Copyright 2007 Surgery Litigation & Law Weekly via LawRx.com via NewsRx.com and NewsRx.net
Surgery Litigation & Law Weekly
May 4, 2007
SECTION: EXPANDED REPORTING; Pg. 1219

LENGTH: 1246 words

HEADLINE: CLEVELAND CLINIC, U.S.;
Cleveland Clinic, U.S., scientists detail new medical studies and findings

BODY:


Cleveland Clinic, U.S., scientists detail new medical studies and findings.

This trend article about Cleveland Clinic, U.S., is an immediate alert from NewsRx to identify developing directions of research.

Study 1: Data detailed in "The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease" have been presented. According to recent research published in the journal Nature Immunology, "T helper cells that produce interleukin 17 (IL-17) are associated with inflammation and the control of certain bacteria. We report here the essential involvement of the adaptor protein Act1 in IL-17 receptor (IL-17R) signaling and IL-17-dependent immune responses."

"After stimulation with IL-17, recruitment of Act1 to IL-17R required the IL-17R conserved cytoplasmic 'SEFIR' domain, followed by recruitment of the kinase TAK1 and E3 ubiquitin ligase TRAF6, which mediate 'downstream' activation of transcription factor NF-kappaB. IL-17-induced expression of inflammation-related genes was abolished in Act1-deficient primary astroglial and gut epithelial cells. This reduction was associated with much less inflammatory disease in vivo in both autoimmune encephalomyelitis and dextran sodium sulfate-induced colitis," wrote Y. Qian and colleagues, Cleveland Clinic, Department of Immunology.

The researchers concluded: "Our data show that Act1 is essential in IL-17-dependent signaling in autoimmune and inflammatory disease."

Qian and colleagues published their study in Nature Immunology (The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease. Nature Immunology, 2007;8(3):247-56).

For additional information, contact Y. Qian, Cleveland Clinic, Dept. of Immunology, Cleveland Ohio 44195 USA.

Study 2: Scientists have tested adoptive immunotherapy by allogeneic stem cell transplantation to treat metastatic renal cell carcinoma and report no objective response.

"A graft-versus-tumor effect through nonmyeloablative allogeneic stem cell transplantation (N-SCT) in metastatic renal cell carcinoma (RCC) has been reported. An Intergroup phase II trial was undertaken to define further the feasibility, toxicity and efficacy of this approach in a multi-institutional setting, Patients with cytokine-refractory, metastatic RCC were treated with N-SCT," scientists writing in the journal Biology of Blood and Marrow Transplantation reported.

"The conditioning regimen was fludarabine 30 mg. m(-2). d(-1) on day (d) -7 through d -3 and cyclophosphamide, 60 mg. kg(-1). d(-1) on d -4 and d -3. Patients received 2-8 X 106 CD34(+) cells/kg of granulocyte colony-stimulating factor mobilized stem cells from a 6/6 HLA-matched sibling donor. Immunosuppression after transplantation included tacrolimus and methotrexate. Twenty-two patients were enrolled at 14 institutions. Greater than 90% donor T-cell chimerism was observed in 17 of 19 evaluable patients (89%) by d +120," wrote B.I. Rini and colleagues, Cleveland Clinic Taussig Cancer Center.

"No objective response was observed. Acute graft-versus-host disease (GVHD) was observed in 11 patients (50%). Chronic GVHD was reported in 5 patients (23%). There was 1 patient death from liver failure secondary to chronic GVHD. Regimen-related mortality was 2 of 22 (9%; liver failure, sepsis). Median survival time was 5.5 months (95% confidence interval, 3.9-12.0 months) and the median time to progression was 3.0 months (95% confidence interval, 2.3-4.2 months). N-SCT for metastatic RCC is feasible in a multi-institutional setting. Adequate donor T-cell engraftment was achieved in most patients before disease progression. A graft-versus-tumor effect was not observed in this study despite acute and chronic GVHD, thus highlighting the need for further understanding of this approach," they reported.

The researchers concluded: "Allogeneic SCT remains investigational in RCC."

Rini and colleagues published their study in Biology of Blood and Marrow Transplantation (Adoptive immunotherapy by allogeneic stem cell transplantation for metastatic renal cell carcinoma: A CALGB Intergroup phase II study. Biol Blood Marrow Transplant, 2006;12(7):778-785).

Additional information can be obtained by contacting B.I. Rini, Cleveland Clinic Taussig Cancer Center, Dept. of Solid Tumor Oncology, 9500 Euclid Avenue, Desk R35, Cleveland, OH 44195, USA.

Study 3: Pressure-specified sensory device appears to be more sensitive than standard methods for evaluating diabetic neuropathy progress.

According to recent research from the United States, "Diabetic patients are more susceptible to the development of entrapment neuropathy than nondiabetics. Since these patients suffer from a slowly progressing diabetic polyneuropathy, standard neurosensory and motor tests of nerve function are not sufficient in the diagnosis of superimposed nerve compression. This is most evident in the early stages of compression when quantitative diagnosis is important for making decisions on surgical decompression."

M. Siemionow and colleagues at Cleveland Clinic evaluated "the validity of computer-assisted pressure-specified sensory device (PSSD) testing in the early detection of superimposed entrapment in diabetic neuropathy in comparison with standard clinical tests. Twenty-five diabetic patients with complaints of peripheral nerve dysfunction were evaluated by clinical tests and PSSD."

They found, "Out of those, nerve entrapment was detected in 15 patients (60%) (9 in late and 6 in early stage) by neurosensory PSSD testing. Standard clinical tests were confirmative in 33.3% of these cases (44% of late and 16.7% of early stage).

"Out of 144 evaluated nerves, 50 were diagnosed with entrapment (24 in late and 26 in early stage) using PSSD. Clinically, diagnosis was confirmed in 16% of entrapped nerves (20.8% of late and 11.5% of early stage). Average diabetes duration in patients with entrapment diagnosed using PSSD was significantly shorter than for those diagnosed clinically (4.14±2.04 vs. 7.2±1.3, respectively; p=0.005). Among evaluated factors, mean age and diabetes duration were found to be significantly shorter in patients with entrapment than in those with advanced diffused changes (54.47±13.07 vs. 67.10±14.2; p=0.019 and 5.33±3.74 vs. 14.22±8.17; p=0.006; respectively)."

"Our results revealed," concluded the authors, "higher sensitivity of PSSD in comparison with standard clinical tests in the detection of early-stage entrapment in patients with diabetes. To assess accuracy of PSSD in the proper patients' qualification for surgery, further prospective, postoperative studies are needed."

Siemionow and colleagues published their study in Annals of Plastic Surgery (Comparison of clinical evaluation and neurosensory testing in the early diagnosis of superimposed entrapment neuropathy in diabetic patients. Ann Plast Surg, 2006;57(1):41-49).

For additional information, contact M. Siemionow, Cleveland Clinic, Dept. of Plast Surgery A60, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

Keywords: Cleveland, Ohio, United States, Compressive Neuropathy, Critical Care Medicine, Diabetes, Diabetic Neuropathy, Endocrinology, Neurology, Neuropathy Early Diagnosis, Neuropathy Testing, Postoperative, Pressure-Specified Sensory Device.

This article was prepared by Surgery Litigation & Law Week editors from staff and other reports. Copyright 2007, Surgery Litigation & Law Week via NewsRx.com.

LOAD-DATE: April 27, 2007