Clinical safety of enamel matrix derivative (EMDOGAIN®) in the treatment of periodontal defects

Abstract The aim of the present clinical trial was to test tolerability during 2 treatments with EMDOGAIN® in a large number of patients. An open, controlled study design in 10 Swedish specialist clinics was chosen, with a test group of 107 patients treated with EMDOGAIN® in connection with periodontal surgery at 2 surgical test sites per patient. The procedures were performed 2 to 6 weeks apart on one-rooted teeth with at least 4 mm deep intraosseous lesions. A control group of 33 patients underwent flap surgery without EMDOGAIN® at I comparable site. In total 214 test and 33 control surgeries were performed. Serum samples were obtained from test patients for analysis of total and specific antibody levels. 10 of the patients had samples taken before and after the first surgery. 56 other samples were taken after one treatment with EMDOGAIN®, and 63 after 2 treatments. None of the samples, not even from allergy-prone patients after 2 treatments, indicated deviations from established baseline ranges. This indicates that the immunogenic potential of EMDOGAIN® is extremely low when applied in conjunction with periodontal surgery. Comparison between the test and control groups demonstrated the same type and frequency of post-surgical experiences, i.e., reactions caused by the surgical procedure itself. Clinical probing and radiographic evaluation was performed at baseline and 8 months postsurgery. About half of the patients (44 test and 21 control) were also evaluated after 3 years. There was a significant difference between the test and control results at 8 months post surgery. and this difference had increased further at the 3 year follow-up. The 2.5–3 mm increase in attachment and bone level after treatment with EMDOGAIN® was of the same magnitude as seen in the studies with split-mouth design aiming for lest of effectiveness of EMDOGAIN®.     

The association between seated immobility and local lower-limb venous coagulability in healthy adult volunteers: a simulation of prolonged travel immobility.

This is the first study to examine the hypothesis that prolonged sitting is associated with procoagulant changes in the local lower-limb venous system. A comparison was made with upper-limb venous changes. Changes in markers of thrombin generation, fibrinolysis, endothelial perturbation and haemoconcentration were analysed as 10 healthy adult male participants sat for 8 h. The change in foot volume was estimated. Subjective venous thromboembolism assessment was undertaken hourly, along with 2-week and 4-week safety follow-up for clinical events.Expected increases in median prothrombin fragments 1 and 2, thrombin-antithrombin complex and D-dimer were not observed in either limb. An increase greater than 45% in the median tissue plasminogen activator and plasminogen activator-1 molar ratio (t-PA/PAI-1), and a decrease greater than 15% in median soluble thrombomodulin were noted in both limbs. Median haematocrit decreased minimally (1%) in the lower limbs, while the foot volume increased by 4%. Subjects experienced vague symptoms after 6 h of sitting, but none developed symptomatic venous thromboembolism. Upper and lower-limb changes in biomarkers did not correlate, except those in t-PA/PAI-1 ratio and plasminogen activator-1. Significant correlation was found between changes in the lower-limb t-PA/PAI-1 ratio and right foot volume.This study originally reveals that even in the lower limbs, prolonged daytime cramped sitting is not associated with significant procoagulant changes in healthy adult male volunteers, and confirms a previous observation that local lower-limb venous changes are not identically reflected in the upper limbs.     

The anterior cruciate ligament does play a role in controlling axial rotation in the knee

This study deals with the influence of peroperative ligament tension on total tibial rotation at different knee flexion angles. Fourteen human cadaver knees with a mean age of 56 years (range 42–84 years) were examined. The cadaver knees were subjected to internal/external (i/e) rotational torque of 6 Nm, at 10, 30, 50, 70 and 90 deg of knee flexion. The mean total i/e rotation with the anterior cruciate ligament (ACL) intact at 10 deg of knee flexion was 30.4 deg and after removing the ACL, 33.1 deg. At 10 and 30 deg of knee flexion, the increase in i/e rotation was significant, while there was no significant difference in mean values at greater knee flexion. Ligament reconstruction with a tension of 5 N at 30 deg of knee flexion using either the over the top or through the femoral condyle reconstructive procedure restored normal tibial rotation. With increased graft tension the knee motion was increasingly restricted at low angles of knee flexion. Our results indicate that the ACL does play a role in limiting axial rotation, and even minor tensioning forces introduced in any of the two ACL reconstructions used produced restricted knee motion.     

Clinical aspects and immune reactions in sarcoidosis*

Introduction: Sarcoidosis is a granulomatous disorder of unknown aetiology, affecting young adults and frequently involving the lungs. Objective: The aim of the present review was to give an overview of the clinical aspects in sarcoidosis. Results: The majority of patients recover, but some develop a chronic disease that may result in fibrosis and respiratory failure. Besides the lungs, peripheral lymph nodes, the skin, the liver and the eyes are commonly affected as well. The genetic background, as well as environmental factors, is of importance for developing sarcoidosis. The incidence varies in different populations, in the Nordic countries approximately with 20/100 000 new patients yearly. Sarcoidosis is diagnosed when clinical and radiological findings are supported by histological evidence in the form of non‐caseating epithelioid cell granulomas, and when other causes of these features are excluded. Patients in need of treatment are usually treated with corticosteroids, topically or as oral steroids. A clinical effect of immunomodulatory drugs blocking tumour necrosis factor (TNF)α has been suggested from several case reports, while two controlled studies showed only minor effects; however, with a tendency to a more pronounced effect on patients with a more severe disease. The immune response in sarcoidosis, with a typical accumulation of CD4+ T‐cells to the lungs, indicate the existence of specific antigens in this disease. Recently, antigens derived from infectious agents such as Mycobacteria and Proprionibacterium acnes have come into focus. Lymphocyte populations with immunoregulatory functions have recently been investigated and seem to be dysfunctional in sarcoidosis, opening the possibility of developing new treatment strategies in this disease. Conclusion: Recent technical developments have provided better tools, enabling detailed and more thorough analyses of the inflammatory process in sarcoidosis. Please cite this paper as: Grunewald J. Clinical aspects and immune reactions in sarcoidosis. The Clinical Respiratory Journal 2007; 1:64–73.     

Assessment of autonomic dysfunction in Parkinson's disease: the SCOPA-AUT.

We developed a questionnaire to assess autonomic symptoms in patients with Parkinson's disease (PD) and evaluated its reliability and validity. Based on the results of a postal survey in 46 PD patients, 21 multiple system atrophy patients, and 8 movement disorders specialists, items were included according to their frequency, burden, and clinical relevance. The questionnaire was evaluated in 140 PD patients and 100 controls, and test-retest reliability was established in a sample of 55 PD patients. The SCOPA-AUT consists of 25 items assessing the following regions: gastrointestinal (7), urinary (6), cardiovascular (3), thermoregulatory (4), pupillomotor (1), and sexual (2 items for men and 2 items for women) dysfunction. Test-retest reliability was good. Autonomic problems increased significantly with increasing disease severity for all autonomic regions, except sexual dysfunction. We conclude that SCOPA-AUT is a reliable and valid questionnaire that evaluates autonomic dysfunction in PD.     

Incidence of cancer in a cohort of magnesium production workers

The results from a cohort study on the incidence of cancer and the mortality in a cohort of 2391 male workers producing magnesium metal are presented. The study population was restricted to employees with more than one year of work experience in the study plant between 1951 and 1974 and the cohort was observed from 1953 to 1984. Altogether 152 new cases of cancer were observed versus 132.6 expected. Six cases of cancer of the lip were found against 2.3 expected, 21 of stomach cancer against 12.8 expected, and 32 of lung cancer against 18.2 expected. A possible causal relation between exposure to factors in the work environment and the development of cancer is discussed.     

Serological investigation of canine encephalitozoonosis in Norway

Encephalitozoon cuniculi, a microsporidian parasite of vertebrates, is considered a health risk to AIDS patients and other immunocompromised human beings. In most hosts, infection with the parasite runs a subclinical course. In some carnivore species, however, clinical disease affecting whole litters arises from intrauterine transmission of the parasite. In both blue foxes (Alopex lagpus) and dogs (Canis familiaris), outbreaks of encephalitozoonosis can be severe. Canine encephalitooonosis has been reported from various parts of the world, including South Africa and the United States. In Norway, there have been large outbreaks of the disease in blue fox farms, affecting also mink, but there have been no reports of encephalitozoonosis in dogs. Infection in dogs would represent a zoonotic problem, due to the close social relationship between dog and man. The purpose of the present study was to investigate the possible occurrence of E. cuniculi infection in Norwegian dogs by serological methods. In the study, 1,104 canine serum samples, originally submitted for biochemical analysis by veterinary practitioners throughout Norway, were screened by enzyme-linked immunosorbent assay for antibodies to E. cuniculi. Samples from 237 of the dogs were tested also by the indirect fluorescent antibody test. All samples were concluded as negative. The results indicate that the likelihood of occurrence of E. cuniculi infection in Norwegian dogs is small.