Efficacy of flecainide,sotalol, and verapamil in the treatment of right ventricular tachycardia in patients without overt cardiac abnormality

Objective—A comparison of the efficacy of verapamil, sotalol, and flecainide to suppress right ventricular tachycardia (VT) in patients with a clinically normal heart.Design—Patients underwent treatment serially with verapamil (360 mg daily), sotalol (240 or 320 mg daily), and flecainide (200 or 300 mg daily), (the larger dose was for patients heavier than 80 kg) to suppress tachycardia. Each drug was given orally for five half lives before testing.Patients—23 patients with right VT associated with a clinically normal heart were studied.Outcome measures—The effects of drug treatment were examined by the number of ventricular events on 24 hour Holter monitoring, and the ability of tachycardia to be induced by treadmill exercise testing (Bruce protocol) and programmed ventricular stimulation (Wellens protocol), compared with drug free baseline tests.Setting—Patients were studied in a tertiary referral centre.Results—All three drugs suppressed ventricular salvos (>3, <5 consecutive ventricular premature contractions) (p < 0·01) and VT (p < 0·05) on Holter monitoring and did not differ statistically in effect. Exercise induced VT was also suppressed by all three drugs (p < 0·01), and of these sotalol was the most effective although this was not statistically significant (14/23 inducible when drug free, 4/23 on flecainide, 2/23 on sotalol, 5/23 on verapamil). Sustained and nonsustained VT induced by programmed stimulation was also suppressed by the three drugs (p < 0·01) and again sotalol was the best of these though the differences did not achieve statistical significance (17/23 inducible when drug free, 4/17 on flecainide, 2/17 on sotalol, and 6/17 on verapamil). Proarrhythmic effects of drugs were found in a few patients. There was no difference in the efficacy of the drugs in patients with histological abnormalities of the myocardium when compared with those of normal histology.Conclusions—Ventricular tachycardia associated with a clinically normal heart can be suppressed by flecainide, sotalol, or verapamil. In individual patients sotalol was the most frequently effective drug (effective in >89% of patients) and is a suitable choice for first line treatment.     

Inhibition of chronic relapsing experimental allergic encephalomyelitis in the Biozzi AB/H mouse

Chronic relapsing experimental allergic encephalomyelitis (CREAE) can be reproducibly induced in Biozzi AB/H mice following injection of spinal cord homogenate (SCH) emulsified in complete Freund's adjuvant (CFA). Active clinical disease is associated with mononuclear cell infiltration of the central nervous system (CNS), mainly the spinal cord. Whole brain homogenate (BH), however, failed to induce clinical or histological disease. In contrast, substituting sciatic nerve homogenate in the inoculum induced experimental allergic neuritis (EAN). Clinical disease was manifest earlier (13.1 +/- 0.3 days) than CREAE (16.2 +/- 1.4) and was accompanied by mononuclear infiltration of the peripheral nervous system (PNS). In comparison to CREAE induction, pretreating mice with SCH or BH in incomplete Freund's adjuvant (IFA) suppressed the development of SCH-induced disease. The BH was more tolerogenic than the SCH and this hyporesponsiveness was CNS antigen-specific as PNS tissue failed to inhibit the course of CREAE. Tolerance induced by pretreatment with SCH or BH in IFA was reversed by a single injection of 200 mg/kg cyclophosphamide, 2 days prior to CREAE induction. This suggests that IFA-induced hyporesponsiveness is actively regulated, possibly via the action of suppressor cells. In addition, treatment with neuroantigens in IFA appears to be mainly afferent acting as it serves to prevent initial disease induction. This treatment after immunization for CREAE, however, fails to prevent disease progression. Furthermore, treatment with CNS antigens emulsified in IFA during the post-acute remission stage appeared to synchronize and induce (32 +/- 1 days) the onset of clinical relapse, compared with untreated controls (41 +/- 5 days). This indicates that such IFA treatment has minimal value in controlling an ongoing immune disease of the CNS.     

Essential fatty acid deficiency in surgical patients.

Parenteral nutrition may protect patients unable to eat from malnutrition almost indefinitely. If fat is not also given EFAD will occur. This outlines a prospective study of 28 surgical patients on total intravenous fat-free nutrition to determine the developmental course of EFAD and the response to therapy. Twenty-eight patients ranging from newborn to 66 years receiving parenteral nutrition without fat had regular determinations of the composition of total plasma fatty acids and the triene/tetraene ratio using gas liquid chromatography. Physical signs of EFAD were looked for also. Patients found to have evidence of EFAD were treated with 10% Intralipid. Topical safflower oil was used in three infants. Total plasma fatty acid composition was restudied following therapy. In general, infants on fat-free intravenous nutrition developed biochemical EFAD within two weeks, but dermatitis took longer to become evident. Older individuals took over four weeks to develop a diagnostic triene/tetraene ratio (greater than 0.4; range 0.4 to 3.75). Therapeutic correction of biochemical EFAD took 7 to 10 days but dermatitis took longer to correct. Cutaneous application of safflower oil alleviated the cutaneous manifestations but did not correct the triene/tetraene ratio of total plasma fatty acids. These studies indicate that surgical patients who are unable to eat for two to four weeks, depending upon age and expected fat stores, should receive fat as a part of their intravenous regimen.     

Isolation of chlamydiae in untreated and Cytochalasin B treated McCoy cells.

A comparison was made between untreated McCoy cells and McCoy cells treated with Cytochalasin B for the isolation of chlamydiae of subgroup A. Chlamydiae were isolated in both cell systems from 125 specimens, whereas six agents were isolated only in untreated cultures and seven agents were isolated only in Cytochalasin B treated cultures.     

Chlorpromazine--a specific effect on breathlessness?

Previous work has left unresolved questions on whether promethazine reduces the sensation of breathlessness. This study was designed to provide a definitive answer and to determine the contributions from promethazine's major pharmacological actions. Twelve healthy subjects participated in a double-blind, within-subject comparison of promethazine and placebo each given acutely by mouth. Breathlessness was assessed with visual analogue scales during a progressive exercise test and was related to minute ventilation. Promethazine had no significant effect on breathlessness nor on the relationship between breathlessness and ventilation. The role of histamine-antagonism was investigated in a subgroup of the subjects by administration of mebhydrolin. No effect on breathlessness was detected. In contrast, the standard phenothiazine, chlorpromazine, caused a marked and statistically significant reduction in breathlessness without affecting ventilation and without causing detectable sedation. This unexpected finding merits further study in patients and is discussed with reference to the role of chlorpromazine as a constituent of Brompton's Mixture.