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Biomedical subjects

M M Ghoneim

Publications and source records attributed to M M Ghoneim.

At least 109 records · Page 6Linked to original sources

A sensitive gas chromatograph assay for thiopentone in plasma.

A sensitive flame ionization gas chromatograph assay method has been developed for thiopentone in human plasma. The extraction procedure minimizes desulphuration of the drug while removing most endogenous substances and is limited by a maximum of 50 ng ml-1 in 2-ml plasma samples. There is linearity throughout the 30.0-5.0 microgram ml-1 and 5.0-0.1 microgram ml-1 ranges. Extraction of six replicate 2.5-microgram ml-1 samples resulted in a coefficient of variation of 3.0%. Similar treatment of six 0.20-microgram ml-1 samples afforded a coefficient of variation of 4.6%.

Flame Ionization↗

Pharmacokinetics of etomidate, a new intravenous anesthetic.

Etomidate sulfate, 0.3 mg/kg, was administered intravenously to eight patients and venous blood samples were drawn at intervals for the subsequent 10 hours. Plasma etomidate was determined by mass fragmentography. Plasma concentrations were fitted to a triexponential equation consistent with a three-compartment open pharmacokinetic model. Mean (+/-SD) variables were: initial t1/2, 2.6 +/- 1.3 min; intermediate t1/2, 28.7 +/- 14.0 min; apparent elimination t1/2, 4.6 +/- 2.6 hours; volume of the central compartment, 23.2 +/- 11.41; total apparent volume of distribution, 4.5 +/- 2.21/kg; fraction of drug in the central compartment, 7 per cent; total plasma clearance, 860 +/- 230 ml/min. Total blood clearance was estimated to be 754 ml/min and hepatic clearance, 739 ml/min. The large apparent volume of distribution indicates considerable tissue uptake. The hepatic clearance, being about 50 per cent of hepatic blood flow, indicates that changes in hepatic blood flow or hepatic metabolism will have only moderate effects on etomidate disposition.

Adolescent↗

Studies on human memory: the interactions of diazepam, scopolamine, and physostigmine.

Seventy volunteers were injected with diazepam (0.3 mg/kg), scopolamine (8 mug/kg), or placebo, followed 70 min later by another injection of physostigmine, physostigmine and methscopolamine (in case of diazepam treatment), or placebo. Physostigmine was given in two doses, 16 and 32 mug/kg; methscopolamine, 8 and 16 mug/kg. Subjects (Ss) were tested in groups of 5 in a double blind procedure with treatments distributed according to a Latin square design. Prior to treatment, Ss heard a series of lists of words, followed by an immediate recall test. Following the first injection, delayed free recall and recognition tests were given. The second drug was then injected, followed by a presentation of another two sets of lists which were tested similarly. Subjective feelings were also evaluated with a rating questionnaire. Diazepam and scopolamine did not affect recall of information which had been learned prior to drug injection. However, both drugs impaired the learning or acquisition of new information. Physostigmine, especially in its high dose, antagonized most of the memory deficits produced by scopolamine while those of diazepam remained. This is a strong indication that scopolamine acts centrally through an anticholinergic mechanism while diazepam may act through a different system.

Adult↗

Mass fragmentographic determination of plasma etomidate concentrations.

The intravenous anesthetic etomidate was measured in human plasma by mass fragmentography. The method is accurate, sensitive, and specific. Results of the analyses indicate that after a single 0.3-mg/kg iv dose of etomidate, there are at least three phases in its disappearance from human plasma. Detectable plasma concentrations exist for more than 6 hr after injection.

Etomidate↗

Binding of thiopental to plasma proteins: effects on distribution in the brain and heart.

Thiopental-14C (30 mg and 10 muCi/kg) was injected intravenously into rats 36-48 hours following bilateral nephrectomy and one minute after pretreatment with sulfadimethoxine (30 mg/kg, iv). Control groups of normal and sham-operated animals were used. The distributions of radioactivity in plasma, brain, and heart 1, 5, and 30 minutes after injection were examined. Uremic and sulfonamide-pretreated rats showed significantly higher levels of 14C in brain and heart and more free thiopental in plasma at each time than did control animals. There was a significant correlation between the free thiopental in plasma and total drug concentrations in the brain and heart. Uremic rats bound less thiopental in plasma compared with controls in spite of normal total plasma protein and albumin concentrations. It is concluded that reduced protein binding of thiopental leads to accelerated distribution and increased drug concentrations in the brain and and heart.

Animals↗

Effects of diazepam and scopolamine on storage, retrieval and organizational processes in memory.

The effects of intramuscular injections of diazepam (0.3 mg/kg) and scopolamine (8 mug/kg) on memory processes and subjective moods were studied in 36 volunteers. Subjects (Ss) were tested in groups of four in a double blind procedure with treatments distributed according to a Latin square design. Lists of words were presented to Ss who were then tested with an immediate free recall test prior to drug administration. Following injection delayed free recall and recognition tests were given. Subsequently two sets of lists were presented separately and tested in the same fashion. Two of the lists in the last set were composed of words falling into distinct categories. Memory was additionally analyzed by testing immediate recall of digit sequences and employing a visual recognition test. Subjective moods were evaluated with a rating questionnaire. Both diazepam and scopolamine impaired memory functions although the action of the latter drug was more pronounced and prolonged. The deficit appeared to be in the storage process leaving retrieval processes unaffected. Scopolamine in addition interfered with organizational processes. Subjectively, scopolamine also produced a larger sedative effect than diazepam.

Adult↗

The effect of diazepam and fentanyl on mental, psychomotor and electroencephalographic functions and their rate of recovery.

Ten healthy male subjects received diazepam (10 or 20 mg), fentanyl (0.1 or 0.2 mg) or a placebo intravenously at weekly intervals according to a latin square design. They were tested on a battery of psychological and electroencephalographic tests at 0.5, 2, 6, and 8 hrs following injection. Fentanyl had little effect on memory while diazepam reduced the ability to learn without increasing forgetting of material alread acquired. By the 2nd hour post injection, only the low dose of fentanyl had no residual effect. Recovery was complete by the 6th hour for all treatments according to the psychological tests except for the lagging effect of high dose of diazepam on memory. The electroencephalographic effects of diazepam persisted beyond the end of the testing sessions while those of the high dose of fentanyl recovered by the 8th hour. Thus in the dosages tested, diazepam had more intense and prolonged effects than fentanyl.

Adult↗

Binding of tubocurarine to specific serum protein fractions.

The binding of tritium-labelled tubocurarine to separate protein fractions of sera from normal subjects and patients with hepatic disease was measured by an electrophoretic technique. The binding of the drug to gamma globulin and albumin solutions also was studied using equilibrium dialysis. The major portion of the drug, 82-90%, was bound to the gamma globulin electrophoretic fraction of both normal and patient sera. However, as measured by equilibrium dialysis, only 15.8% of the drug was bound to the gamma globulin and 23.8% to albumin. Equilibrium dialysis yields the data by which the validity of other methods for measuring drug-protein binding can be judged. Since in a previous study we also found no difference in binding of the drug between healthy individuals and patients with hepatic disease, equilibrium dialysis measurements may reflect better the binding of the drug in vivo.

Alpha-Globulins↗

Plasma protein binding of thiopental in patients with impaired renal or hepatic function.

Binding of thiopental to proteins in plasma from healthy, cirrhotic, and uremic subjects was studied using equilibrium dialysis. In plasma from healthy volunteers 28.0 plus or minus 0.9 per cent of thiopental was unbound. In plasma from patients with hepatic disease 53.0 plus or minus 2.1 per cent was unbound, while in patients with renal disease 55.7 plus or minus 1.5 per cent remained unbound. The decreased binding in uremia could not be explained completely by competitive displacement by nitrogenous end products or by hypoalbuminemia, although hypoalbuminemia may account for the decreased binding in cirrhotic patients.

Binding, Competitive↗

Alteration of warfarin kinetics in man associated with exposure to an operating-room environment.

The plasma half-life of warfarin (mean +/- SE) in five normal, nonmedicated control subjects given a single 40 mg/m2 oral dose of warfarin was 38.8 +/- 4.1 hours. It was essentially the same (37.7 +/- 2.6 hours) in these subjects when determined again four months later. The effect of the single dose of warfarin on prothrombin complex activity (prothrombin response) was determined by calculating the area under the curve obtained by plotting prothrombin time (seconds) versus time after the warfarin dose (hours). The prothrombin response in control subjects was 1670 +/- 64 sec-hr initially and essentially the same at the end of the four-month interval (1730 +/- 96 sec-hr). Plasma warfarin half-life and prothrombin response in seven anesthesiology residents were 32.1 +/- 3.6 hours and 1337 +/- 78 sec-hr at the start of their training period, i.e., before working in the operating room. Four months later, their plasma warfarin half-lives were significantly prolonged (49.3 +/- 4.8 hours) and the prothrombin responses were significantly greater (1552 +/- 22 sec-hr) compared with their initial values. The alteration of warfarin kinetics appeared to be due mainly to inhibition of warfarin metabolism, presumably related to the repeated exposure of these subjects to an operating room environment.

Administration, Oral↗