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Biomedical subjects

R D Kaufman

Publications and source records attributed to R D Kaufman.

9 recordsLinked to original sources
PubMed1990

The effect of total parenteral nutrition and morphine on ventilation.

Total parenteral nutrition (TPN), specifically amino acid infusions, has been shown to increase the ventilatory response to inhaled CO2. The hypothesis tested was that morphine sulfate (known to depress ventilatory CO2 responsiveness) would diminish the augmented ventilatory CO2 response in patients receiving TPN. The influence of morphine on hyperoxic hypercapnic ventilatory response (assessed by the Read rebreathing technique) was therefore examined in four otherwise healthy subjects who were receiving TPN at home for long-standing nutritional support secondary to malabsorption syndrome (short-bowel syndrome), and in a control group of four healthy subjects who were not receiving TPN. The slope and intercept of the CO2 response was estimated by linear regression on the relationship between ventilation (VE) and end-tidal PCO2 (PETCO2). Administration of morphine in the non-TPN group elicited the expected decrease in the VE-PETCO2 slope. In contrast, morphine administration was associated with an increase in the VE-PETCO2 slope in the TPN group. While this investigation does not provide a direct indication of the mechanisms underlying the augmenting action of morphine on the ventilatory response to CO2 in subjects receiving TPN, it does suggest that patients on TPN who demonstrate no impairment of ventilatory control may be given normal doses of morphine sulphate (ie, as for pain control or preoperative medication) with no increased concern for an adverse ventilatory outcome.

Adult↗
PubMed1979

Relative potencies and durations of action with respect to respiratory depression of intravenous meperidine, fentanyl and alphaprodine in man.

Fentanyl, 0.7 and 1.4 microgram/kg, alphaprodine, 0.135 and 0.270 mg/kg meperidine, 0.564 and 1.127 mg/kg, and placebo were administered intravenously over 2.6 min by infusion to five healthy adult males. The crossover study was of incomplete Latin square design with at least 1 week between administrations of each study drug. The subjects breathed from a mixing chamber the gas composition of which was servo-controlled so as to produce CO2 ramps in the end-tidal gases. Each experiment was composed of: 1) control CO2 ramps, 2) a 25-min isocarbic run during which the drug was infused and 3) CO2 ramps at half-hour intervals for 3 hr postinfusion. The 20-liter intercept (the PETCO2 at which ventilation was 20 liters/min) was used as the measure of respiratory drive; the change in 20-liter intercept measured drug effect. The potency ratios at peak effect were: fentanyl/meperidine, 679; alphaprodine/meperidine, 3.68; fentanyl/alphaprodine, 179. With the area under the time-effect curves, the potency ratios of mean effect were: fentanyl/meperidine, 45c; alphaprodine/meperidine, 3.00; fentanyl/alphaprodine, 141. Thus, both fentanyl and alphaprodine are shorter-acting than meperidine, and fentanyl is shorter-acting than alphaprodine. The time-effect curves were fitted to linear and mono- and bi-exponential models. The time constants were compatible with the above relative durations of action.

Adult↗
PubMed1978

Effect of hypercapnia on hypoxic ventilatory drive in carotid body-resected man.

Steplike end-tidal hypoxic drives (PETCO2 = 53 Torr) lasting for 5 min were generated in a group of normal subjects and a group of carotid body-resected subjects when end-tidal CO2 was maintained constant under eucapnic (PETCO2 = 39 Torr) and hypercapnic (PETCO2 = 49 Torr) conditions. The hypoxic ventilatory response of the normal subjects was prompt and significant in eucapnia and was enhanced in the hypercapnic state, evidencing CO2-O2 interaction. In contrast, the carotid body-resected subjects did not respond to eucapnic hypoxia but did demonstrate a small but significant ventilatory response to hypoxia against the hypercapnic background. This suggests that the aortic bodies in man may contribute a small component of the hypoxic ventilatory drive under hypercapnic conditions, although the possibility of neuromalike ending regeneration cannot be excluded.

Adult↗
PubMed1977

Biophysical mechanisms of anesthetic action: historical perspective and review of current concepts.

The large number and diversity of anesthetic agents were evident to investigators 80 years ago, and suggested a physicochemical theory of anesthesia. Meyer and Overton were the first to offer a quantitative relationship between a physicochemical property and potency of anesthetic agents. They also focused attention on the lipid phase as the site of anesthetic action. Ferguson realized that the concentration of an agent at its site of action bears a generally unknown relation to the concentration in the external phase. However, at equilibrium the activity of an agent is the same in every phase, motivating Ferguson to suggest that activities rather than concentrations be used as indices of dosage. The critical-volume theory resulted from modification of the Meyer-Overton theory to include the molal volume of the anesthetic. The allowance for molal volume resulted initially from an attempt further to regularize the experimental data. The concept of a critical-volume fraction of anesthetic being necessary for narcosis was discussed in most detail by Mullins. Subsequently, the concept of the effect of the anesthetic has changed from filling of free space to expansion and fluidization of the membrane. The ability of pressure to cause excitant phenomena and antagonize anesthetics is predictable from the critical-volume theory and is therefore highly significant evidence. K. W. Miller and associates are perhaps most prominent in the recent quantification and formalization of the critical-volume theory and HPNS. The existence of a separate convulsant site(s) is suggested by the demonstration of significantly different compressibilities associated with anesthesia and convulsions. Work corroborating a separate convulsant site involved measurement of the partial molal volumes of a series of related convulsant and anesthetic ethers and calculation of each compound's solubility parameter. Multiple convulsant sites may exist, and these two methods may not have accessed the same site. Understanding the anesthetic-convulsant duality will have important practical application to deepwater diving, and may well offer important insight into the neurophysiologic and electrophysiologic effects of anesthetics. The application of ESR and NMR allows investigation at the molecular level of effects of anesthetics on biological and model membranes. Magnetic resonance techniques have generally supported the concept of membrane fluidization by anesthetics. Some investigators have recently attempted to displace the focus of attention from the lipid phase. However, the evidence is clearly against the aqueous-phase theory of Pauling and S.L. Miller. The microtubule theory of Allison and Nunn has not accumulated supporting evidence comparable to the lipid theories. Contradictory evidence makes any evaluation of this theory speculative. Additionally, the interspecies and intracellular variability of microtubules raises questions of the relevance of many studies...

Anesthesia, General↗
PubMed1975

Respiratory effects of lorazepam, pentobarbital, and pentazocine.

The respiratory effects of a new benzodiazepine, lorazepam, were compared to those of pentobarbital and pentazocine. Pentobarbital, 50 and 150 mg, produced respiratory depression, as did pentazocine, 30 mg intramuscularly. Lorazepam at 1.33 and 4 mg intramuscularly produced none.

Anti-Anxiety Agents↗