Search PubMed⌕ Search

Biomedical subjects

G J Blake

Publications and source records attributed to G J Blake.

41 records · Page 3Linked to original sources
PubMed1984

Augmented anti-acetylcholine receptor response following long-term penicillamine administration.

Because of the association of D-penicillamine (DP) therapy with myasthenia gravis, we have studied long-term DP treatment in five inbred strains of mice with doses comparable to those used in patients with rheumatoid arthritis. No clinical weakness or anti-acetylcholine receptor (AChR) antibody developed with up to 6 months of treatment, but augmented responses did occur to challenge with purified AChR in adjuvant. Anti-AChR antibody titers in C57BL/6 and C3H/He mice were significantly higher after challenge with AChR in DP-treated than in control mice. Augmented anti-AChR titers were not seen in strain A mice, but after 6 months of DP treatment increased susceptibility developed to the induction of experimental autoimmune myasthenia gravis. Nine weeks after challenge with purified AChR, 10 of 11 mice developed clinical weakness, leading to death in 6. Results of edrophonium testing were positive in 5 of 6 mice, and electrophysiological abnormalities were demonstrated in 3 of the surviving mice. Long-term DP treatment is associated with augmented anti-AChR antibody responses in C3H/He and C57BL/6 mice, and increased susceptibility to experimental autoimmune myasthenia gravis in strain A mice.

Animals↗
PubMed1984

Electrophysiologic substrate for ventricular tachycardia: correlation of properties in vivo and in vitro.

Cardiac electrophysiologic studies were performed in three control dogs and in nine dogs with previous (8 to 22 days) anterior myocardial infarction. During programmed stimulation, no control dog had more inducible ventricular fibrillation (VF) or tachycardia (VT), three dogs with infarcts had inducible VF and six had inducible VT. Recordings in vivo were made via a plaque electrode containing 10 bipolar electrodes (3.0 x 1.5 cm) placed on the epicardial surface of the anteroapical left ventricle. Subsequently, epicardial strips (2 mm thick) from beneath the plaque were prepared for studies in vitro. Electrogram durations were significantly greater in dogs with infarcts than in control dogs both in vivo (p less than .05) and in vitro (p less than .001). Electrogram amplitudes were significantly lower in dogs with VT in vivo (p less than .05) and in vitro (p less than .001). In control animals activation was continuous and most rapid in the direction of fiber orientation; there were areas of slow and/or discontinuous conduction in all dogs with infarcts. In one case, sustained reentrant beating in vitro was caused by functional unidirectional block and microreentry at a site of continuous electrical activity during VT in vivo. Reentrant beating in vitro persisted in 0.5 cc of isolated tissue. We conclude that broad low-amplitude electrograms in vivo and in vitro depict local areas of slow and/or discontinuous conduction, that the intrinsic asymmetry of cardiac activation due to fiber orientation is accentuated by infarction and may predispose to intraventricular reentry, and that intraventricular reentrant circuits that may be present on the epicardial surface may persist in a volume of myocardial tissue as small as 0.5 cc.

Animals↗
PubMed1983

Characterization of the train-of-four response in fast and slow muscles: effect of d-tubocurarine, pancuronium, and vecuronium.

The in vivo cat soleus and gastrocnemius muscles were used to compare isometric contraction strength and the train-of-four (T4) response (2 Hz for 2 s) of two muscle types (fast and slow) during onset of competitive neuromuscular blockade in order to determine the extent of the correlation between twitch depression and T4 fade. Prior to drug administration the muscles that were studied differed significantly in that the T4 ratio was 1.0 in the gastrocnemius and only 0.87 in the soleus. Three competitive neuromuscular-blocking agents were compared: d-tubocurarine, pancuronium, and vecuronium. d-Tubocurarine was found to produce a close correlation between the degrees of twitch strength depression and T4 for both muscles. However, these muscles demonstrated significantly different ED50 values (105 micrograms/kg for gastrocnemius, 150 micrograms/kg for soleus). Pancuronium also produced a similar relationship between twitch strength depression and T4 decrement for each muscle. In this case, however, there was little difference in their ED50 values for twitch depression (11.5 micrograms/kg for gastrocnemius, 13 micrograms/kg for soleus). The effects of vecuronium were quite different from the other two muscle relaxants. Although vecuronium produced a comparable correlation between twitch tension and T4 fade in fast muscle, no such relationship was found to exist in slow muscle. Even when the twitch strength was blocked to 18% of control, the soleus T4 response was depressed to only 75% of control. These results highlight major differences among competitive neuromuscular-blocking agents and suggest multiple sites of action.

Animals↗
PubMed1979

Differential selectivity of several barbiturates on experimental seizures and neurotoxicity in the mouse.

Six barbiturates with diverse time-action characteristics--thiopental, pentobarbital, butabarbital, phenobarbital, diphenylbarbiturate, and barbital--were evaluated for "anticonvulsant" and "neurotoxic" effects. For the former, the MES test, clonic seizures induced by pentylenetetrazol, 90 mg/kg, s.c., and maximal seizures produced by pentylenetetrazol, 200 mg/kg, s.c., were employed. For the latter, we used a rotorod technique. Time to peak activity in the MES test was employed as the time for other tests. Pentobarbital required at least neurotoxic doses to produce substantial "anticonvulsant" activity, its protective index ranging from 0.79 to 0.98 in the three tests. Among the drugs tested, phenobarbital and diphenylbarbiturate exhibited the most favorable protective indices, ranging from 2.71 to 3.41 for phenobarbital and from 3.85 to 5.0 for diphenylbarbiturate. Barbital, another drug with a prolonged duration of action, exhibited a range from 0.84 to 2.81. Although a prolonged duration of action is an important characteristic for antiepileptic activity, this property does not confer per se a favorable protective index.

Animals↗