ABSTRACT
OBJECTIVE: Two pilot studies were conducted to evaluate safety, tolerability, and efficacy of two doses of Protiramer (TV-5010) in patients with relapsing-remitting multiple sclerosis. BACKGROUND: Both glatiramer acetate and TV-5010 are synthetic copolymers comprised the same four amino acids in a defined molar ratio. TV-5010 has higher average molecular weight than Glatiramer acetate and might be hypothesized that glatiramoids with higher molecular weight might be more immunoreactive than lower molecular weight peptides, thus increasing therapeutic potential and allowing for less frequent dosing. METHODS: In the two separate studies, after a 10 week pretreatment period, TV-5010 was given subcutaneously once weekly at 15 mg and 30 mg for 36 weeks. The primary end point was a reduction in the number of magnetic resonance imaging active lesions (i.e., T1-weigthed gadolinium-enhancing and new T2-weighted lesions) between the pretreatment period and the end of study. RESULTS: Both TV-5010 doses were generally well tolerated. The treatment with TV-5010 at a dose of 15 mg/wk did not show any significant effect. In contrast, in patients treated with at a dose of 30 mg/wk, a significant reduction in the mean number of gadolinium-enhancing (-58.8%; P = 0.0013) and new T2-W (-50%; P = 0.0002) lesions was observed. However, a large decrease in the mean number of both gadolinium-enhancing (-55%) and new T2-W (-40%) lesions during the pretreatment period made difficult the interpretation of the efficacy assessments. CONCLUSIONS: Further studies are needed to confirm these preliminary data on safety and efficacy of TV-5010 at a weekly dose of 30 mg.
Subject(s)
Immunosuppressive Agents/administration & dosage , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Peptides/administration & dosage , Adult , Chemistry, Pharmaceutical , Dose-Response Relationship, Drug , Female , Glatiramer Acetate , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/chemistry , Injections, Subcutaneous , Male , Molecular Weight , Peptides/adverse effects , Peptides/chemistry , Pilot Projects , Treatment OutcomeABSTRACT
Stroke mortality is extremely high in Central-Eastern European countries. The high rate of risk factors and differences in health care services might be among the factors resulting in high stroke morbidity and mortality in this region. As only few prospectively collected information are available from this region, we decided to evaluate some characteristics of stroke services in neurological departments of a Romanian, a Ukrainian and a Hungarian city in the framework of the Mures-Uzhgorod-Debrecen comparative epidemiological study. We registered demographic data, the absence or presence of the most important risk factors, and clinical signs on admission and at discharge. We recorded the application of various diagnostic methods, stroke treatment and recommendations for secondary prevention. Follow-up is planned after 30 days and after 1 year. The paper summarizes the methodology of this prospective epidemiological study of stroke patients hospitalized in neurological departments in Târgu Mures, Uzhgorod and Debrecen, three Central-Eastern European cities in Romania, Ukraine and Hungary, respectively.
Subject(s)
Hospital Departments/statistics & numerical data , Stroke/epidemiology , Stroke/therapy , Follow-Up Studies , Humans , Hungary/epidemiology , Observer Variation , Prospective Studies , Risk Factors , Romania/epidemiology , Ukraine/epidemiologySubject(s)
Subarachnoid Hemorrhage/physiopathology , Adolescent , Adult , Aged , Aged, 80 and over , Aging , Alcoholism/complications , Anticoagulants/therapeutic use , Cerebral Angiography , Child , Electroencephalography , Female , Humans , Hypertension/complications , Male , Middle Aged , Ophthalmoscopy , Risk Factors , Sex Characteristics , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/diagnosisSubject(s)
Cerebrovascular Disorders/drug therapy , Prostaglandins/therapeutic use , Arteriosclerosis/drug therapy , Brain Ischemia/drug therapy , Cardiovascular Physiological Phenomena , Constriction, Pathologic/drug therapy , Epoprostenol/physiology , Humans , Migraine Disorders/drug therapy , Prostaglandin Antagonists/therapeutic use , Prostaglandins/physiology , Thromboxane A2/physiologySubject(s)
Intracranial Arteriosclerosis/diagnosis , Adaptation, Psychological/physiology , Arteriosclerosis/metabolism , Arteriosclerosis/pathology , Brain Ischemia/diagnosis , Brain Ischemia/etiology , Brain Ischemia/psychology , Cerebrovascular Circulation , Cholesterol/blood , Dementia/diagnosis , Dementia/etiology , Depressive Disorder/diagnosis , Depressive Disorder/etiology , Diagnosis, Differential , Female , Humans , Intracranial Arteriosclerosis/etiology , Intracranial Arteriosclerosis/psychology , Lipids/blood , Male , Middle Aged , Mood Disorders/diagnosis , Mood Disorders/etiology , Neurologic Examination , Psychopathology , Psychotic Disorders/diagnosis , Psychotic Disorders/etiology , Syndrome , Terminology as TopicSubject(s)
Cerebrovascular Disorders/diagnosis , Electrocardiography , Acute Disease , Aged , Arrhythmias, Cardiac/diagnosis , Cerebral Hemorrhage/diagnosis , Cerebrovascular Disorders/pathology , Female , Humans , Intracranial Embolism and Thrombosis/diagnosis , Male , Subarachnoid Hemorrhage/diagnosisSubject(s)
Cerebral Infarction/physiopathology , Computers , Electroencephalography/methods , Humans , Middle AgedABSTRACT
Starting from the assumption that binding of chlorpromazine to the erythrocyte membrane might influence th rheology of these cells, the authors studied erythrocyte aggregability and deformability by means of a filtrability test in 42 neurotics and 16 patients with personality disorders, all males, aged 20 to 27 years, clinically healthy from the somatic view point. Determinations were carried out before and 30 min after a single i.m. dose of 1 mg/kg b.w. chlorpromazine (14 patients) and before and after a 5-day oral treatment with 3 mg/day haloperidol (11 patients) or 75 mg/day chlorpromazine (33 patients). Chlorpromazine induced a significant decrease of erythrocyte aggregability after 5 days of oral treatment (p less than 0.02) the effect being more marked in the patients with relatively high initial values (p less than 0.01). The mechanism of this phenomenon and its possible implications of ESR determination and in the therapy of occlusive vascular diseases are discussed.
