Familial amyloidotic polyneuropathy: long-term follow-up of abdominal fat tissue aspirate in patients with and without liver transplantation.

To estimate the evolution of amyloid in tissue, we studied abdominal fat aspirates of cases with familial amyloidotic polyneuropathy (FAP) longitudinally at regular intervals between 1994 and 2006. In 22 cases (13 carriers and nine patients) not yet transplanted median follow-up was 3.3 years (range 0.4-11.3). We found a significant increase in the amyloid grade of fat tissue from 2+ to 4+ and from 0 to 4+ in two of three subjects with follow-ups of >7 years, after 7 and 11 years, respectively. All other subjects remained negative or did not show a significant change. In 11 liver transplant patients, follow-up with fat aspirate was available with a median duration of 3.1 years (range 1.0-10.1). A comparison was made with cardiac amyloid as judged by the cardiac septum diameter and the serum NT-ProBNP (N-terminal pro-B-type natriuretic peptide) level. No stable increase of amyloid in fat was seen in any patient. A stable decrease of amyloid grade was seen in one patient 5 years after transplantation. In contrast, the cardiac septum diameter increased >or=4 mm in six of the 11 transplant patients. Our study shows the diagnostic utility of a regularly repeated fat aspirate in carriers at risk for the development of ATTR amyloidosis. Evolution of amyloid deposition in fat tissue is very gradual. After liver transplantation, amyloid deposition in fat tissue seems to stabilize and may even decrease in the long term, whereas amyloid deposition in cardiac tissue appears to be progressive.     

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.     

Steady-state fluctuation and variability of betaxolol and atenolol plasma levels

Twenty-four nonsmoking male volunteers took 50 mg atenolol or 10 mg betaxolol orally once a day for 9 days in a two-period, four-sequence, randomized, crossover study. Plasma concentrations reached steady state after day 5. Percent fluctuation in plasma concentration defined as (Cmax-Cmin)/Cavg (% fluctuation 1) was 97% on day 9 for betaxolol and 343% for atenolol; thus atenolol fluctuation was more than threefold that of betaxolol. A 10-fold difference in plasma level fluctuation was observed when fluctuation was defined as (Cmax-Cmin)/Cmin (% fluctuation 2). The intersubject variances for % fluctuation 1 and % fluctuation 2 were 4.1 and 85.5 times greater for atenolol than for betaxolol; these differences were marginally statistically significant for % fluctuation 1 and significant for % fluctuation 2. The intrasubject variabilities for area under the curve and plasma level fluctuations were statistically greater for atenolol than for betaxolol. Atenolol intrasubject variances were 25 and 271 times greater than for betaxolol for % fluctuation 1 and % fluctuation 2, respectively. Thus, betaxolol exhibited less fluctuation in plasma levels with substantially less intersubject and intrasubject variability. These factors would be expected to provide a more consistent therapeutic response and more dependable dosage adjustment.