Emerging drugs in lung transplantation.

The balance between immunosuppression to ensure graft tolerance while preventing emergence of infectious complications is key in lung transplantation. Although opportunistic infection may appear to be the most important of these complications, malignancies and severe drug toxicities significantly affect the short- and long-term outcomes of the patients. The present practice is combination therapy using drugs with complementary immunosuppressive action, to achieve synergistic immunosuppression with the lowest possible toxicity. Components of immunosuppression include induction and maintenance regimens. Primary graft failure remains an important cause of mortality and morbidity in the immediate post-transplant period. Acute rejection is a common complication after lung transplant, but responds well to augmented immunosuppression and immunomodulation. Chronic rejection still is the major cause of mortality in patients who survive the initial year post-transplantation. Several new drugs have shown promise in decreasing the rate of loss of graft function. This review discusses the current and emerging therapeutic regimens.

Intravenous flumazenil for Parkinson's disease: a single dose, double blind, placebo controlled, cross-over trial.

Flumazenil is a short-acting intravenously administered gamma-aminobutyric acid (GABA) antagonist used to reverse the effects of benzodiazepines. Based upon current basal ganglion models in Parkinson's disease (PD), flumazenil could normalize neuronal signaling at several different locations. We conducted a double-blind, placebo controlled, single dose, cross-over trial of flumazenil and placebo in 16 subjects with PD. Subjects were primarily assessed with serial tapping tests (1 minute for each hand) at 15-minute intervals for 90 minutes after infusion. Secondary assessments included the Unified Parkinson's Disease Rating Scale (UPDRS) Motor part at baseline and 45 minutes after infusion, and global impressions. Subjects then underwent a 90-minute washout and entered the opposite arm of the cross-over. Change in tapping speed compared to baseline improved throughout the 90-minute period (P < 0.0001) and at each individual time (P < 0.01), except for 15 minutes status after infusion, with flumazenil compared to placebo. UPDRS scores tended to improve more on drug, but this finding was not significant. The medication was well tolerated. The most common adverse event on drug was a sense of "light-headedness" or "dizziness." GABA antagonists represent a novel potential treatment class for PD.

Emerging drugs in Tourette syndrome.

Proper education of the patient is the first step in the treatment of Tourette syndrome (TS). Before deciding how to treat the patient, it is important to decide whether to treat the TS-related symptoms. Counselling and behavioural modification may be sufficient for those with mild symptoms. Medications, however, may be considered when symptoms begin to interfere with peer relationships, social interactions, academic or job performance, or with activities of daily living. Therapy must be individualised and the most troublesome symptoms should be targeted first. Antidopaminergic agents are clearly the most effective drugs in the treatment of tics. Although haloperidol and pimozide are the only drugs currently approved by the FDA for the treatment of TS, other dopamine receptor-blocking drugs and tetrabenazine, a dopamine depleting drug, as well as botulinum toxin injections, have been used to treat tics associated with TS. Carefully designed, comparative, longitudinal trials assessing the efficacy and adverse-effect profiles of these drugs, including tardive dyskinesia, are lacking. Selective serotonin reuptake inhibitors are recommended for the treatment of obsessive-compulsive behaviour: a common comorbidity. Psychostimulants, such as methylphenidate, are the treatment of choice for attention deficit hyperactivity disorder. Even though these drugs may transiently increase tics, this does not necessarily constitute a definite contraindication to the use of these drugs in patients with TS. Here, existing and emerging medical treatments in patients with tics and comorbid behavioural disorders associated with TS are reviewed.

Selenium supplementation may increase the efficacy of cetuximab in metastatic colorectal cancer patients.

Recently, cyclooxygenase-2 (COX-2) inhibitor therapy has emerged as a possible new approach to the prevention and treatment of colorectal cancer (CRC). The COX enzymes (COX-1 and COX-2) are key enzymes of prostaglandin (PG) biosynthesis and are overexpressed in approximately 80% of human CRCs. Presumably, bioactive lipid products of COX, such as PGE(2), are responsible for some of the pro-neoplastic effects mediated by this enzyme. The early effects of COX-2-derived PGE(2) are in part mediated by the epidermal growth factor receptor (EGFR). Selenomethionine decreases COX-2 protein and PGE(2) levels. Cetuximab is a chimeric IgG1 monoclonal antibody that binds to EGFR with high specificity thus blocking ligand-induced phosphorylation of EGFR. Cetuximab has clinically significant activity when given alone or in combination with irinotecan in patients with irinotecan-refractory CRC. We suggest that selenium supplementation by decreasing the COX-2 protein and PGE-2 levels in cancer cells may increase efficacy of cetuximab in advanced CRC patients.