Haloperidol pharmacokinetics following gastric bypass surgery.
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Biomedical subjects
Publications and source records attributed to R B Stewart.
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Three rats were trained and given extensive experience with an operant-conditioning model of alcohol self-administration which produces pharmacologically significant drug intake. In this model, lever presses on a fixed ratio (FR) schedule of reinforcement allowed the animal brief access to an 8% (w/v) alcohol solution. Drug intake was then assessed when the animals were given a low-sodium diet and a low-sodium diet in combination with injections of the salt-losing diuretic furosemide (Lasix). In all cases, the low-sodium diet/furosemide treatment produced a substantial reduction in drug self-administration without changing water self-administration. In one case, introducing furosemide into the home-cage drinking water without a change of diet also brought about a decrease in alcohol self-administration. The low-sodium diet alone was ineffective in this regard. These findings corroborate earlier work using this form of treatment and are discussed in terms of the possible functional mode(s) of action of the treatment. The viability of this treatment for human drug-taking is also considered.
Ethanol-induced motor impairment in rats was measured following a number of different dietary or drug treatments. A low sodium diet combined with injections of the diuretic furosemide, but not a low sodium diet alone, increased motor impairment while a high sodium diet decreased impairment. Blood ethanol measurements indicated that both effects were probably mediated by changes in blood ethanol levels. However, the synthetic mineralocorticoid, DOCA, and the nonsteroidal anti-inflammatory, indomethacin, both altered ethanol-induced motor impairment without concomitant changes in blood ethanol levels. The aldosterone antagonist, spironolactone, failed to produce any effect. Since all treatments can modulate activity in the renin-angiotension system, this system appears to play a role in altering some of the behavioral properties of ethanol.
The hypothesis was examined that the interaction of ethanol with the conditions under which it is administered may determine whether either preference or aversion for the drug develops. In Experiment 1, eight groups of food-deprived rats received injections of ethanol (175-1,400 mg/kg) in one environment and were later offered a choice between that environment and a different one previously associated with saline injections. Another eight groups were treated identically, except that food was available in both the saline and ethanol-paired environments. The groups given the drug without food showed no preference or aversion at low doses (175-700 mg/kg), but showed aversion at higher doses (1,000 and 1,400 mg/kg). When food was available, there was an increased preference for the environment paired with the 500 mg/kg dose and reduced aversion at the 1,000 and 1,400 mg/kg doses. In Experiment 2, placing two rats together increased each rat's preference for the environment associated with the other animal. However, rats pretreated with 500 mg/kg ethanol before being placed together showed a reduced preference for the environment associated with the drug and the other animal. Controls never paired with another rat showed no preference or aversion at the same ethanol dose. Thus, ethanol may interact with conditions such as the presence of food or another animal to determine final effects that are unique to those conditions.
A total of 525 specimens from 100 slaughter beef cattle were examined for the presence of Campylobacter jejuni and Campylobacter coli by direct plating and enrichment techniques. Isolates were identified by cultural, biochemical, antibiotic sensitivity, and immunofluorescence tests and further characterized with the aid of recently developed biotyping and serotyping methods. Fifty animals were positive for C. jejuni; only one was positive for C. coli. The distribution pattern of C. jejuni-positive animals, in decreasing order, was steers (55%), bulls (40%), heifers (40%), and cows (22%). Significantly higher isolation rates were obtained from the gall bladders (33%), large intestines (35%), and small intestines (31%) than from the livers (12%) or the lymph nodes (1.4%). C. jejuni isolation by the enrichment technique was 40.2% more frequent than by direct plating; 24-h enrichment resulted in 24% more isolations than 48-h enrichment. Eighty-four of 105 C. jejuni cultures were typable serologically and represented 13 serogroups. Biotype I accounted for 71% of biotyped cultures. Serogroup 7 biotype I was the most commonly encountered (24%) isolate. About one in three positive animals had C. jejuni strains representing more than one serogroup. C. jejuni serogroups encountered in slaughter cattle were similar to those commonly isolated from human sources.
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Antianxiety agents' effects on the reported frequency of fainting, dizziness, loss of consciousness, and bone fractures were studied in a large ambulatory elderly population. The frequency of these symptoms in participants using seven different antianxiety drugs and that of a control group were compared. Dizziness and episodes of loss of consciousness and falls were reported more frequently in women using these drugs compared with controls (p less than 0.04 and p less than 0.01, respectively). There was an increase in reported bone fractures (12.1 percent to 9.4 percent) in women using antianxiety agents when compared with controls. All central nervous system symptoms were reported more frequently in participants using these drugs when compared with controls. This study suggests that chronic use of antianxiety agents in elderly patients may result in disabling central nervous system side effects.
The enrichment feature of a selective serum-based transport medium for Campylobacter fetus was quantitatively examined. Preputial samples from artificial insemination bulls were spiked with known numbers of C fetus strains and inoculated into transport-enrichment medium (TEM). The survival and multiplication of these strains in TEM under different incubation periods and temperatures were assessed by plate counts. Mean enrichment values of 3.72 log and 4.42 log were observed after incubation at 37 degrees C for two and four days, respectively. There was no significant difference in the enrichment values between the C fetus subspecies venerealis strains and a C fetus subspecies fetus strain. Incubation of inoculated TEM vials at room temperature for up to two days neither improved the growth of C fetus nor affected its subsequent enrichment when the vials were reincubated at 37 degrees C. Comparison of the survival of C fetus with and without the use of TEM under simulated transport conditions demonstrated the superiority of TEM.
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The extent of propranolol protein binding was determined in three different age groups of healthy drug-free caucasian males. Volunteers selected for study were 6-15 years old, 25-36 years old and 68-76 years old. Ten milliliters of blood were obtained via venipuncture and collected in glass tubes from the subjects after an overnight fast. Binding determinations were performed by equilibrium dialysis using radiolabelled propranolol. Serum albumin and alpha 1-acid glycoprotein concentrations were determined in all subjects by radial immunodiffusion. The results obtained showed wide intersubject variability in the binding ratio of propranolol and serum concentrations of alpha 1-acid glycoprotein. Mean albumin serum concentration was found to be significantly lower in the elderly group as compared to the adult and pediatric groups (p less than 0.02). A positive correlation was found between the binding ratio of propranolol and the serum concentration of alpha 1-acid glycoprotein in all the subjects (r = + 0.66, p less than 0.005). No significant correlation was found between the binding ratio of propranolol and the serum concentration of albumin (r = -0.03, p less than 0.88). These data suggest that the extent of propranolol binding is influenced primarily by serum concentrations of alpha 1-acid glycoprotein and not by differences in age.
Procedures almost exclusively involving the use of operant conditioning equipment have been successful in training rats to drink ethanol and establishing ethanol as a reinforcer. The present report describes a variation of this procedure which, in a relatively short period of time also establishes ethanol as a reinforcer, results in significant blood ethanol levels, but does not require extensive programming or recording equipment and is therefore more amenable to studies in which large numbers of animals are required.
The effect of a salt supplemented diet on the voluntary intake of ethanol in male Wistar rats was examined in two experiments. In Experiment 1, the addition of 3% sodium chloride to the diet selectively increased the intake of moderately concentrated ethanol solutions (3 and 6%) while leaving the choice of a 12% solution unaffected. The choice and intake of water in the two former groups declined. In a second experiment four different groups of rats were offered the 3% salt supplemented diet in combination with daily injections of the synthetic salt-retaining mineralocorticoid desoxycorticosterone acetate (0.5, 1.5, and 6.0 mg/day). Ethanol intake again tended to increase in the 3 and 6% groups but in contrast to the results of Experiment 1 water intake also increased significantly. When desoxycorticosterone was administered without the salt supplemented diet, ethanol intake was significantly depressed while water intake increased. These findings indicate that a salt supplemented diet can significantly and selectively enhance the intake of moderately concentrated ethanol solutions and that while the addition of desoxycorticosterone injections to this diet has its effect primarily on water intake, these injections alone can also suppress ethanol intake indirectly by shifting the animals choice toward water and away from ethanol.
The effects of antihypertensive agents on the frequencies of reported fainting, dizziness, losses of consciousness, and bone fractures were studied in a large, ambulatory elderly population. The frequencies of these symptoms were compared for subjects who used one or more of nine different antihypertensive agents and for subjects who were not using these medications and who served as a control group. Over 40 per cent of the total population were using at least one of the nine drug groups. Women who used antihypertensive medications reported significantly more fainting (P less than 0.001), dizziness (P less than 0.005) and "blacking-out spells" (P less than 0.002) but significantly fewer bone fractures (P less than 0.02) compared with women who were not using such medication in the control group. For men, the use of only one drug group, propranolol, was associated with a significant increase in fainting and dizziness but not blacking-out spells compared with men in the control. These results suggest that elderly persons may be subject to a variety of central nervous system side effects induced by antihypertensive drugs.
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The ability of ethanol to motivate avoidance responding was used as a measure of the drug's aversive stimulus properties. In Experiment I, four groups of rats were infused with either ethanol (200, 400, 800 mg/kg IV) or saline if they failed to jump a high hurdle. The ethanol groups acquired the jumping response (active avoidance), while the saline group only showed a tendency not to jump. In Experiment II, the hypothesis was tested that the same infusions might be self-administered if the contingency were reversed so that responses produced rather than avoided the drug. Four groups of rats were given the same doses of ethanol or saline if they traversed a runway and entered a goal box. Initially, all animals made the response, however the drug-treated groups eventually showed a dose-dependent tendency to refrain from entering the goal box (passive avoidance). Thus ethanol can maintain behavioral control similar to that produced by commonly used aversive stimuli (e.g. foot shock) and can do so at lower doses than those found to be effective in previous reports of ethanol-mediated aversions. It is suggested that the mechanism by which ethanol comes to be a reinforcing agent must take into account the pervasive negative properties of the drug.
Antacid use was studied in a population of 3192 elderly ambulatory subjects. Antacids were used by 18.6% of women and 12.9% of men. Three common antacid products accounted for 63.8% of all antacids used by these subjects. Serum phosphorus concentrations of participants using aluminum antacids were significantly lower than in a nonantacid user control group (P less than 0.02). Total protein and serum calcium concentrations of subjects using aluminum and magnesium combination antacid products were significantly lower than the control group (P less than 0.001 and P less than 0.04). Men using calcium carbonate antacids reported diarrhea significantly more frequently than control subjects.