IFNγ triggers a LIGHT-dependent selective death of motoneurons contributing to the non-cell-autonomous effects of mutant SOD1.

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that primarily affects motoneurons in the brain and spinal cord. Dominant mutations in superoxide dismutase-1 (SOD1) cause a familial form of ALS. Mutant SOD1-damaged glial cells contribute to ALS pathogenesis by releasing neurotoxic factors, but the mechanistic basis of the motoneuron-specific elimination is poorly understood. Here, we describe a motoneuron-selective death pathway triggered by activation of lymphotoxin-ß receptor (LT-ßR) by LIGHT, and operating by a novel signaling scheme. We show that astrocytes expressing mutant SOD1 mediate the selective death of motoneurons through the proinflammatory cytokine interferon-γ (IFNγ), which activates the LIGHT-LT-ßR death pathway. The expression of LIGHT and LT-ßR by motoneurons in vivo correlates with the preferential expression of IFNγ by motoneurons and astrocytes at disease onset and symptomatic stage in ALS mice. Importantly, the genetic ablation of Light in an ALS mouse model retards progression, but not onset, of the disease and increases lifespan. We propose that IFNγ contributes to a cross-talk between motoneurons and astrocytes causing the selective loss of some motoneurons following activation of the LIGHT-induced death pathway.

Accelerated treatment for early and late postpneumonectomy empyema.

BACKGROUND: Postpneumonectomy empyema is a rare but serious complication of pneumonectomy. Despite use of various therapeutic approaches and techniques during the last five decades, successful therapy remains difficult and is often associated with high morbidity and prolonged hospitalization. METHODS: We evaluated a concept for accelerated treatment, which consists of radical debridement of the pleural cavity and packing with wet dressings of povidoneiodine. This was repeated in the operating theater every second day, until the chest cavity was macroscopically clean. If present, bronchial stump insufficiency was closed and secured by omentopexy. Finally, the pleural space was obliterated with antibiotic solution. RESULTS: Twenty patients, 13 with early postpneumonectomy empyema (10 to 89 days; mean, 37 days) and 7 with late postpneumonectomy empyema (124 to 7,200 days; mean, 1,126 days) were treated. Fifteen patients presented with bronchopleural fistula (11 right, 4 left), which developed after chemotherapy (n = 6) or after radiotherapy (n = 3) (unknown cause in 4 patients). Six patients were referred after previously unsuccessful surgical attempts. Pleural cultures were positive in 17 cases for one or several bacteria including fungoides (n = 2). The average number of interventions was 3.5 (3 to 5). The chest was definitively closed in all patients within 8 days. Mean hospitalization time was 17 days (7 to 35 days). During the same hospitalization, 2 patients needed reoperation because of an undetected bronchopleural fistula. Postpneumonectomy empyema was successfully treated in all patients. There was no in-hospital or 3-month postoperative mortality. CONCLUSIONS: Repeated surgical debridement combined with closure of bronchopleural fistula and antimicrobial therapy enables successful treatment of early and late postpneumonectomy empyema within a short period and is a well-tolerated concept.

Surveillance of peripheral arterial bypass grafts with three-dimensional MR angiography: comparison with digital subtraction angiography.

OBJECTIVE: The purpose of this study was to use contrast-enhanced three-dimensional MR angiography to assess the patency of peripheral arterial bypass grafts of the lower extremity. SUBJECTS AND METHODS: The study included 39 patients with 45 lower limb grafts. Twenty-eight were saphenous vein grafts, 13 were expanded polytetrafluoroethylene, and two were Dacron grafts. Digital subtraction angiography correlation was available for 30 patients (31 grafts). MR angiography was performed on a 1.5-T system with a multichannel quadrature phased array peripheral vascular coil. The scanning delay was determined with a test bolus technique, using half-time to maximum signal intensity in the graft. Arterial imaging was accomplished with two three-dimensional MR angiography acquisitions with gadopentetate dimeglumine administered using an automated injector. The pelvic and femoral arteries were imaged, the MR table was repositioned, and the lower limb arteries were imaged. The three-dimensional MR angiography sequence used the following parameters: TR/TE, 5.2/1.5 msec; inversion time, 28 msec; flip angle, 30 degrees. The proximal anastomosis, graft, and distal anastomosis were characterized as normal, stenosed, occluded, or ectatic or aneurysmatic. RESULTS: Sensitivity and specificity values for MR angiography regarding the assessment of grafts were 100% for 87 evaluable segments for which digital subtraction angiography correlation was available: stenosis (n = 10), occlusions (n = 9), ectasia or aneurysms (n = 8). Six segments could not be assessed because of the presence of intravascular stents or metallic clips. CONCLUSION: Contrast-enhanced three-dimensional MR angiography is well suited for the characterization of arterial grafts, for planning subsequent vascular interventions, and for excluding further lesions.

Repair of infrapopliteal postembolectomy complications with variant embolization techniques.

Infrapopliteal pseudoaneurysms and arteriovenous fistulae are known complications of Fogarty balloon embolectomy. Management of these complications in two patients with associated critical foot ischemia by modified interventional embolization techniques is described.

Leg ulcers in peripheral arterial disease (arterial leg ulcers): impaired wound healing above the threshold of chronic critical limb ischemia.

BACKGROUND: Peripheral arterial disease is the only identifiable etiology in approximately 10% of leg ulcers. Clinical data on the management of these chronic wounds are scarce. OBJECTIVE: We attempted to outline the threshold of systolic ankle pressure and ankle-brachial-index (ABI) below which arterial leg ulcers can occur and to outline the indication for revascularization in arterial leg ulcers. METHODS: Diagnostic and outcome analysis was performed for 26 consecutive patients with arterial leg ulcers. We calculated sensitivities, specificities, and receiver operating characteristic (ROC) curves for the identification of arterial leg ulcers among all 223 consecutive leg ulcer patients within a 3-year period, as well as the ROC curve for patients who required revascularization. RESULTS: The systolic ankle pressure was 88 (18-130) mm Hg (median; 95% confidence interval) and the ABI was 0.60 (0.15-0.86), respectively. Eighteen patients (69%) were subjected to revascularization. By the end of the study, 24 patients (92%) healed completely, 1 improved (90% wound closure), and 1 patient had to undergo below-knee amputation for chronic osteomyelitis. During this study, the ankle pressure and ABI were poor in distinguishing those patients who required revascularization from those who healed without revascularization. CONCLUSION: Most arterial leg ulcers do not meet the criteria of chronic critical limb ischemia, but they do not heal under conservative measures, either. A majority of these patients benefit from revascularization and should, therefore, be referred for arterial duplex ultrasound investigation or angiography. In our study, an ankle pressure below 110 mm Hg identified all patients (100%) who were subjected to revascularization procedures. However, controlled clinical studies are required to find the systolic ankle pressure and ABI below which revascularization can be recommended to speed up the healing time.

Management of leg ulcers in patients with rheumatoid arthritis or systemic sclerosis: the importance of concomitant arterial and venous disease.

PURPOSE: We assessed the etiology and the prevalence of peripheral arterial and venous disease in leg ulcers in patients with rheumatoid arthritis and systemic sclerosis and analyzed the outcome after treatment of macrovascular disease. METHODS: A clinical study on 15 consecutive patients with chronic leg ulcers in collagen vascular disease (nine patients with rheumatoid arthritis, six patients with systemic sclerosis) was carried out in a referral center. Angiography was used when the ankle-arm index was less than 0.8; venography was used when venous reflux was detectable by means of a hand-held Doppler examination. Therapies included percutaneous transluminal angioplasty (seven patients), femoropopliteal bypass grafting surgery (one patient), saphenectomy of the greater saphenous vein (six patients), and split skin graft (11 patients). RESULTS: All patients with rheumatoid arthritis exhibited a multifactorial etiology of their ulcers: four of nine patients had peripheral arterial disease, and five of nine patients had venous insufficiency. In one of these patients, arterial and venous disease was combined. Five of six patients with systemic sclerosis exhibited a multifactorial etiology of their ulcers: three of six patients had peripheral arterial disease, and three of six patients had venous insufficiency. One of these patients had both arterial and venous disease. In patients with rheumatoid arthritis, healing was achieved in six of nine patients, and marked improvement occurred in two of nine patients. A below-knee amputation was necessary in one patient with rheumatoid vasculitis. In patients with systemic sclerosis, healing was achieved in three of six patients, and marked improvement occurred in the other three patients. CONCLUSION: Most leg ulcers in patients with rheumatoid arthritis and systemic sclerosis disclose a multifactorial etiology. Relevant arterial and venous disease can be found in approximately half the patients. Our study suggests that revascularization and vein surgery improve the healing of leg ulcers in patients with collagen vascular disease. A prospective trial is now required to confirm these results.

Juxtaacetabular ganglion as a differential diagnosis in pulsating groin masses.

Ganglion cysts of the hip joint are uncommon synovial-lined fluid-filled juxtaarticular groin lesions. Whereas in the past the correct diagnosis was often made only at surgery there are now valuable imaging methods used for the diagnostic work-up. In experienced hands ultrasonography (US) combined with colour duplex Doppler ultrasonography (CDDS) as a real-time imaging technique easily performed at the patient's bedside is a valid alternative to more expensive or invasive investigations. We report on a patient who presented with a ganglion cyst and in whom first supported by conventional US an aneurysm of the femoral artery was suspected. The diagnosis of a juxtaarticular ganglion was subsequently correctly made at our institution by CDDS and magnetic resonance imaging, respectively, and the cyst was exstirpated successfully. The differential diagnosis of a pulsating groin mass as well as the most useful and specific imaging methods in the diagnostic work-up in this clinical setting are discussed.

Ligating clips for three-dimensional MR angiography at 1.5 T: in vitro evaluation.

Artifact size on three-dimensional (3D) magnetic resonance (MR) angiograms and safety of various vascular clips (15 titanium and three absorbable polydioxanone clips) were assessed. All evaluated clips were completely safe. Biodegradable clips rendered no artifacts; titanium clips were associated with susceptibility effects. Artifact size was dependent on clip size, clip orientation, echo time, and degree of k-space coverage. In the presence of titanium vascular clips, fast 3D MR angiography should be performed with the shortest echo time and full k-space coverage.

Ultrasound scans done by surgeons for patients with acute abdominal pain: a prospective study.

OBJECTIVE: To evaluate the routine use of abdominal ultrasonography (US) in patients admitted to the surgical emergency unit with acute abdominal pain. DESIGN: Prospective study with a three-step evaluation of patients over a 12-month period. SETTING: University hospital, Switzerland. SUBJECTS: 496 patients (male/female = 234/262; mean age 45 years) who presented with acute abdominal pain. INTERVENTIONS: Every patient underwent routine investigations and had an abdominal US by the attending surgeon. MAIN OUTCOME MEASURES: Clinical diagnosis, post-ultrasonography diagnosis and final diagnosis. RESULTS: US improved the correct diagnostic rate from 348 (70%) to 414 (83%). The diagnostic accuracy for acute appendicitis and biliary tract disease improved after US from 455 (92%) to 488 (98%) and from 463 (93%) to 490 (99%), respectively; the corresponding sensitivities and specificities were 91% and 99% and 94% and 99%. CONCLUSIONS: Ultrasonography should be part of routine surgical investigation and should be mastered and used by surgeons.

The real incidence of percutaneous injuries in the operating room--a prospective study.

Despite the frequent exposure of operating room personnel to blood and other body fluids and the obvious risk of occupational transmission of HIV infection, the real incidence of injuries after needle sticks or cuts in the operating room has not been well investigated. Every injury occurring in the operating room during one thousand consecutive elective and emergency procedures was studied and the risk for acquiring an HIV infection was calculated. There were 50 injuries during 761 elective procedures (6.6%) and 23 injuries during 239 emergency operations (9.6%). There was one single injury during 91 minimally invasive endoscopical procedures (1.1%). The surgeon was the person most frequently injured (3.5%). The injury rate of the scrub nurse varied between 1.4% and 2.8% according to the surgeon's experience. The operating room personnel is at risk for an occupational transmission of blood born pathogens. If the seroprevalence of HIV in surgical patients is estimated at 0.4% the calculated probability for a surgeon to acquire HIV infection over a 30-year career amounts to 0.3%.

Video-assisted thoracoscopy in the treatment of pleural empyema: stage-based management and outcome.

OBJECTIVE: Despite modern diagnostic methods and appropriate treatment, pleural empyema remains a serious problem. Our purpose was to assess the feasibility and efficacy of the video-assisted thoracoscopic surgery in the management of nontuberculous fibrinopurulent pleural empyema after chest tube drainage treatment had failed to achieve the proper results. METHODS: We present a prospective selected single institution series including 45 patients with pleural empyema who underwent an operation between March 1993 and December 1996. Mean preoperative length of conservative management was 37 days (range, 8-82 days). All patients were assessed by chest computed tomography and ultrasonography and underwent video-assisted thoracoscopic debridement of the empyema and postoperative irrigation of the pleural cavity. RESULTS: In 37 patients (82%), video-assisted thoracoscopic debridement was successful. In 8 cases, decortication by standard thoracotomy was necessary. There were no complications during video-assisted thoracic operations. The mean duration of chest tube drainage was 7. 1 days (range, 4-140 days). At follow-up (n = 35) with pulmonary function tests, 86% of the patients treated by video-assisted thoracic operation showed normal values; 14% had a moderate obstruction and restriction without impairment of exercise capacity, and no relapse of empyema was observed. CONCLUSIONS: Video-assisted thoracoscopic debridement represents a suitable treatment for fibrinopurulent empyema when chest tube drainage and fibrinolytics have failed to achieve the proper results. In an early organizing phase, indication for video-assisted thoracic operation should be considered in due time to ensure a definitive therapy with a minimally invasive intervention. For pleural empyema in a later organizing phase, full thoracotomy with decortication remains the treatment of choice.

Two-year results after lung volume reduction surgery in alpha1-antitrypsin deficiency versus smoker's emphysema.

Lung volume reduction surgery (LVRS) improves exercise capacity and relieves dyspnoea in patients with smoker's emphysema (SE). It is unclear, however, whether LVRS similarly improves lung function in alpha1-antitrypsin-deficiency emphysema (alpha1 E). To address this question, this study prospectively compared the intermediate-term functional outcome in 12 consecutive patients with advanced alpha1E and 18 patients with SE who underwent bilateral LVRS. Before surgery there were no statistically significant differences between the two groups in the six-minute walking distance, dyspnoea score, respiratory mechanics or lung function data, except for the forced expiratory volume in one second, which was lower in the deficient group (24 versus 31% of the predicted value; p<0.05). In both groups, bilateral LRVS produced significant improvements in dyspnoea, the six-minute walking distance, lung function and respiratory mechanics. In the alpha1E group, the functional data, with the exception of the six-minute walking distance, returned to baseline at 6-12 months postoperation and showed further deterioration at 24 months. The functional status of the SE group remained significantly improved over this period. In conclusion, the functional improvements resulting from bilateral lung volume reduction surgery are sustained for at least 2 yrs in most patients with smoker's emphysema, but this type of surgery offers only short-term benefits for most patients with alpha1E.

Infrainguinal aneurysm formation in arterialized autologous saphenous vein grafts.

True aneurysm formation in arterialized autologous veins is an unusual complication. We studied a patient with 2 aneurysms occurring in the mid and distal portion of an in situ femoropopliteal bypass. The first aneurysm led to graft occlusion 4 years after the primary intervention, requiring replacement of the ectatic graft segment. The graft was still patent when the patient was examined 7 years after the primary intervention and 3 years after the first aneurysm. In the mid portion of the graft, a true aneurysm measuring 5 by 8 cm had developed. The aneurysm was replaced by a reversed segment of the contralateral greater saphenous vein. Recovery was uneventful. Advanced atherosclerotic changes with extensive intimal fibroplasia, subendothelial cholesterol deposits, and ulcerations were revealed by means of histopathology of the aneurysm wall. Atherosclerosis is considered to be the main cause of aneurysm formation in vein grafts, but a review of the literature suggests the additional etiopathogenic factors should be further investigated.

Catamenial hemoptysis. Diagnosis with MRI.

Thoracic endometriosis is a rare disorder. We report a case of a 26-year-old woman with a 4-year history of catamenial hemoptysis due to thoracic endometriosis which was diagnosed by MRI and treated successfully by means of video-assisted thoracoscopic wedge-resection of the solitary pulmonary lesion. Medical therapy with hormones was not necessary. There is no evidence of recurrence 10 months after the operation. This case demonstrates that MRI of the chest may be considered for the diagnostic work-up of patients with catamenial hemoptysis. It also shows that wedge-resection of pulmonary endometriosis foci by means of video-assisted thoracoscopy-an approach that has not been described in the literature thus far-is an effective therapy in localized peripheral pulmonary parenchymal endometriosis.

[Indications and results of para-sternal mediastinoscopy in tumors of the anterior mediastinum]. / Indikation und Ergebnisse der parasternalen Mediastinoskopie bei Tumoren im vorderen Mediastinum.

From January 1990 to December 1995 79 patients with mediastinal lesions were seen for parasternal mediastinoscopy at the Ruhrlandklinik Essen. Diagnosis was achieved in 91.1%. In 7 cases (8.9%) the diagnosis was not established. Six intraoperative complications occurred following mediastinoscopy: minor bleeding in five instances from the internal mammary vessels and one significant bleeding by injuring the V. cava. Postoperative minor wound infections occurred in five patients. Two pneumothoraces had to be managed by chest tube drainage. One patient with metastatic lung cancer died of respiratory failure.

[Efficacy of basic surgical diagnosis in acute abdominal pain]. / Die Effizienz der chirurgischen Grunddiagnostik beim akuten Abdominalschmerz.

This report describes a retrospective study concerning 314 patients suffering from acute abdominal pain admitted to the surgical emergency unit of Zürich University Hospital in 1992. Basic diagnostic work-up (history, physical examination, blood tests, sonography and abdominal X-ray) revealed the final diagnosis in 188 patients. Sonography was essential in 77 cases. Only 33 patients required additional examinations, such as CT-scan, gastroscopy or contrast X-rays. Ninety-three patients were discharged with a final diagnosis of "non-specific abdominal pain" (NSAP) after their symptoms had improved. A follow-up examination of these patients 6-18 months later resulted in a final diagnosis of somatic diseases in 8% of cases. This study demonstrated that the basic surgical diagnostics are efficient and reveal the final diagnosis with minimal delay. Abdominal sonography is the most important diagnostic tool in this context and should, therefore, be mastered and employed by the surgeon himself.