Repetitive control of electrical stimulation for tremor suppression

Tremor is a rapid uncontrollable back-and-forth movement of a body part often seen in patients with neurological conditions such as Multiple Sclerosis (MS) and Parkinson’s disease. This debilitating oscillation can be suppressed by applying functional electrical stimulation (FES) within a closedloop control system. However current implementations use classical control methods and have proved capable of only limited performance. This paper develops a novel application of repetitive control (RC) that exploits the capability of learning from experience to enable complete suppression of the tremor. The proposed control structure is applied to suppress tremor at the wrist via FES regulated co-contraction of wrist extensors/flexors. Experimental evaluation is performed using a validated wristrig and results are compared against classical feedback control designs to establish the efficacy of the approach

System identification for FES-based tremor suppression

Tremor is an involuntary motion which is a common complication of Parkinson's disease and Multiple Sclerosis. A promising treatment is to artificially contract the muscle through application of induced electrical stimulation. However, existing controllers have either provided only modest levels of suppression or have been applied only in simulation. To enable more advanced, model-based control schemes, an accurate model of the relevant limb dynamics is required, together with identification procedures that are suitable for clinical application. This paper proposes such a solution, explicitly addressing limitations of existing methodologies. These include model structures that (i) neglect critical features, and (ii) restrict the range of admissible control schemes, together with identification procedures that (iii) employ stimulation inputs that are uncomfortable for patients, (iv) are overly complex and time-consuming for clinical use, and (v) cannot be automated. Experimental results confirm the efficacy of the proposed identification procedures, and show that high levels of accuracy can be achieved in a short identification time using test procedures that are suitable for future transference to the clinical domain

Squamous Cell Carcinoma of the Descending Colon: Report of a Case and Literature Review

It is very rare that squamous cell carcinoma (SCC) arises from colorectal epithelium. An 89-year-old man was treated in 2001 with chief complaints of anorexia, abdominal pain, and low grade fever. The histological diagnosis as SCC was determined by biopsy during a colonoscopy. We diagnosed primary SCC of the colon because except in the colon no malignant lesions were found by systemic CT. Surgical complete resection was performed. However, he died three months after surgical resection because of hepatic metastasis and cachexia. The prognosis of this disease seems to be worse than that of adenocarcinoma

A dose-escalation study of indisulam in combination with capecitabine (Xeloda) in patients with solid tumours

This dose escalation study was designed to determine the recommended dose of the multi-targeted cell cycle inhibitor indisulam in combination with capecitabine in patients with solid tumours and to evaluate the pharmacokinetics of the combination. Thirty-five patients were treated with indisulam on day 1 of each 21-day cycle. Capecitabine was administered two times daily (BID) on days 1–14. Plasma concentrations of indisulam, capecitabine and its three metabolites were determined for pharmacokinetic analysis. The main dose-limiting toxicity was myelosuppression. Hand/foot syndrome and stomatitis were the major non-haematological toxicities. The recommended dose was initially established at indisulam 700 mg m−2 and capecitabine 1250 mg m−2 BID. However, during cycle 2 the recommended dose was poorly tolerated in three patients. A dose of indisulam 500 mg m−2 and capecitabine 1250 mg m−2 BID proved to be safe at cycle 1 and 2 in nine additional patients. Indisulam pharmacokinetics during cycle 1 were consistent with pharmacokinetic data from phase I mono-therapy studies. However, exposure to indisulam was remarkably increased at cycle 2 due to a drug–drug interaction between capecitabine and indisulam. Partial response was confirmed in two patients, one with colon carcinoma and the other with pancreatic carcinoma. Seventeen patients had stable disease. Indisulam (700 mg m−2) in combination with capecitabine (1250 mg m−2 BID) was well tolerated during the first cycle. A dose of indisulam 500 mg m−2 and capecitabine 1250 mg m−2 BID was considered safe in multiple treatment cycles. The higher incidence of toxicities observed during cycle 2 can be explained by a time-dependent pharmacokinetic drug–drug interaction

European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment

To develop a European guideline on pharmacologic treatment of Tourette syndrome (TS) the available literature was thoroughly screened and extensively discussed by a working group of the European Society for the Study of Tourette syndrome (ESSTS). Although there are many more studies on pharmacotherapy of TS than on behavioral treatment options, only a limited number of studies meets rigorous quality criteria. Therefore, we have devised a two-stage approach. First, we present the highest level of evidence by reporting the findings of existing Cochrane reviews in this field. Subsequently, we provide the first comprehensive overview of all reports on pharmacological treatment options for TS through a MEDLINE, PubMed, and EMBASE search for all studies that document the effect of pharmacological treatment of TS and other tic disorders between 1970 and November 2010. We present a summary of the current consensus on pharmacological treatment options for TS in Europe to guide the clinician in daily practice. This summary is, however, rather a status quo of a clinically helpful but merely low evidence guideline, mainly driven by expert experience and opinion, since rigorous experimental studies are scarce

Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma

Chimeric antigen receptor (CAR) therapy is a promising immunotherapeutic strategy for treating multiple refractory blood cancers, but further advances are required for solid tumor CAR therapy. One challenge is identifying a safe and effective tumor antigen. Here, we devise a strategy for targeting hepatocellular carcinoma (HCC, one of the deadliest malignancies). We report that T and NK cells transduced with a CAR that recognizes the surface marker, CD147, also known as Basigin, can effectively kill various malignant HCC cell lines in vitro, and HCC tumors in xenograft and patient-derived xenograft mouse models. To minimize any on-target/off-tumor toxicity, we use logic-gated (log) GPC3–synNotch-inducible CD147-CAR to target HCC. LogCD147-CAR selectively kills dual antigen (GPC3+CD147+), but not single antigen (GPC3-CD147+) positive HCC cells and does not cause severe on-target/off-tumor toxicity in a human CD147 transgenic mouse model. In conclusion, these findings support the therapeutic potential of CD147-CAR-modified immune cells for HCC patients