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This multicentre phase II study evaluated the efficacy and safety of preoperative capecitabine plus oxaliplatin and radiotherapy (RT) in patients with locally advanced rectal cancer (T3/T4 rectal adenocarcinoma with or without nodal involvement). Treatment consisted of one cycle of XELOX (capecitabine 1000 mg m(-2) bid on days 1-14 and oxaliplatin 130 mg m(-2) on day 1), followed by RT (1.8 Gy fractions 5 days per week for 5 weeks) plus CAPOX (capecitabine 825 mg m(-2) bid on days 22-35 and 43-56, and oxaliplatin 50 mg m(-2) on days 22, 29, 43 and 50). Surgery was recommended 5 weeks after completion of chemoradiotherapy. The primary end point was pathological complete tumour response (pCR). Sixty patients were enrolled. In the intent-to-treat population, the pCR rate was 23% (95% CI: 13-36%). 58 patients underwent surgery; R0 resection was achieved in 57 (98%) patients, including all 5 patients with T4 tumours. Sphincter preservation was achieved in 49 (84%) patients. Tumour and/or nodal downstaging was observed in 39 (65%) patients. The most common grade 3/4 adverse events were diarrhoea (20%) and lymphocytopaenia (43%). Preoperative capecitabine, oxaliplatin and RT achieved encouraging rates of pCR, R0 resection, sphincter preservation and tumour downstaging in patients with locally advanced rectal cancer.

Hypoxic pulmonary vasoconstriction is associated with but may not be sufficient for the development of high-altitude pulmonary oedema (HAPO). Hypoxia is known to induce an inflammatory response in immune cells and endothelial cells. It has been speculated that hypoxia-induced inflammatory cytokines at high altitude may contribute to the development of HAPO by causing capillary leakage in the lung. We were interested if such an inflammatory response, possibly involved in a later development of HAPO, is detectable at high altitude in individuals without HAPO. We examined the plasma levels of interleukin 6 (IL-6), interleukin 1 receptor antagonist (IL-1ra) and C-reactive protein (CRP) in two independent studies: study A, Jungfraujoch, Switzerland, three overnight stays at 3458 m, n=12; study B: Capanna Regina Margherita, Italy, 3 overnight stays at 3647 m and one overnight stay at 4559 m, n=10. In both studies, probands showed symptoms of acute mountain sickness but no signs of HAPO. At the Jungfraujoch, IL-6 increased from 0.1+/-0.03 pg/ml to 2. 0+/-0.5 pg/ml (day 2, P=0.03), IL-1ra from 101+/-21 to 284+/-73 pg/ml (day 2, P=0.01), and CRP from 1.0+/-0.4 to 5.8+/-1.5 micrograms/ml (day 4, P=0.01). At the Capanna Margherita, IL-6 increased from 0. 5+/-0.2 pg/ml to 2.0+/-0.8 pg/ml (P=0.02), IL-1ra from 118+/-25 to 213+/-28 pg/ml (P=0.02), and CRP from 0.4+/-0.03 to 3.5+/-1.1 micrograms/ml (P=0.03). IL-8 was below the detection limit of the ELISA (

Recently, the first apheresis technique for direct adsorption of low-density lipoprotein (LDL) and lipoprotein(a) [Lp(a)] from whole blood (DALI) was developed that does not require a prior plasma separation. That markedly simplifies the extracorporeal circuit. The aim of the present study was to test the acute biocompatibility, efficacy, and selectivity of DALI apheresis. In a prospective clinical study, 6 hypercholesterolemic patients suffering from angiographically proven atherosclerosis were treated 4 times each by DALI. 1.3 patient blood volumes were treated per session at blood flow rates of 60-80 ml/min using 750 or 1,000 ml of polyacrylate/polyacrylamide adsorber gel. The anticoagulation consisted of an initial heparin bolus followed by a citrate infusion. The sessions were clinically essentially uneventful. Mean corrected reductions of lipoproteins amounted to 65% for LDL-cholesterol, 54% for Lp(a), 28% for triglycerides, 1% for HDL-cholesterol, and 8% for fibrinogen. The selectivity of lipoprotein removal was high. Cell counts remained virtually unchanged and no signs of hemolysis or clotting were detected. Cell activation parameters elastase, beta-thromboglobulin, interleukin-1beta, and IL-6 showed no significant increase. Complement activation was negligible. There was significant, but clinically asymptomatic, bradykinin activation in the adsorber with mean maxima of 12,000 pg/ml in the efferent line at 1,000 ml of treated blood volume. In conclusion, DALI proved to be safe, selective, and efficient for the adsorption of LDL-C and Lp(a), which simplifies substantially the extracorporeal therapy in hypercholesterolemic patients.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder, characterized by progressive loss of motor neurons. However, ALS has been recognized to involve several non-motor systems. Subclinical involvement of the autonomic system (i.e. of cardial or sudomotor regulation) has been described in ALS. Gastrointestinal motor dysfunction can occur in amyotrophic lateral sclerosis, even if patients do not complain of gastrointestinal symptoms. New techniques in non-invasive evaluation of gastrointestinal function showed delayed gastric emptying and delayed colonic transit times in patients with ALS.

Four children from two families with characteristics of Marinesco-Sjögren syndrome (congenital cataract, ataxia) are presented. All children had clinical and neurophysiological signs of a demyelinating polyneuropathy. Three of them developed acute rhabdomyolysis with marked weakness and CK levels of up to 40,000 U/I following a viral infection. In all children CK levels returned to normal within two weeks. Symptoms were recurrent in one of the children and resulted in a severe disability. In two other children recovery of motor function took about a month following the first attack. Metabolic disorders of the muscle were excluded by pathobiochemical examination of a muscle biopsy in one of the children. In conclusion, acute rhabdomyolysis can occur as a neuromuscular complication of Marinesco-Sjögren syndrome.

Objective To report on 3 patients with inflammatory demyelinating peripheral neuropathy in strong temporal coincidence with the initiation of peritoneal dialysis (PD) therapy. Setting Nephrology and Neurology Department of the University Hospital, Munich, Germany. Patients Three patients with end-stage renal failure presented with the clinical picture of inflammatory demyelinating peripheral neuropathy within 4 to 10 weeks after start of continuous ambulatory peritoneal dialysis (CAPD). They had acute or subacute onset of lower extremity or generalized weakness, diminished reflexes, elevated spinal fluid protein levels, and signs of demyelinating neuropathy on electrophysiological testing. Measures Clinical follow-up, nerve conduction studies, cerebral spinal fluid (CSF). Results All patients did not improve under intensified PD therapy but took profit from immunomodulatory therapy. One bed-bound patient improved after change to hemodialysis and showed complete remission after renal transplantation. Conclusion Because of strong temporal coincidence, a causal relationship between CAPD and inflammatory demyelinating peripheral neuropathies can be suspected in these 3 patients.

Eine 50jahrige Patientin wurde wegen rasch progredienter Gangunsicherheit, Parasthesien und wiederholt einschiesenden, zum Teil sehr schmerzhaften Muskelkontraktionen an Armen und Beinen stationar aufgenommen. Als Ursache der Beschwerden fand sich ein kleinzelliges Bronchialkarzinom (T2 N3 M0) mit Nachweis von Anti-Hu-Autoantikorpern (zytoplasmatische antineuronale Antikorper). Die neurologische Symptomatik konnte nach Ausschlus anderer Ursachen als paraneoplastische subakute zerebellare Degeneration, paraneoplastische subakute sensorische Neuronopathie (SSN), paraneoplastische Myoklonien und paraneoplastische Neuromyotonie eingestuft werden. Mit Remission des Tumors unter Chemotherapie waren Anti-Hu-Antikorper nicht mehr nachweisbar, und die neurologische Symptomatik bildete sich vollstandig zuruck. Die Kasuistik zeigt, das die paraneoplastische Bildung von Anti-Hu-Autoantikorpern eine Vielzahl neuronaler Funktionssysteme betreffen und damit verschiedene neurologische Symptome bedingen kann.

A middle-aged patient presented with subacute muscular stiffness, myocloni of both extremity and facial muscles, gait ataxia and symmetrical distal painful paraesthesias. Electrophysiologically, neuromyotonia was confirmed. High titer anti-Hu antibodies were detected, but no other paraneoplastic antibodies were found. Small-cell lung cancer was diagnosed. Under chemotherapy tumor remission was achieved and, except for minor sensory deficits, neurological symptoms disappeared. This report shows that paraneoplastic syndromes associated with antibodies to neuronal nucleoproteins (anti-Hu antibodies) may be associated with a syndrome including neuromyotonia, sensory neuropathy, cerebellar symptoms and myocloni.

Extracorporeal procedures for the elimination of autoantibodies are an important therapeutic option in various neuroimmunological diseases, especially those with neuromuscular involvement. Recent advances with the development of selective apheresis methods have given extracorporeal therapeutic procedures a new perspective. In this article, we review the therapeutic use of plasma exchange and immunoadsorption therapy in different neuroimmunological diseases.

Corresponding Author: Michael Schmuecking, MD E-Mail: michael.schmuecking@insel.ch Inclusion criteria: Informed consent, histologically proven NSCLC stage I or hypermetabolic oligometastatic lung lesions. Peripheral or central localization, maximal tumor diameter of 45mm. Karnofsky index > 60%. Medically inoperable. Moving of the lung lesion during breathing less than 5mm as detected by 4D-CT. Initial staging: whole body 18F-FDG PET/CT in radiation treatment position, MRI of the brain. Optional for staging: 18F-FDG PET/CT of the lung in breath hold technique in radiation treatment position. Radiation treatment planning: 4D-CT and angio-CT in radiation treatment position for target volume delineation. BodyFIX® vacuum cushions for comfortable, accurate and reproducible patient positioning during radiation treatment. Using 4DCT for target volume delineation, a Boolean operation was used to sum the multiple gross target volumes (GTV) delineated in diagnostic lung window to form an internal target volume (ITV). The planning target volume was derived by a three-dimensional isotropic expansion of the ITV by 5mm to account for both microscopic extension and daily setup errors. Using non-gated PET/CT (frame mode) for target volume delineation of the ITV the iso-line of SUV 2.5 was used or the tumor/background algorithm as proposed by Nestle et al. JNM 2005. For 16/22 lung lesions the prescription dose was 5 x 12 Gy, for 1/22 centrally located lung lesion the prescription dose was 5 x 10 Gy, for the initial 5/22 lesions the prescription dose was 5 x 7 Gy. For all patients the prescription isodose was the 80% line (prescription line identical with the planning target volume). Maximal time for follow-up: 21 months, mean time for follow-up: 13 months. By design, stereotactic body radiotherapy (SBRT) is applied to small treatment volumes, using fewer but significantly higher dose fractions, and steep dose gradients – all of which act to maximize cell kill and minimize the risk of damage to the surrounding normal tissues.

A randomized two-part study was conducted in order to determine the efficacy of theophylline in the treatment of acute mountain sickness during fast ascent to altitudes >2,500 m. Fourteen healthy male subjects participated in a randomized single-blind placebo-controlled crossover study carried out in a decompression chamber (simulated altitude 4,500 m). A second randomized single-blind, placebo-controlled study was conducted at a high-altitude research laboratory (3,454 m) and included 21 healthy male subjects. The study medication was either 375 mg oral slow-release theophylline (250 mg if

Transforming growth factors-beta 1, 2, and 3 are known for their regulatory function in embryogenesis, fibrogenesis, and tissue repair of different cell types. A trophic function of TGF-beta subclasses for motoneurons has been shown in vitro. TGF-beta 1 is a potent survival factor for cultured embryonic rat motoneurons. In addition, TGF-beta 1 stimulates proliferation of rat Schwann cells. Recently, TGF-beta 2 has been reported to be associated with the subsynaptic nuclei of mature rat neuromuscular junctions. In this study, we investigated the expression of TGF-beta 1, 2, and 3 at neuromuscular junctions in skeletal muscle of 11 adults without neuromuscular disease. On muscle biopsies, neuromuscular junctions were depicted by acetylcholine esterase reaction and acetylcholine receptor antibodies. TGF-beta 1; 2, and 3 were stained immunohistochemically with monoclonal antibodies. Some muscle fibers showed low levels of inhomogeneous immunoreactivity for both TGF-beta 1 and TGF-beta 3. Intense immunoreactivity of TGF-beta 1 and 3 was shown at the postsynaptic area of neuromuscular junctions. TGF-beta 2 was expressed in the same subcellular distribution, but less strongly. In conclusion, the colocalization of TGF-beta with neuromuscular junctions may suggest a significant function in neuromuscular communication.

This is the report of a late-onset carbamazepine-induced systemic lupus erythematosus in a 34-year-old patient who had been treated with daily carbamazepine for 8 years because of complex partial seizures. When carbamazepine was discontinued, symptoms rapidly improved and antinuclear antibodies disappeared. So far, few cases have been reported of carbamazepine-induced lupus erythematosus within months after the start of treatment. This is the first case report about carbamazepine-induced systemic lupus erythematosus with serological confirmation after years of treatment without side effects.

In previous studies, ultrasonography was a very sensitive method in detecting fasciculations. The present study was intended to examine the prevalence of ultrasonographically visible fasciculations in patients with neuromuscular diseases affecting the lower extremities. Ultrasonography of 9 muscles (rectus femoris, vastus lateralis, vastus intermedius, vastus medialis, sartorius, semitendinosus, tibialis anterior, gastrocnemius, and soleus muscles) was performed bilaterally in 70 adult healthy subjects and 172 patients with various neuromuscular diseases. Fasciculations were detected in 109 (63%) of 172 patients. The median value of affected muscles was 10 (range 1-18). Patients with spinal muscular atrophy (37/38, p < 0.001), hereditary motor and sensory neuropathy (24/25, p < 0.001), and lumbosacral radiculopathy with motor deficits (24/29, p < 0.001) exhibited fasciculations more frequently than did healthy volunteers. Radiculopathy with sensory deficits, lesions of either plexus or peripheral nerves, compartment syndrome, and myopathy were not associated with a significantly enhanced prevalence of fasciculations in the patient group compared to the control group. In summary, fasciculations are a frequent ultrasonographic sign in neuromuscular diseases. They are almost regularly found in patients with spinal muscular atrophy and those with hereditary motor and sensory neuropathy. Thus, the absence of fasciculations in ultrasonographic assessment should give cause for reconsidering these diagnoses.

Acute mountain sickness (AMS) is characterized by headache often accompanied by gastrointestinal complaints that vary from anorexia through nausea to vomiting. The aim of this study was to investigate the influence of high altitude on plasma levels of gastroenteropancreatic (GEP) peptides and their association to AMS symptoms. Plasma levels of 6 GEP peptides were measured by radioimmunoassay in 11 subjects at 490 m (Munich, Germany) and, after rapid passive ascent to 3454 m (Jungfraujoch, Switzerland), over the course of three days. In a second study (n = 5), the same peptides and ghrelin were measured in subjects who consumed standardized liquid meals at these two elevations. AMS symptoms and oxygen saturation were monitored. In the first study, both fasting (morning 8 a.m.) and stimulated (evening 8 p.m.) plasma levels of pancreatic polypeptide (PP) and cholecystokinin (CCK) were significantly lower at high altitude as compared to baseline, whereas gastrin and motilin concentrations were significantly increased. Fasting plasma neurotensin was significantly enhanced whereas stimulated levels were reduced. Both fasting and stimulated plasma motilin levels correlated with gastrointestinal symptom severity (r = 0.294, p = 0.05, and r = 0.41, p = 0.006, respectively). Mean O(2)-saturation dropped from 96% to 88% at high altitude. In the second study, meal-stimulated integrated (= area under curve) plasma CCK, PP, and neurotensin values were significantly suppressed at high altitude, whereas integrated levels of gastrin were increased and integrated VIP and ghrelin levels were unchanged. In summary, our data show that acute exposure to a hypobaric hypoxic environment causes significant changes in fasting and stimulated plasma levels of GEP peptides over consecutive days and after a standardized meal. The changes of peptide levels were not uniform. Based on the inhibition of PP and neurotensin release a reduction of the cholinergic tone can be postulated.

Reactivation of Chronic Hepatitis C Virus Infection by Immunoadsorption in Factor VIII Inhibitor Haemophilia

Reduction of Acquired High Titer Factor VIII Antibodies by Extracorporeal Antibody-based Immunoadsorption without Additional Immunosuppressive Therapy

1998;113;1428 Chest Hautmann, Matthias Tschop, Rainald Fischer and Rudolf M. Huber Marcell Toepfer, Gunther Hartmann, Maximilian Schlosshauer, Hubert Adrenomedullin: A Player at High Altitude? http://chestjournal.chestpubs.org/content/113/5/1428.2.citation services can be found online on the World Wide Web at: The online version of this article, along with updated information and ISSN:0012-3692 ) http://chestjournal.chestpubs.org/site/misc/reprints.xhtml ( written permission of the copyright holder. this article or PDF may be reproduced or distributed without the prior Dundee Road, Northbrook, IL 60062. All rights reserved. No part of Copyright1998by the American College of Chest Physicians, 3300 Physicians. It has been published monthly since 1935. is the official journal of the American College of Chest Chest