period. Ockelbo virus specific IgM was detected during the first week post onset in 6 patients and in 15 patients by day 14. One patient failed to develop specific IgM and was later diagnosed with a human parvovirus B 19 infection. All patients were IgM-negative 2 1/2 years post onset. Seroconversions or significant titer rises for specific total IgG were seen in 15 patients. IgG titers generally peaked within one year but in two patients maximum titers were seen 2 1/2 years post onset. Development of IgG1 followed that of total IgG, while IgG3, after an initial increase in all Ockelbo disease patients, remained at peak levels for one year in four patients, three of whom still had detectable IgG3 at the end of the study period. Ockelbo virus specific IgG2 or IgG4 was not detected in any of the patients.     

Kinetics of Antibody Responses in Rickettsia africae and Rickettsia conorii Infections

African tick-bite fever, caused by Rickettsia africae, is the most common tick-borne rickettsiosis in sub-Saharan Africa. Mediterranean spotted fever due to Rickettsia conorii also occurs in the region but is more prevalent in Mediterranean countries. Using microimmunofluorescence, we compared the development of immunoglobulin G (IgG) and IgM titers in 48 patients with African tick-bite fever and 48 patients with Mediterranean spotted fever. Doxycycline treatment within 7 days from the onset of disease significantly prevented the development of antibodies to R. africae. In patients with African tick-bite fever, the median times to seroconversion with IgG and IgM were 28 and 25 days, respectively, after the onset of symptoms. These were significantly longer by a median of 6 days for IgG and 9 days for IgM than the times for seroconversion in patients with Mediterranean spotted fever (P < 10⁻²). We recommend that sera collected 4 weeks after the onset of signs of patients with suspected African tick-bite fever should be used for the definitive serological diagnosis of R. africae infections.     

Anifrolumab für die Therapie des systemischen Lupus erythematodes

Die Innere Medizin -     

A case of Q fever acquired in Sweden and isolation of the probable ethiological agent, Coxiella burnetii from an indigenous source

Serologically verified indigenous Q fever is described in a 52-y-old male, who presented with persistent fever, muscle and joint pain, headache and non-purulent cough. Institution of doxycycline resulted in prompt recovery. Coxiella burnetii was isolated from mouldy hay in a barn. The strain differs from previously isolated ones in Sweden.     

Moderate varus/valgus malalignment after total knee arthroplasty has little effect on knee function or muscle strength: 91 patients assessed after 1 year

Background and purpose — Postoperative muscle strength and component alignment are important factors affecting functional results after total knee arthroplasty (TKA). We are not aware of any studies that have investigated the relationship between them. We therefore investigated whether coronal malalignment of the mechanical axis and/or of individual implant components would affect knee muscle strength and function 1 year after TKA surgery.Patients and methods — We included 120 consecutive osteoarthritis (OA) patients admitted for TKA. Preoperative active range of motion (ROM) of the knee, patient age, sex, and BMI were recorded and the Knee Society score (KSS) and knee joint extensor/flexor muscle strength were assessed. At 1-year follow-up, the mechanical and coronal component alignment was measured from a postoperative long standing radiograph, and ROM, KSS, and muscle strength measurements were taken in 91 patients. Functional outcome and muscle strength measurements were compared between normally aligned and malaligned TKA groups.Results — 29 of 91 TKAs were malaligned, i.e. they deviated more than 3° from the neutral mechanical axis. 18 femoral components and 15 tibial components were malaligned. Before surgery, the malaligned and normally aligned groups were similar regarding sex distribution, BMI, ROM, KSS, and muscle strength. At the 1-year follow-up, the differences between the groups regarding knee joint function and muscle strength were small, not statistically significant, and barely clinically relevant.Interpretation — Moderate varus/valgus malalignment of the mechanical axis or of individual components has no relevant clinical effect on function or muscle strength 1 year after TKA surgery.Failure to restore limb alignment in total knee arthroplasty (TKA) increases the risk of revision (Jeffery et al. 1991, Ritter et al. 1994 and 2011, Berend et al. 2004), but the effect of accurate postoperative alignment on TKA function is controversial (Lotke and Ecker 1977, Choong et al. 2009, Fang et al. 2009, Longstaff et al. 2009, Huang et al. 2012).Huang et al. (2012) reported that TKAs with a coronal alignment within 3° from the neutral axis had better function and quality of life at 5-year follow-up than TKAs that deviated more than 3° from neutral alignment. Other studies comparing computer-assisted TKA with conventional TKA surgery have not been able to correlate malalignment with inferior functional outcomes (Spencer et al. 2007, Kamat et al. 2009, Kim et al. 2009, Burnett and Barrack 2013).Patients with greater preoperative muscle strength have been reported to have faster recovery and better functional outcome after TKA (Mizner et al. 2005, Yoshida et al. 2008). However, full recovery of muscle strength after TKA is uncommon (Berth et al. 2002, Valtonen et al. 2009, Maffiuletti et al. 2010, Vahtrik et al. 2012).It is plausible that failure to restore the mechanical axis restoration results in inferior muscle function. Sogabe et al. (2009) found different cross-sectional areas in the quadriceps muscles with different knee alignments. They suggested that knees with varus or valgus deformation should have poorer muscle function compared to normally aligned knees. However, we have not been able find any studies investigating muscle strength after TKA in relation to component alignment and mechanical axis restoration.We investigated whether coronal malalignment of the mechanical axis and/or of individual implant components would affect knee muscle strength and function 1 year after TKA surgery.     

Tissue plasminogen activator release in chronic venous hypertension due to heart failure.

In order to study the effects of chronic venous hypertension due to heart failure on blood fibrinolytic activity, tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor 1 (PAI-1) antigen, t-PA activity and PAI activity were measured before and after venous occlusion of the arm for 20 min in 15 patients with right-sided heart failure, 15 patients with left-sided heart failure, and 30 control healthy subjects. Central venous pressure, measured by observing the jugular veins, was above 15 cm of the blood column in all patients with right-sided heart failure, and normal (below 8 cm) in all patients with left-sided heart failure and control subjects. There was no difference in the basal concentrations of t-PA (11.0, 10.2 and 10.8 ng/ml; all values medians) and PAI-1 antigens and their activities between right and left-sided heart failure and the control subjects. After the occlusion, t-PA antigen increased significantly less in right-sided heart failure (28.6 ng/ml) than in left-sided heart failure and the control subjects (54.5 and 45.9 ng/ml, respectively). It was concluded that the poor increase in fibrinolytic activity that had already been reported in patients with heart failure, was due to low t-PA release during occlusion and not to a high basal PAI level. It was limited to the patients with right-sided heart failure and was probably the consequence of chronic systemic venous hypertension.     

Disseminated Cutaneous Rhinosporidiosis

Two cases of longstanding rhinosporidiosis developed widespread asymptomatic nodular skin lesions. Cutaneous examination showed multiple, discrete, sessile and pedunculated, smooth and warty, friable nodular lesions of variable sizes and shapes. Histopathology of representative skin lesions showed hyperplastic epidermis with sporangia containing spores in the upper dermis diagnostic of rhinosporidiosis. Epidemiological data about rhinosporidiosis at Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India, is presented. Possible modes of dissemination to the skin and differential diagnosis are discussed in relation to this rare manifestation of rhinosporidiosis.     

Systemic inflammatory responses in African tick-bite fever

Information regarding the inflammatory response in African tick-bite fever (ATBF), an emerging spotted-fever-group rickettsiosis, in international travelers to sub-Saharan Africa, is scarce. Plasma/serum levels of von Willebrand factor (vWF), soluble (s) E-selectin, tumor necrosis factor-alpha, interleukin (IL)-6, interferon-gamma, IL-10, IL-13, IL-8, RANTES, macrophage inflammatory protein-1alpha, and C-reactive protein were studied, at both first presentation and follow-up, in 15 patients with travel-associated ATBF and in 14 healthy travelers who served as control subjects. Our main and novel findings are the following: (1) patients with ATBF had increased levels of vWF and sE-selectin, with a subsequent decrease at follow-up; (2) with the exception of IFN-gamma, levels of cytokines and chemokines were also increased in these patients at the first presentation; and (3) IL-10 and IL-13 tended to increase during follow-up, whereas most of the inflammatory cytokines decreased. The induction of these mediators and the balance between them may be critical both for the regulation of inflammation and for protective immunity in ATBF.     

Dengue fever in travelers to the tropics, 1998 and 1999

Dengue fever (DF) has become common in western travelers to the tropics. To improve the basis for travel advice, risk factors and dengue manifestations were assessed in 107 Swedish patients for whom DF was diagnosed after return from travel in 1998 and 1999. Patient data were compared with data on a sample of all Swedish travelers to dengue-endemic countries in the same years. Only three of the patients had received pretravel advice concerning DF from their physicians. Hemorrhagic manifestations were common (21 of 74 patients) but caused no deaths. Risk factors for a DF diagnosis were travel to the Malay Peninsula (odds ratio [OR] 4.95; confidence interval [CI] 2.92 to 8.46), age 15-29 years (OR 3.03; CI 1.87 to 4.92), and travel duration >25 days (OR 8.75; CI 4.79 to 16.06). Pretravel advice should be given to all travelers to DF-endemic areas, but young persons traveling to southern and Southeast Asia for >3 weeks (who constituted 31% of the patients in our study) may be more likely to benefit by adhering to it.     

High D-dimer levels predict cardiovascular events in patients with chronic atrial fibrillation during oral anticoagulant therapy

Atrial fibrillation (AF) is associated with hemostatic abnormalities and increased risk of thrombotic cardiovascular events even during oral anticoagulant therapy (OAT). The aim of our study was to evaluate the predictive value of hemostatic markers for the risk of major cardiovascular events during OAT. The study group comprised 113 patients with chronic AF (70.2 +/- 5.4 years old, 60% men), referred for OAT. Established clinical risk factors and levels of prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complexes (TAT), D-dimer, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) antigen and activity, before and during OAT (after 3.9 +/- 0.7 months; INR 2.57 +/- 0.57) were determined. In all patients OAT significantly suppressed levels of F1+2 by 67%,TAT by 30% and D-dimer by 48% (all p <0.001). During an average follow-up of 44 months 22/111 (20%) patients suffered a combined cardiovascular event (stroke, myocardial infarction, peripheral vascular occlusion or vascular death). Patients with cardiovascular events were significantly older, had more frequent heart failure/systolic dysfunction and had significantly increased levels of D-dimer at entry (63 vs 39 ng/mL, p = 0.005) and during OAT (33 vs 18 ng/mL, p = 0.002), and of t-PA antigen at entry (14.3 vs 10.9 ng/mL, p = 0.02) and during OAT (15.0 vs 11.2 ng/mL, p = 0.05) (all values are medians). In multivariate Cox proportional hazard models, heart failure/systolic dysfunction (hazard ratio 2.91; 95% CI 1.17-7.26; p = 0.02), high levels of D-dimer on OAT (top vs. lower two quartiles) (hazard ratio 4.78, 95% CI 1.39-16.41; p = 0.01) and t-PA antigen levels (continuous variable) (hazard ratio 1.09; 95% CI 1.01-1.17; p = 0.02) were significantly associated with combined cardiovascular events. In conclusion, high levels of D-dimer and t-PA antigen during OAT are significant predictors of combined cardiovascular events in AF patients and, on this basis, could be useful additional markers of cardiovascular risk in such patients.