[Systemic sclerosis-clinical picture, diagnosis, and treatment]. / Systemische Sklerose ­ klinisches Bild, Diagnostik und Therapie.

Systemic sclerosis is a rare rheumatologic disease that is characterised by skin and organ fibrosis as well as vascular changes and the occurrence of specific autoantibodies. It has a high morbidity and mortality while its manifestations show significant heterogeneity in patients. Thus, diagnosis and follow-up of patients with systemic sclerosis has to be extensive, the more so because treatment must be adapted to organ manifestations. Although specific therapies for gastrointestinal, pulmonary or vascular complications exist, patients respond only partly to these and new therapeutic approaches are still needed.

[Systemic sclerosis-clinical picture, diagnosis, and treatment]. / Systemische Sklerose ­ klinisches Bild, Diagnostik und Therapie.

Systemic sclerosis is a rare rheumatologic disease that is characterised by skin and organ fibrosis as well as vascular changes and the occurrence of specific autoantibodies. It has a high morbidity and mortality while its manifestations show significant heterogeneity in patients. Thus, diagnosis and follow-up of patients with systemic sclerosis has to be extensive, the more so because treatment must adapted to organ manifestations. Although specific therapies for gastrointestinal, pulmonary or vascular complications exist, patients respond only partly to these and new therapeutic approaches are still needed.

[Systemic sclerosis : What is currently available for treatment?] / Systemische Sklerose : Was ist gesichert in der Therapie?

Systemic sclerosis (scleroderma) is a rheumatologic disease characterised not only by inflammation/autoimmunity, but also by tissue fibrosis and vascular lesions. The therapeutic approach to patients is dictated by the organ involvement and includes treatment of vascular and fibrotic disease features beyond mere immunosuppression. Fibrotic features in particular, are still inadequately treated, whereas many drugs have been tested for vascular complications within recent years. In this review, the currently available treatment options for this rare disease are presented. Therapy options in systemic sclerosis have changed over the past 10 years and this trend will also continue in the future.

Nailfold capillaroscopy in juvenile rheumatic diseases: known measures, patterns and indications.

Nailfold capillaroscopy has become an established method in adults for the evaluation of structural abnormalities of the microcirculation associated with rheumatic disease. It is a cornerstone for the diagnostic work-up of patients with Raynaud's phenomenon and the early diagnosis of systemic sclerosis. However, this non-invasive examination may also be valuable in children and adolescents with rheumatic diseases. Based on the scarce data available, this review focuses on capillaroscopic findings in healthy children and adolescents as well as in children with juvenile systemic sclerosis, juvenile dermatomyositis, juvenile idiopathic arthritis, and Raynaud's phenomenon. In addition, it outlines the potential benefits and limitations of nailfold capillaroscopy for routine care in paediatric rheumatology.

[Critical limb ischemia in systemic sclerosis]. / Kritische Extremitätenischämie bei systemischer Sklerose.

Vascular complications are common in systemic sclerosis (SSc). Critical limb ischemia leading to gangrene or amputation occurs in more than 10% of these patients and hence is a common emergency. This report highlights the different pathogenetic mechanisms leading to critical ischemic events and provides guidance for the diagnosis and therapy. Apart from SSc-associated vasculopathy and peripheral arterial disease, thromboembolic events and rarely also vasculitis may cause critical limb ischemia. An interdisciplinary approach to the diagnosis and therapy of these lesions is mandatory. Therapy goals are the prevention of further ischemia and, if possible, revascularization as well as optimal pain management.

[Towards an implementation of guidelines for the therapy of systemic sclerosis (scleroderma): between desire and reality]. / Implementation von Leitlinien für eine Therapie der systemischen Sklerose (Sklerodermie) : Wunsch und Wirklichkeit.

The clinical manifestations of systemic sclerosis (scleroderma, SSc) are characterized by three prominent features: autoimmunity/inflammation, vascular lesions (vasculopathy) and (organ) fibrosis. Drugs and other therapies are now available for each of these features. However, due to the low prevalence and high variation in clinical signs and symptoms of the disease, there are only few high quality clinical trials. The EULAR Scleroderma Trials and Research Group (EUSTAR, a subgroup of the European League Against Rheumatism, EULAR) has therefore started to assess the therapies available today and make recommendations. The present article discusses treatment options in systemic sclerosis beyond these recommendations. It is to be expected that the establishment of national and international networks for systemic sclerosis research (e.g. the German Network for Systemic Sclerosis, DNSS, and EUSTAR) will raise the standards of evidence-based therapy for systemic sclerosis in the future by analyzing large data sets and performing clinical trials.

Comparison of operative reconstruction and percutaneous balloon dilatation for central venous obstruction.

To evaluate the efficacy of venous reconstruction versus percutaneous transluminal angioplasty for the treatment of obstruction of the superior vena cava and its major tributaries, we retrospectively reviewed the clinical course of 27 patients, of whom 13 underwent operative reconstruction and 15 had angioplasty (1 had both). Three patients had obstruction of the superior vena cava, 8 had occlusion of the innominate veins, and 16 had obstruction of the subclavian or axillary veins. In both treatment groups, mean age, indications, etiology, and location of the lesion were comparable. No major surgical complications occurred; one patient who underwent angioplasty experienced stent migration to the pulmonary artery without sequelae. Primary symptomatic relief at 1 year was achieved in 88% in the surgical group versus 36% in the angioplasty group (p < 0.05 by Fisher's exact test) and at 2 years in 71% versus 0%, respectively (p < 0.01). One- and 2-year success rates with repeated angioplasty, however, were 86% and 66% (p > 0.9), respectively. We conclude that the long-term success rate of operative reconstruction exceeds that of single percutaneous transluminal angioplasty. However, with repeated angioplasty, success rates approach those of operative reconstruction.

Ischemia-reperfusion injury of the spinal cord: the influence of normovolemic hemodilution and gradual reperfusion.

Recent studies have suggested that oxygen-derived free radicals play an important role in ischemia-reperfusion injury of the spinal cord. In other organ systems, reperfusion injury has been reduced by limiting the availability of oxygen in the reperfusion phase. The purpose of this study was to test the effect of normovolemic hemodilution and gradual reperfusion on spinal cord function after aortic cross-clamping in 84 New Zealand White rabbits. All animals underwent 21 min of infrarenal aortic cross-clamping in the conscious state by means of a previously placed aortic occlusion device and were randomized to four groups. Group 1 animals were hemodiluted to a mean (s.e.m.) hematocrit of 28(2)% by extracting 25% of the effective blood volume and reinfusing the plasma component after centrifugation concurrently with a volume of normal saline three times that of the discarded red cells. Group 2 animals (controls) were bled similarly but both plasma and red cells were reinfused, resulting in a mean (s.e.m.) hematocrit of 38(2)%. In the next two groups, distal aortic flow was recorded via an implantable Doppler device. After cross-clamping, flow was returned gradually over 45 min in animals of group 3, and abruptly in group 4. Animals were observed for 5 days and neurologic function was graded by an independent observer. Paraplegia at 5 h after clamping occurred in 75% of animals in group 1 versus 32% in group 2 (P < 0.05), and in 33% of group 3 versus 28% in group 4 (not significant). Of those animals showing initial neurologic recovery, delayed-onset paraplegia was seen in 100% in group 1 versus 87% in group 4 (not significant), and in 50% of group 3 versus 92% of group 4 (P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Protecting the ischemic spinal cord during aortic clamping: the influence of selective hypothermia and spinal cord perfusion pressure.

PURPOSE: We verified the hypothesis that selective deep hypothermia of the spinal cord during double thoracic aortic clamping can prevent postoperative paraplegia in dogs. METHODS: Normal saline solution was circulated from the cisterna magna through an extracorporeal perfusion system consisting of a reservoir, a pump, and a heat exchanger, back into the subarachnoid space at the level of the medullary cone at a rate of 25 ml/min, starting 30 minutes before clamping, and ending after removal of the clamps. The thoracic aorta was cross-clamped below the left subclavian artery and above the diaphragm for a period of 45 minutes. Cerebrospinal fluid, intracranial, and central venous pressure and aortic pressure proximal, between, and distal to the clamps were continuously recorded. In five dogs, temperature of the circulating normal saline solution at the inflow level was maintained at 2 degrees +/- 1.5 degrees C (group 1), in five controls at 37 degrees +/- 0.8 degrees C (group 2). Five dogs underwent continuous cerebrospinal fluid drainage starting before clamping until sacrifice (group 3). Dogs were observed for up to 4 days, and neurologic function was graded by an independent observer with the Tarlov scale. Animals were then killed, and their spinal cords were prepared for microscopic examination. RESULTS: Hemodynamic parameters were not significantly different between groups. All dogs in groups 2 and 3 were paraplegic with histologic evidence of spinal cord infarction. All animals in group 1 were neurologically normal without microscopic evidence of infarction (p < 0.005). CONCLUSIONS: Selective deep hypothermia of the spinal cord prevents paraplegia after 45 minutes of double aortic clamping in dogs. Cerebrospinal fluid drainage was not effective in preventing paraplegia in this model.

Ischemia-reperfusion injury of the spinal cord: protective effect of the hydroxyl radical scavenger dimethylthiourea.

PURPOSE: This study was undertaken to evaluate whether neurologic outcome after aortic cross-clamping in rabbits could be improved with perioperative infusion of the hydroxyl radical scavenger dimethylthiourea and, if so, to determine whether it is effective during the period of ischemia, reperfusion, or both. METHODS: In 41 New Zealand White rabbits, a snare occlusion device was placed at operation around the infrarenal aorta and tunneled into a subcutaneous position. Animals were then allowed to recover and, 48 hours later, randomized into four groups. In each group, the infrarenal aorta was occluded by tightening the snare in the awake animal. In groups 1, 2, and 3, cross-clamp time was 21 minutes. Group 1 (control) animals received saline solution, whereas group 2 (preclamp 21) received dimethylthiourea 750 mg/kg intravenously just before aortic clamping. In group 3 (prerep 21), dimethylthiourea was given just before reperfusion. Group 4 received dimethylthiourea before clamping, with cross-clamp time extended to 31 minutes. A second dose of saline solution or dimethylthiourea was given 12 hours after clamping in controls and the three treatment groups, respectively. Animals were observed for 5 days, and final neurologic recovery was graded by an independent observer. Animals were then killed, and their spinal cords were removed for histologic examination. RESULTS: Complete paraplegia and marked histologic spinal cord injury at 5 days were seen in 91% (10/11) of group 1 (control) animals, whereas all animals in group 2 (preclamp 21) showed neurologic recovery (p < 0.0001). In group 3 (prerep 21), the final paraplegia rate was 50% (5 of 10), in group 4 (preclamp 31), 100% (10 of 10). CONCLUSIONS: Our results suggest that hydroxyl radicals play an important role in ischemia-reperfusion injury of the spinal cord and that treatment with dimethylthiourea can prevent paraplegia after 21 minutes of aortic cross-clamping in rabbits.