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A DeLuca

Publications and source records attributed to A DeLuca.

5 recordsLinked to original sources

The different use dependences of tocainide and benzocaine are correlated with different effects on sodium channel inactivation.

To study the mechanism of use dependence, we investigated the influence of 0.5 mM tocainide on the amplitude of sodium currents elicited by membrane depolarizations with standard test pulses in voltage-clamped human myoballs. For comparison, the experiments were also conducted with 1 mM benzocaine, a drug with almost no use dependence. These concentrations were so chosen that without stimulation and at a holding potential of -135 mV, either drug blocked about 50% of the channels (tonic block). With repetitive stimulation at 1 Hz, tocainide blocked about 75% of the channels that had remained open in the rested state (phasic block), while benzocaine had little such effect. The potential dependence of steady-state inactivation (h infinity curves) of the sodium channels in these myoballs depended on the duration of the prepotential indicating that they possess at least two states of inactivation: fast and intermediate. The two drugs differed in their effects on these two states. Benzocaine always produced a left-shift of the h infinity curve, no matter whether the duration of the conditioning pulse was short (8 ms) or long (512 ms) indicating that it can bind when the channel is in the state of fast inactivation. Tocainide shifted the h infinity curve only with long prepulses, i.e. when the sodium channels were in the state of intermediate inactivation. The recovery from inactivation, a process governed by two time constants in the absence of drugs, was also differently influenced by the two drugs. In the presence of tocainide, the channels mainly recovered with the slow time constant and this time constant was significantly increased, whereas benzocaine did not substantially modify this biphasic process.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzocaine

Pulmonary edema due to extreme left atrial compression.

Pulmonary edema is a common concomitant of valvular heart disease and ventricular dysfunction. In addition, left atrial dysfunction due to thrombus, myxoma, or cor triatriatum can produce the same clinical picture. We encountered a patient with intractable pulmonary edema secondary to obliteration of the left atrial cavity by an extrinsically compressing lung tumor. We believe extrinsic compression of the left atrium caused impaired left atrial filling, leading to pulmonary venous hypertension and pulmonary edema.

Atrial Function, Left

Tumor induction following intraoperative radiotherapy: late results of the National Cancer Institute canine trials.

Intraoperative radiotherapy has been employed in human cancer research for over a decade. Since 1979, trials to assess the acute and late toxicity of IORT have been carried out at the National Cancer Institute in an adult dog model in an attempt to establish dose tolerance guidelines for a variety of organs. Of the 170 animals entered on 12 studies with a minimum follow-up of 2 years, 148 dogs received IORT; 22 control animals received only surgery. Animals were sacrificed at designated intervals following IORT, usually at 1, 6, 12, 24, and 60 month intervals. 102 of 148 irradiated dogs were sacrificed less than 24 months; 46 dogs were followed greater than or equal to 24 months after IORT. To date, 34 of the 46 animals have been sacrificed; the 12 remaining animals are to be followed to 5 years. These 12 animals have minimum follow-up of 30 months. In the irradiated group followed for greater than or equal to 24 months, 10 tumors have arisen in 9 animals. One animal developed an incidental spontaneous breast carcinoma outside the IORT port, discovered only at scheduled post-mortem exam. The remaining nine tumors arose within IORT ports. Two tumors were benign neural tumors--a neuroma and a neurofibroma. One animal had a "collision" tumor comprised of grade I chondrosarcoma adjacent to grade III osteosarcoma arising in lumbar vertebrae. Two other grade III osteosarcomas, one grade III fibrosarcoma, and one grade III malignant fibrous histiocytoma arose in retroperitoneal/paravertebral sites. An embryonal rhabdomyosarcoma (sarcoma botryoides) arose within the irradiated urinary bladder of one animal. No sham irradiated controls nor IORT animals sacrificed less than 24 months have developed any spontaneous or radiation-induced tumors. The time range of diagnoses of tumors was 24-58 months (median 40 months). The IORT dose range associated with tumor development was 20-35 Gy (median 30 Gy). The carcinogenesis capability of single fraction, high dose radiation in animals is discussed, as are the implications of these data for continued research and clinical usage of IORT in the treatment of humans.

Animals

Pulmonary diffusing capacity in left ventricular dysfunction.

The purpose of this study was to determine whether there are any consistent spirometric or Dsb findings in patients with LV dysfunction characterized by a clinical diagnosis of CHF and an EF less than 40 percent. We performed spirometry and Dsb in 34 patients, and found that EF correlated only with Dsb. When we separated the patients into those with rales and those without, Dsb correlated strongly with EF only in those with rales. There was no correlation with other spirometric values. Mean Dsb percent predicted was significantly lower in patients with rales despite similar mean EF. Only two of 23 patients without rales had a reduced Dsb while only one of 11 with rales had a normal Dsb. We conclude that Dsb is a good predictor of clinically evident heart failure. When rales are absent, Dsb should be normal in patients with LV dysfunction; when present, Dsb will be diminished in proportion to the EF.

Aged

Enantiomers of clofibric acid analogs have opposite actions on rat skeletal muscle chloride channels.

The S-(-) isomers of a series of clofibric acid analogs produced only a block of chloride conductance of rat skeletal muscle fibers with increasing concentrations until block was nearly complete. The R-(+) isomers, on the other hand, at low concentrations increased chloride conductance by as much as 9% to 39% and at higher concentrations decreased chloride conductance, but never by more than 27% of the control value. The actions of the enantiomeric pairs to either produce or inhibit myotonic excitability paralleled their ability to block or increase chloride conductance, respectively.

Animals