ABSTRACT
In this paper we propose a discrete in continuous mathematical model for the morphogenesis of the posterior lateral line system in zebrafish. Our model follows closely the results obtained in recent biological experiments. We rely on a hybrid description: discrete for the cellular level and continuous for the molecular level. We prove the existence of steady solutions consistent with the formation of particular biological structure, the neuromasts. Dynamical numerical simulations are performed to show the behavior of the model and its qualitative and quantitative accuracy to describe the evolution of the cell aggregate.
Subject(s)
Lateral Line System/embryology , Models, Biological , Zebrafish/embryology , Animals , Cell Aggregation , Cell Movement , Computational Biology , Computer Simulation , Fibroblast Growth Factors/physiology , Lateral Line System/cytology , Lateral Line System/physiology , Mathematical Concepts , Morphogenesis , Receptors, Fibroblast Growth Factor/physiology , Zebrafish/physiology , Zebrafish Proteins/physiologyABSTRACT
PURPOSE: Capecitabine and oxaliplatin are both active anticancer agents in the treatment of patients with advanced colorectal cancer (ACRC). The aim of this dose-finding trial was to determine the maximum-tolerated dose (MTD), the dose-limiting toxicities (DLTs) and the activity of the combination in patients with advanced colorectal cancer. PATIENTS AND METHODS: Twenty-five chemotherapy-pretreated patients received the combination of capecitabine and oxaliplatin. Capecitabine was administered orally twice a day continuously for 14 days in doses ranging from 1,650 to 2,500 mg/m2/d, and oxaliplatin was administered as a two-hour infusion on day 1 using dose, ranges from 100 to 130 mg/m2 repeated every three weeks. RESULTS: Twenty-five patients were assessable for toxicity, and DLTs were diarrhea (grade > or = 3: 27%) and stomatitis (grade > or = 3: 9%) at dose level VI. Dose level V (capecitabine 2500 mg/m2 and oxaliplatin 120 mg/m2) was found to be the MTD. Hematological toxicity was minimal, overall neurotoxicity (grade 1-4) was 27% with 1% grade 3-4. A global response rate was 17% (95% confidence interval (95% CI): 2%-32%) and the median overall survival was 12 months. CONCLUSION: The recommended dose for further phase II studies is capecitabine 2,500 mg/m2/d with intermittent schedule and oxaliplatin 120 mg/m2 every three weeks. The toxicities were mainly gastrointestinal: diarrhea, stomatitis and vomiting. This combination should be studied in phase II trials in advanced colorectal.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Deoxycytidine/analogs & derivatives , Adenocarcinoma/pathology , Adult , Aged , Capecitabine , Colorectal Neoplasms/pathology , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Diarrhea/chemically induced , Dose-Response Relationship, Drug , Drug Evaluation , Female , Fluorouracil/analogs & derivatives , Humans , Male , Maximum Tolerated Dose , Middle Aged , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Oxaliplatin , Safety , Survival RateABSTRACT
One hundred and eighteen patients with neurasthenia, as defined by ICD 10 (International Classification of Diseases), participated in a randomised, double-blind, placebo-controlled trial of pivagabine (4-[(2,2-dimethyl-1-oxopropyl)amino]butanoic acid, CAS 69542-93-4, Tonerg). Pivagabine 1800 mg/d was administered orally for four weeks. At the end of the trial, active medication was significantly superior to placebo on the Clinical Global Impression (CGI) improvement of illness scale. In addition, pivagabine treatment reduced the physical and mental fatigability of patients, and increased their sense of well-being.
Subject(s)
Neurasthenia/drug therapy , Psychotropic Drugs/therapeutic use , gamma-Aminobutyric Acid/analogs & derivatives , Adolescent , Adult , Aged , Double-Blind Method , Female , Humans , Male , Middle Aged , Neurasthenia/psychology , Psychiatric Status Rating Scales , Psychotropic Drugs/adverse effects , gamma-Aminobutyric Acid/adverse effects , gamma-Aminobutyric Acid/therapeutic useABSTRACT
A double-blind study was performed to evaluate carbamazepine for the prophylaxis of benzodiazepine withdrawal syndrome in elderly patients--a controversial subject despite the extensive use of such drugs in old age. Thirty-six outpatients aged > or = 60 yrs suffering from general anxiety disorders and benzodiazepine abuse underwent gradual discontinuation of benzodiazepine therapy in two groups, one treated with carbamazepine and one with placebo. The carbamazepine-treated group demonstrated a lower incidence of withdrawal symptoms rated according to the Physician Withdrawal Check List (p < 0.01), better results with the Hopkins Symptom Check List (Covi cluster, p < 0.01) and a more markedly reduced score with the Hamilton Rating Scale for Anxiety (p < 0.05). Only 3 out of 18 patients in said group complained of side effects attributable to carbamazepine, which disappeared at lower dosages.
Subject(s)
Benzodiazepines/adverse effects , Carbamazepine/therapeutic use , Placebos/therapeutic use , Substance Withdrawal Syndrome/drug therapy , Aged , Anxiety Disorders/diagnosis , Anxiety Disorders/etiology , Carbamazepine/administration & dosage , Female , Humans , Male , Substance Withdrawal Syndrome/psychologyABSTRACT
The authors retrospectively examined the clinical outcome (after 1, 2 and 5 years of beginning the therapeutic protocols) for 16 rapid-cycling bipolar affective disorder patients given either lithium alone or lithium plus carbamazepine. The results suggest that both therapeutic protocols have been safe and clinically effective. However, improvement was observed earlier in the patients given lithium and carbamazepine.
Subject(s)
Bipolar Disorder/drug therapy , Carbamazepine/administration & dosage , Lithium/administration & dosage , Adult , Bipolar Disorder/psychology , Drug Therapy, Combination , Female , Humans , Longitudinal Studies , Male , Middle Aged , Psychiatric Status Rating Scales , Retrospective StudiesABSTRACT
Compliance to the prescription of anticholinergic drugs in 274 consecutive schizophrenic outpatients has been assessed retrospectively from their clinical records. Ten point four percent of the sample (22 patients) took these drugs in amounts greater than those prescribed. Some possible explanations of this excessive use are discussed.
