Peter J. Cohen

Further studies of the anti-recall effect of lorazepam: A dose--time--effect relationship.

The time of onset and duration of tlie anti recall action of Iorazcpam were assessed under clinical conditions by measuring recall and rccognition of visual stimuli 24 hours after intravenous administration of Iorazepam. The visual stimuli were first presented 5–240 minutes after 2 mg and 5–360 minutes after 4 mg Iorazepam. Retrograde amnesia was not produced. Lorazepam, 2 mg produced a short anti-recall effect (enterograde amnesia) in 50 per cent of the cases with a latency of 30 minutes and a duration of less than half an hour. Duration and frequency of the anti-recall effect were greater after 4 mg while the latency was shorter. More than 70 per cent of the individuals tested were amnesia for the visual stimuli 15 minutes to 4 hours after 4 mg lorazepam. Sedation was satisfactory and long-lasting following both doses of lorazepam, but was not related to the antirecall effect.

Cerebral Circulation During General Anesthesia and Hyperventilation in Man

Studies of cerebral circulation and gaseous metabolism were performed in six healthy young volunteers during anesthesia induced with thiopental and maintained with nitrous oxide and d-tubocurarine. The blood thiopental level was very low when measurements were made, and intravenous d-tubocurarine has been shown not to affect cerebral flow or metabolism. Therefore 70 per cent nitrous oxide was probably the agent chiefly responsible for the changes observed. When Paco2 was normal, cerebral blood flow remained normal, but cerebral oxygen uptake decreased 23 per cent. About one third of this decrease was caused by a small decline in body temperature, with the remainder most likely owing to nitrous oxide. When mean arterial Pco2 was decreased to 18.3 mm. of mercury, cerebral blood flow was halved, and mean jugular venous Pco2 declined to 19.8 mm. of mercury, a level generally assumed to be associated with suboptimal cerebral oxygenation. However, cerebral metabolic rate for oxygen did not decrease further at this low Paco2.

Exercise with Anemia: The Role of the Left-Shifted or Right-Shifted Oxygen-Hemoglobin Equilibrium Curve

Abstract Two patients with similar degrees of anemia, one with a left-shifted and one with a right-shifted oxygen-hemoglobin equilibrium curve, were exercised on a bicycle ergometer. The patient wi...

CEREBRAL CARBOHYDRATE METABOLISM DURING HYPOCARBIA IN MAN: STUDIES DURING NITROUS OXIDE ANESTHESIA.

Brain carbohydrate metabolism was studied in 11 healthy male volunteers during anesthesia induced with intravenous thiopental (5 mg./kg.) and maintained with 70 per cent N2O-30 per cent O2 and d-tubocurarine. When arterial PCO2 (PaCO2) was normal, oxygen and glucose consumption were reduced approximately 25 per cent from the normal value in conscious man; but no change in the pattern of glucose utilization was noted. A reduction in PaCO2 below 20 mm. of mercury was accompanied by a decreased aerobic and an increased anaerobic utilization of glucose. Mild, readily reversible changes in the EEG pattern also occurred when PaCO2 was less than 20 mm. of mercury. Clinical implications of these changes are discussed. The validity of several indices of cerebral carbohydrate metabolism is considered.

CEREBRAL CIRCULATION OF MAN DURING HALOTHANE ANESTHESIA: EFFECTS OF HYPOCARBIA AND OF D-TUBOCURARINE.

Cerebral circulatory measurements were made in 13 young normal male volunteers anesthetized with 1.2 per cent halothane in oxygen. Studies were performed at normal and at low PaCO2 with intravenous d-tubocurarine and at low PaCO2 without d-tubocurarine. During halothane anesthesia the cerebral vasculature was shown to constrict when PaCO2 was lowered, a response similar to that which has been observed in awake man. Halothane in the concentration studied was demonstrated to be a mild cerebral vasodilator. d-Tubocurarine was shown not to affect either cerebral blood flow, cerebral vascular resistance, or cerebral oxygen consumption. The relation of cerebral blood flow to the more easily measured jugular venous PO2 is demonstrated and discussed.

CEREBRAL CARBOHYDRATE METABOLISM IN MAN DURING HALOTHANE ANESTHESIA: EFFECTS OF PACO2 ON SOME ASPECTS OF CARBOHYDRATE UTILIZATION.

Cerebral blood flow and carbohydrate utilization were measured in healthy adult male volunteers during anesthesia produced by 1.2 per cent halothane in oxygen during hypocarbia, normocarbia, and mild hypercarbia. Cerebral oxygen consumption was unaffected by the rate of cerebral blood flow but was diminished by approximately 15 per cent in the presence of a 1°C. fall in body temperature. Metabolic alterations induced by 1.2 per cent halothane were slight or absent. Increased anaerobic metabolism was not demonstrated when cerebral blood flow was diminished during hypocarbia. Slight alterations in the pathways of glucose and oxygen metabolism were shown to be produced by changes in PaCO2.

Hepatic dysfunction after isoflurane anesthesia.

Four members of the Anesthetic and Life Support Advisory Committee of the Food and Drug Administration assessed the contribution of isoflurane (Forane) to 45 instances of hepatic dysfunction after isoflurane anesthesia reported to the FDA for 1981-1984. For 29 (64%) of the cases, at least three members concluded that nonanesthetic causes (e.g., hypoxia, sepsis, viral infection) explained the hepatic injury. For 16 cases (36%), two or more members concluded that isoflurane might be one of several possible causes of the hepatic injury. In the latter cases, patients tended to be younger, had undergone anesthesia of shorter duration for operations outside the chest and abdomen, had developed symptoms later, had higher plasma transaminase values but lower bilirubin values, and had a lower incidence of eosinophilia, anemia, transfusions, and congestive heart failure. The committee concluded that current evidence does not indicate a reasonable likelihood of an association between the use of isoflurane and the occurrence of postoperative hepatic dysfunction.

The Use of Haloperidol for Treatment of Postoperative Nausea and Vomiting—A Double-blind Placebo-controlled Trial

Sixty-two postoperative patients were admitted to a double-blind study to compare the therapeutic effectiveness of a single intramuscular injection of 1 mg of haloperidol with that of a placebo for the relief of vomiting and nausea following surgical procedures. Significantly fewer patients continued to vomit or experience nausea in the haloperidol-treatment group than in the placebo-treatment group. No statistically or clinically significant change in vital signs occurred in the haloperidol-treatment group. No serious side effect occurred in either group.

The Effects of Forane and Fluroxene on Mitochondrial Respiration: Correlation with Lipid Solubility and In-vivo Potency

Rat liver mitochondria were exposed to various concentrations of Forane and fluroxene. Polarographic measurement of oxygen uptake during glutamate oxidation demonstrated dose-related reversible inhibition of state 3 respiration following treatment with each agent. In contrast, state 3 succinate oxidation remained unaffected, although irreversible loss of respiratory control followed exposure to high anesthetic concentrations. Thus, Forane and fluroxene interfere with glutamate oxidation by blocking electron transport at the NADH dehydrogenase locus in a fashion similar to other volatile anesthetics.Inhibition of state 3 glulamate oxidation by rat liver mitochondria has been demonstrated previously for halothane, diethyl ether, methoxyflurane and enfluranc. The concentrations of anesthetic necessary for 50 per cent inhibition of state 3 respiration (ID20) were calculated for all six agents and found to bear an inverse log-log relationship to lipid solubility. Potency in vitro (ID20) was directly related to potency in vivo (MAC). This relationship may reflect similar molecular mechanisms of action.

International Stem Cell Tourism and the Need for Effective Regulation: Part II: Developing Sound Oversight Measures and Effective Patient Support

Part I of this article, published in the March 2010 issue of the Kennedy Institute of Ethics Journal, traces and addresses the provision of unproven stem cell treatments in Russia and India, examines the concept of innovative treatment, and concludes that stronger regulations are needed to protect the health and informed choices of patients. The current paper, Part II, proposes that the regulatory frameworks for the development of safe and efficacious treatments in effect in the United States and the United Kingdom provide examples of strong oversight measures from which countries seeking to obtain international credibility for their biotechnological competence could draw when developing regulations for stem cell treatments. Major sources of information available to persons who consider receiving such unproven treatments are explored in order to understand and address their concerns. The paper concludes with proposed measures to inform those considering the pursuit of unproven stem cell treatments abroad more accurately about their efficacy and safety and provide them with improved medical and social support in their home countries.