Eva Holmström

A correlation found between contact allergy to stent material and restenosis of the coronary arteries

Background:  Metallic implants, stents, are increasingly being used especially in patients with stenosis of the cardiac vessels. Ten to thirty per cent of the patients suffer from restenosis regardless of aetiology. We have shown increased frequency of contact allergy to stent metals in stented patients.

High frequency of contact allergy to gold in patients with endovascular coronary stents

Background  Stent implantation is an effective method for treatment of atherosclerotic disease. Factors predisposing to in‐stent restenosis are still largely unknown. Contact allergy to metal ions eluted from the stent has been suggested to be a risk factor.

Knee kinematics and kinetics in former soccer players with a 16-year-old ACL injury – the effects of twelve weeks of knee-specific training

BackgroundTraining of neuromuscular control has become increasingly important and plays a major role in rehabilitation of subjects with an injury to the anterior cruciate ligament (ACL). Little is known, however, of the influence of this training on knee stiffness during loading. Increased knee stiffness occurs as a loading strategy of ACL-injured subjects and is associated with increased joint contact forces. Increased or altered joint loads contribute to the development of osteoarthritis.The aim of the study was to determine if knee stiffness, defined by changes in knee kinetics and kinematics of gait, step activity and cross-over hop could be reduced through a knee-specific 12-week training programme.MethodsA 3-dimensional motion analysis system (VICON) and a force plate (AMTI) were used to calculate knee kinetics and kinematics before and after 12 weeks of knee-specific training in 12 males recruited from a cohort with ACL injury 16 years earlier. Twelve uninjured males matched for age, sex, BMI and activity level served as a reference group. Self-reported patient-relevant data were obtained by the KOOS questionnaire.ResultsThere were no significant changes in knee stiffness during gait and step activity after training. For the cross-over hop, increased peak knee flexion during landing (from 44 to 48 degrees, p = 0.031) and increased internal knee extensor moment (1.28 to 1.55 Nm/kg, p = 0.017) were seen after training, indicating reduced knee stiffness. The KOOS sport and recreation score improved from 70 to 77 (p = 0.005) and was significantly correlated with the changes in knee flexion during landing for the cross-over hop (r = 0.6, p = 0.039).ConclusionKnee-specific training improved lower extremity kinetics and kinematics, indicating reduced knee stiffness during demanding hop activity. Self-reported sport and recreational function correlated positively with the biomechanical changes supporting a clinical importance of the findings. Further studies are needed to confirm these results in women and in other ACL injured populations.

Vaccination responses to capsular polysaccharides of Neisseria meningitidis and Haemophilus influenzae type b in two C2-deficient sisters: alternative pathway-mediated bacterial killing and evidence for a novel type of blocking IgG.

Meningitis caused by Neisseria meningitidis serogroup W-135 was diagnosed in a 14-year-old girl with a history of neonatal septicemia and meningitis caused by group B streptococci type III. C2 deficiency type I was found in the patient and her healthy sister. Both sisters were vaccinated with tetravalent meningococcal vaccine and a conjugate Haemophilus influenzae type b vaccine. Three main points emerged from the analysis. First, vaccination resulted in serum bactericidal responses demonstrating anticapsular antibody-mediated recruitment of the alternative pathway. Second, addition of C2 to prevaccination sera produced bactericidal activity in the absence of anticapsular antibodies, which suggested that the bactericidal action of antibodies to subcapsular antigens detected in the sera might strictly depend on the classical pathway. A third point concerned a previously unrecognized type of blocking activity. Thus, postvaccination sera of the healthy sister contained IgG that inhibited killing of serogroup W-135 in C2-deficient serum, and the deposition of C3 on enzyme-linked immunosorbent assay plates coated with purified W-135 polysaccharide. Our findings suggested blocking to be serogroup-specific and dependent on early classical pathway components. Retained opsonic activity probably supported postvaccination immunity despite blocking of the bactericidal activity. The demonstration of functional vaccination responses with recruitment of alternative pathway-mediated defense should encourage further trial of capsular vaccines in classical pathway deficiency states.

Normal human serum depleted of Clq, factor D and properdin: its use in studies of complement activation

Normal human sera were depleted of Clq, factor D (D) and properdin (P) by a simple and reproducible procedure providing reagents for analysis of complement‐dependent functions. Classical pathway activity was restored with purified Clq, and alternative pathway activity with purified D and P. Since both activation pathways were abolished, antibodies and other components could be removed without loss of complement activity during immunoabsorption procedures. Synergism between the two pathways during haemolysis of rabbit erythrocytes was clearly demonstrated, and was also found on analysis of C3 cleavage in serum incubated with other alternative pathway activators such as zymosan and inulin. Experiments with a Neisseria meningitidis serogroup W‐135 strain isolated from a patient with inherited P deficiency showed that both pathways were capable of supporting antibody‐dependent killing of the bacteria in serum. The alternative pathway was possibly more efficient than the classical pathway in the assay system. In Clq,D,P‐depleted serum with high concentrations of anticapsular IgG antibodies, the addition of D alone resulted in efficient alternative pathway‐mediated killing. The alternative pathway was equally efficient in a Clq,D,P‐depleted serum with low concentrations of anticapsular antibody, but in this case the reaction required both D and P.

Progression of atherosclerosis in middle‐aged men: effects of multifactorial intervention

Persson J, Israelsson B, Stavenow L, Holmström E, Berglund G (Department of Medicine, Lund University Hospital, Malmö, Sweden). Progression of atherosclerosis in middle‐aged men: effects of multifactorial intervention. J Intern Med 1996; 239: 425–33.

Unexpected sensitization routes and general frequency of contact allergies in an elderly stented Swedish population

Contact allergy to stent material has been proposed to be a risk factor for restenosis, after percutaneous transluminal coronary angioplasty (PTCA) and stenting. Information on the general frequency of contact allergy in the elderly population is scarce and knowledge of possible sensitization routes is important to investigate. The aim of this study was to investigate contact allergy to stent materials and other allergens. Here we report our findings on the frequency of contact allergies apart from those from stent material. In this retrospective study, we patch tested an elderly population, treated with PTCA and stented, with our standard series. A dermatitis population served as controls. We found a high frequency of contact allergy in both groups but a greater ‘contact allergy burden’, with generally higher frequencies for contact allergens, in the dermatitis patients as expected. Myroxylon pereirae and caine mix were apart from metals exceptions with statistically significant higher frequencies (P < 0.01) for the stented patients. Contact allergy to nonmetal sensitizers is common in an elderly Swedish stent population although, on the whole, substantially less than in an age and sex‐matched dermatitis population. The findings indicate the importance of the oral mucosa for sensitization. In a general population that has been treated with a special medication/treatment procedure, contact allergies not suspected (such as to M. pereirae and to the metals) might suddenly peak. This underlines the importance of a careful evaluation of new products and routines with regard to contact allergies in the population.

Serum Bactericidal Activity and Induction of Chemiluminescence of Polymorphonuclear Leukocytes: Complement Activation Pathway Requirements in Defense against Neisseria meningitidis

Serum bactericidal activity and chemiluminescence (CL) responses of polymorphonuclear leukocytes (PMNL) to pathogenic Neisseria meningitidis serogroups B and W-135 and to nonpathogenic serogroup 29E were examined with pooled normal human serum depleted of the complement proteins C1q, factor D, properdin and C5. Purified C1q, factor D, properdin and C5 were added alone or in combination. For investigation of serogroup W-135 meningococci, a C1q, factor D and properdin-depleted postvaccination serum with high concentrations of anticapsular antibodies was also used. Serogroup B and W-135 cultured to log phase were resistant to the bactericidal activity of pooled normal human serum but were efficiently killed through the classical pathway alone when the bacteria were cultured to stationary phase. Nonpathogenic serogroup 29E meningococci in log or stationary growth phases were efficiently killed in serum, predominantly through the classical pathway. Serogroup W-135 meningococci grown to log phase were resistant to classical pathway-mediated bactericidal activity in postvaccination serum but were killed on addition of alternative pathway proteins. Stationary phase serogroup W-135 meningococci were killed through both pathways in the postvaccination serum. In the pooled normal human serum CL responses of PMNL were consistently more pronounced with fully reconstituted C1q, factor D, properdin, C5-depleted serum than with serum reconstituted with C1q, factor D and properdin suggesting contribution of actions related to terminal components. In the absence of C1q, serogroup W-135 meningococci in postvaccination serum induced a significant but delayed alternative pathway-mediated CL response. CL responses induced by serum-opsonized meningococci, in contrast to serum bactericidal activity, were not influenced by culture conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Vaccination against encapsulated bacteria in hereditary C2 deficiency results in antibody response and opsonization due to antibody-dependent complement activation.

Hereditary C2 deficiency (C2D) is an important susceptibility factor for invasive infections caused by encapsulated bacteria such as pneumococci and Haemophilus influenzae type b. The infections are mostly seen in childhood indicating that antibody-mediated acquired immunity is affected. C2D persons and healthy controls were vaccinated with ActHIB® and Pneumo23®. Analysis of specific antibodies to pneumococci serotype 6B, 7F, and 23F, and Hib was performed. Post-vaccination IgG antibodies against pneumococci serotype 6B and 23F at a concentration ≥1.0mg/L was found in similar frequency in C2D persons and controls. Post-vaccination sera from C2D persons showed poor complement-mediated opsonization and phagocytosis of pneumococci by granulocytes when depending on classical and lectin pathway activation only, but increased (p=0.007) and equaled that of the normal controls when also alternative pathway activation was allowed due to antibody-dependent C2 bypass activation. In conclusion, the C2D persons benefited from the vaccination and achieve an increased phagocytic capacity.

Influence of prolonged unilateral cervical muscle contraction on head repositioning – Decreased overshoot after a 5-min static muscle contraction task

The ability to reproduce a specified head-on-trunk position can be an indirect test of cervical proprioception. This ability is affected in subjects with neck pain, but it is unclear whether and how much pain or continuous muscle contraction factors contribute to this effect. We studied the influence of a static unilateral neck muscle contraction task (5 min of lateral flexion at 30% of maximal voluntary contraction) on head repositioning ability in 20 subjects (10 women, 10 men; mean age 37 years) with healthy necks. Head repositioning ability was tested in the horizontal plane with 30 degrees target and neutral head position tests; head position was recorded by Zebris((R)), an ultrasound-based motion analyser. Head repositioning ability was analysed for accuracy (mean of signed differences between introduced and reproduced positions) and precision (standard deviation of the differences). Accuracy of head repositioning ability increased significantly after the muscle contraction task, as the normal overshoot was reduced. An average overshoot of 7.1 degrees decreased to 4.6 degrees after the muscle contraction task for the 30 degrees target and from 2.2 degrees to 1.4 degrees for neutral head position. The increased accuracy was most pronounced for movements directed towards the activated side. Hence, prolonged unilateral neck muscle contraction may increase the sensitivity of cervical proprioceptors.