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Biomedical subjects

R M Thomas

Publications and source records attributed to R M Thomas.

95 records · Page 6Linked to original sources

Therapeutic irradiation of the central nervous system using intrathecal 90Y--DTA.

The erdication of established neuroleukaemia is often difficult, and with subsequent relapses even harder. The use of an intrathecally-injected beta emitting isotope has the advantage of preserving the bone-marrow of the vertebral column and cranium whislt irradiating the meninges. The value of intrathecal 90Y-DTPA(diethylene-triamine penta-acetic acid) has been investigated in nine patients with neuroleukaemia or CNS involvement in malignant lymphoma. Measurements of retention of the isotope in the whole body, spinal, and intracranial subarachnoid spaces have been made, together with blood levels, and are reported. The clinical results are presented. In three out of five evaluable patients 90Y-DTPA failed to maintain a chemotherapy-induced CNS remission and in two out of two evaluable patients malignant cells were not dispersed from the CNS with a single intrathecal injection of 90Y-DTA. It is concluded, therefore, that with this agent and the doses used no useful clinical result is gained.

Adolescent↗

Subtypes of dorsal root ganglion neurons based on different inward currents as measured by whole-cell voltage clamp.

Electrophysiological and pharmacological properties distinguished subtypes of adult mammalian dorsal root ganglion neurons (DRGn) in monolayer dissociated cell culture. By analogy of action potential waveform and duration, neurons with short duration (SDn) and long duration (LDn) action potentials resembled functionally distinct subtypes of DRGn in intact ganglia. Patch clamp and conventional intracellular recording techniques were combined here to elucidate differences in the ionic basis of excitability of subtypes of DRGn in vitro. Both SDn and LDn were quiescent at the resting potential. Action potentials of SDn were brief (less than 2 msec), sensitive to tetrodotoxin (TTX, 5-10 nM), exhibited damped firing during long depolarizations, and did not respond to algesic agents applied by pressure ejection. Action potentials of LDn were 2-6 msec in duration, persisted in 30 microM TTX, and fired repetitively during depolarizing current pulses or exposure to algesic agents (e.g., capsaicin, histamine and bradykinin). Whole-cell recordings from freshly dissociated neurons revealed two inward sodium currents (INa; variable with changes in sodium but not calcium concentration in the superfusate) in various proportions: a rapidly activating and inactivating, TTX-sensitive current; and, a slower, TTX (30 microM)-resistant INa. Large neurons, presumable SDn, had predominantly TTX-sensitive current and little TTX-resistant current. The predominant inward current of small neurons, presumably LDn, was TTX-resistant with a smaller TTX-sensitive component. By analogy to findings from intact ganglia, these results suggest that fundamentally different ionic currents controlling excitability of subtypes of DRGn in vitro may contribute to functional differences between subtypes of neurons in situ.

Action Potentials↗

Influence of CCK and bombesin on ACTH and cortisol secretion in the conscious dog.

Bombesin and cholecystokinin (CCK) have a variety of similar actions. Previous investigations have demonstrated that IP injections of bombesin and CCK-33 increased corticosterone secretion in conscious, freely-moving, fed rats. In this study bombesin or CCk-8 was administered by continuous, intravenous infusion to conscious, awake, fasted, mongrel dogs. Following a 30-40 minute control infusion, a progressively-increasing, stepwise infusion of either bombesin (0.1, 1.0 and 2.0 micrograms/kg-hr) or CCK-8 (62.5, 125, and 250 ng/kg-hr) was administered. Each drug dose was infused for 40-45 minutes and blood samples were drawn at 20-22.5 minutes intervals. Bombesin caused significant, dose-dependent increases in plasma cortisol (286 +/- 39% of control) and plasma ACTH (176 +/- 33% of control). CCK-8 had no consistent effect on either cortisol or ACTH secretion. Whether the lack of effect of CCK-8 in dogs, as compared to rats, is due to species variations or to the differing experimental designs is unknown.

Adrenocorticotropic Hormone↗