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Biomedical subjects

T Baker

Publications and source records attributed to T Baker.

At least 73 records · Page 4Linked to original sources

Smoking prevention: towards a process approach.

Current studies of smoking prevention treat the adolescent as a target of influence, they emphasize the acquisition of skills for resisting peer pressure and give too little attention to motivation for resistance. Studies consistent with this social learning framework show moderate reductions in the incidence of smoking for the short term; recent, long-term follow-ups show no reduction in experimental over control conditions. We propose a re-examination of the influence framework and suggest that adolescents use smoking and dress, to project an image of self that will increase the likelihood of success in the formation of relationships in which participants share feelings and attitudes toward each other and the adult world. We also suggest that adults focus upon external, perceptible, and remote threats, e.g. smoking is seen as evil, a response to peer pressure, and a long term threat to health, and ignore discourse about proximal, subjective feelings respecting the changing sexual urges and feelings of social anxiety that accompany adolescence. The socialization of these affects is left to the peer group. It is suggested that future programs intensify their focus on motivation for resisting smoking based upon a revised view of the adolescents objectives in self definition, and combine this with the best of the current skills approaches.

Adolescent↗

Effects of oral phosphocysteamine and rectal cysteamine in cystinosis.

Diurnal variation in leucocyte cystine and the effects of equimolar single doses of oral phosphocysteamine and rectal cysteamine were studied in eight patients with cystinosis, aged 1.8-16.5 years. No significant diurnal variation in leucocyte cystine was found. Absorption of cysteamine was reduced after rectal administration compared with the oral dose: mean (SD) peak concentration 17.2 (6.3) mumol/l v 36.4 (5.5) mumol/l at 40 min and mean (SD) area under the curve 22.3 (14.3) v 59.4 (33.1) mumol/h/l. Oral phosphocysteamine significantly reduced the mean (SD) leucocyte cystine from 8.09 (0.47) to 3.26 (1.48) nmol 1/2 cystine/mg protein at three hours. At 12 hours the mean leucocyte cystine was significantly lower than the pretreatment concentration. Rectal cysteamine did not significantly reduce the mean leucocyte cystine concentration. In conclusion, phosphocysteamine suspension may be administered every 12 hours. Rectal cysteamine administration is feasible but higher doses are required before efficacy can be judged.

Administration, Oral↗

Postpartum cardiovascular complications after bromocriptine and cocaine use.

A case is presented of a postpartum woman in whom hypertension and pulmonary edema developed after administration of bromocriptine mesylate. Caution is advised when there is additional recent use of cocaine because of a suggested potentiating action of cocaine on the development of adverse cardiovascular and cerebral sequelae in postpartum patients who take bromocriptine.

Adult↗

Activity-dependent differences between rat fast and slow neuromuscular systems.

Activity-dependent pharmacologic differences between the fast tibialis anterior and slow soleus neuromuscular systems of the rat were studied. The tibialis anterior was more sensitive than the soleus to d-tubocurarine tetanic fade (50 Hz), as determined from recordings of compound muscle action potentials. Pre-treatment with physostigmine prevented curare-induced tetanic fade in the tibialis anterior, but not the soleus. Additionally, when contractile tension was 80% blocked by d-tubocurarine, the tibialis anterior was more responsive than the soleus to the decurarizing action of tetanic stimulation (25, 50 and 100 Hz). These results disclose that activity-dependent pharmacologic differences exist between neuromuscular systems. Further, they indicate that the tibialis anterior and the soleus differ in their processes of transmitter release. It is speculated that differences in nerve terminal Ca2+ account for the observed pharmacologic differences between the tibialis anterior and soleus.

Action Potentials↗

Comparison of technetium-99m MAG3 with iodine-131 hippuran by a simultaneous dual channel technique.

Technetium-99m MAG3, a technetium-labeled analog of hippuran, was compared with [131I] hippuran using a simultaneous dual isotope study in 20 patients. The plasma clearance for MAG3 was lower than that of hippuran, but its plasma concentration was higher, resulting in similar rates of excretion and similar renal time-activity curves. Apart from better statistics with the technetium-labeled agent, there were no clinically significant differences in this group of patients.

Adult↗

Response of delta (0-3 Hz) EEG and eye movement density to a night with 100 minutes of sleep.

In one of a series of experiments aimed at gathering the empirical data required to formulate mathematically our recovery model of sleep, we recently (1) measured the increase in delta electroencephalogram (EEG) following one night of total sleep deprivation (TSD). We found that the delta rebound was confined to the first non-rapid eye movement period (NREM-P1) of recovery sleep; this unexpected result was documented with direct computer measurement of 0-3 Hz EEG, as well as with visual scoring of stages 3 and 4. We also found a robust decrease in eye movement density during the second and third REM periods, which we hypothesized to be due to the increased depth of recovery sleep. In the present experiment, we awakened young adult subjects after 100 min of sleep, a duration that includes the first cycle for this age group, and analyzed visual and computer measures of delta and eye movement density during recovery sleep. We again found eye movement density to be significantly reduced in REM-P2 and P3, but to a lesser degree than after total sleep deprivation, a condition that may be presumed to produce a greater increase in sleep depth. Delta increases were again limited to the first cycle, although all subjects completed this cycle on the 100-min night. The major difference between recovery sleep patterns following the total deprivation and the 100-min sleep conditions was that 0-3-Hz wave amplitude increased significantly after the former, but not after the latter. In both studies, recovery sleep showed increased 0-3-Hz wave density. The neurophysiological implications of a response of EEG amplitude as opposed to wave density are briefly considered; separate measurement of these variables is more readily accomplished with period-amplitude than with spectral analysis. Our results further illustrate the importance of measuring sleep by physiological units, such as the successive NREMPs and REMPs. They also support other data that indicate that NREM-P1 plays a special role in human sleep: it responds selectively to sleep deprivation, shows the greatest ontogenetic variation across the human lifespan, and is the component of sleep that is most frequently abnormal in psychiatric patients. As we have long argued, it is inappropriate to conceptualize this high priority component of NREM sleep as "REM latency" and as a measure of REM "pressure" exclusively.

Adult↗

Drug delivery using vesicles targeted to the hepatic asialoglycoprotein receptor.

We assessed the utility of liver-targeted vesicles as a drug delivery system for the treatment of liver diseases. Small, unilamellar vesicles (mean diameter, 60-80 nm) composed of dipalmitoylphosphatidylcholine, cholesterol, dipalmitoylphosphatidylglycerol and digalactosyldiacylglycerol (mol ratios, 40:40:5:15) are rapidly cleared from the blood in rats after intravenous injection. In vivo organ distribution shows that the liver is the major site of vesicle accumulation, with roughly 60-80% of the vesicle contents delivered to the liver. Isolated, perfused rat liver experiments show that the uptake is due to the hepatic asialoglycoprotein receptor, and the uptake process occurs with minimal vesicle leakage. At low doses of the vesicles, the single pass extraction by the liver is around 50%, which means that this vesicle formulation operates close to optimal efficiency as a drug delivery system to the liver. Binding of vesicles to the liver was determined to saturate at 6.5 mg total lipid/kg body weight, with a maximum steady-state turnover rate of vesicles at 37 degrees C of 79 micrograms lipid/min per kg body weight. This gives a receptor recycling time of around 80 min. We have incorporated this information into a pharmacokinetic model of vesicle distribution which quantitatively predicts the kinetics and dose dependence of vesicle uptake by the liver in vivo. This information can be used to optimize vesicle-mediated drug delivery to the liver.

Animals↗

Drug actions at mammalian motor nerve endings: the suppression of neostigmine-induced fasciculations by vecuronium and isoflurane.

The occurrence of fasciculations following administration of agents is a well-known pharmacologic phenomenon. Using the cat soleus nerve-muscle preparation, intravenous neostigmine doses between 20-200 micrograms/kg evoked fasciculations in a dose-related manner. The data demonstrate that the fasciculations were the result of the direct effect of neostigmine acting at the motor nerve endings. Vecuronium in a dose-related manner (3 and 5 micrograms/kg iv) suppressed this prejunctional activity of neostigmine. The prejunctional effect of vecuronium explains its effectiveness in preventing succinylcholine-induced fasciculations. In the presence of isoflurane (end-tidal concentration 0.20-0.25%), the suppressant effect of vecuronium on motor nerve endings was enhanced. The prejunctional action of isoflurane may be a major contribution to the additive effects of non-depolarizing muscle relaxants and potent inhalation agents.

Animals↗

A note on shelf-life extension of British fresh sausage by vacuum packing.

Vacuum packing of British fresh sausage in a low oxygen permeability film (Diolon) extended the product shelf-life at 6 degrees C to more than 20 d compared with 9-14 d in conventional packs. After 10 d storage, counts of key spoilage organisms such as yeasts and Brochothrix thermosphacta were generally 2 log cycles lower in vacuum packs. Vacuum-packed sausages also displayed a slower rate of loss of free sulphite. Variations in pack permeability to SO2 were not responsible for this. Losses of free SO2 in stored sausages are largely due to the production of sulphite-binding agents by yeasts. Selective enumeration of these yeasts showed them to be inhibited by conditions of vacuum packing. The extension of shelf-life observed is ascribed to the reduction in growth rate of the spoilage flora in vacuum packs coupled with the consequent maintenance of inhibitory levels of sulphite for a longer period.

Animals↗

Selection and optimisation of monoclonal antibodies for a two-site immunoradiometric assay for ACTH.

Four monoclonal antibodies with predominant specificities towards different sequences within the ACTH molecule were investigated in a 2-site immunoradiometric assay (IRMA) for human ACTH. Antibody 3H9 recognises the extreme N-terminal sequence, antibodies 1A12 and 1D1 are specific for the mid N-terminal sequence but differ in that the former cross-reacts with alpha MSH whereas the latter does not, and antibody 2A3 recognises the C-terminal sequence. Combinations of iodinated antibodies with antibodies covalently linked to Sephacryl S300 were tested for their compatibility and potential for a sensitive assay. Two antibody combinations (1D1 plus 3H9 or 1A12) gave no dose-response curve indicating severe steric inhibition, whereas other combinations yielded assays with widely different detection limits (2-2400 ng ACTH/l). The combination of labelled 1D1 and solid-phase 2A3 gave the most sensitive assay and when optimised for antibody concentrations and incubation times the working range was 10-5 X 10(4) ng/l (CV less than 20%). The optimised sequential 2-step IRMA involves incubation of standard or test sample with labelled 1D1 for 18 h at 4 degrees C followed by incubation with solid-phase 2A3 for 2 h at room temperature, after which the labelled complex is separated by the sucrose layering technique. The detection limit of this IRMA was several 100-fold lower than by RIA using the same antibodies. The IRMA detected large molecular weight precursors containing the full ACTH sequence (22 000, 31 000 and 34 000) but not ACTH fragments (1-18, 1-24, 18-39). It is concluded that selected monoclonal antibodies provide a sensitive and rapid 2-site IRMA for intact ACTH and its precursors.

Adrenocorticotropic Hormone↗

The potential for optimal (less than or equal to 2 cm) cytoreductive surgery in advanced ovarian carcinoma at a tertiary medical center: a prospective study.

From November 1980 to April 1985, 50 consecutive previously untreated patients with FIGO Stage III and IV ovarian cancer were entered into a prospective trial to evaluate what percentage of such patients could have their tumors optimally cytoreduced (residual cancer less than or equal to 2 cm), what operation is required to achieve this goal, and what is the associated morbidity. Optimal cytoreduction was achieved in 76% of the 50 cases and in 77% of 18 cases referred as "inoperable." To achieve this goal, the six most common operations performed in descending order of frequency were bilateral salpingo-oophorectomy (100%), hysterectomy (98%), omental resection (86%), peritoneal tumor resection (40%), intestinal resection (36%), and gastrocolic ligament resection (16%). Fifty-eight percent of the patients had no major complications. The most significant complications were congestive heart failure in 4% and pulmonary embolus in 4%. Ninety-four percent of the patients had chemotherapy initiated in less than or equal to 14 postoperative days. It is concluded that approximately three-fourths of patients with advanced Stage III and IV ovarian carcinoma can have their tumors resected to less than or equal to 2 cm in greatest diameter. The value of such therapy on ultimate response to chemotherapy and survival will have to await longer follow-up, and will be the subject of a subsequent report.

Adenocarcinoma↗

Prejunctional effects of vecuronium in the cat.

This study explored the prejunctional actions of vecuronium using the in vivo cat soleus nerve-muscle preparation. Vecuronium doses of 1 to 5 micrograms/kg iv suppressed the repetitive firing of the motor nerve endings, and the obligatory potentiation of the twitch response following high-frequency conditioning at 400 Hz for 10 s without attenuating neuromuscular transmission at 0.4 Hz. It was also found that extremely low doses of vecuronium had excitatory effects at the cat soleus motor nerve endings: doses of 0.5 and 1 microgram/kg iv evoked a modest postdrug repetitive firing of the nerve endings and a concomitant potentiation of the muscle responses. These dose-related agonist and antagonist activities suggest that at the motor nerve endings, vecuronium is a weak partial agonist. The major action of vecuronium at the motor nerve endings, however, was suppressive, and this antagonist action contributed to the neuromuscular blocking action of this muscle relaxant.

Action Potentials↗

d-Tubocurarine sensitivities of a fast and a slow neuromuscular system of the rat.

Fast and slow neuromuscular systems in the rat were compared with respect to their sensitivity to d-tubocurarine (dTC). The fast tibialis anterior was more sensitive than the slow soleus to dTC-induced block of contractile tension when stimulated at either 0.2 or 1.0 Hz. These results in the rat contrast those made by others in the cat. Thus, relative drug sensitivities are not simply related to neuromuscular type.

Animals↗

Prolongation of procaine's and procainamide's actions by binding to acryloyl polymers.

Procaine and procainamide were covalently bound to acryloyl monomers and polymers. The dose-response and time-action parameters of the cardiac antiarrhythmic protection afforded by the prototype drugs and their acryloyl derivatives against chloroform-hypoxia-induced cardiac arrhythmias in unanesthetized mice and epinephrine-induced arrhythmias in alpha-chloralose anesthetized cats were determined. Similarly, the pharmacological parameters which characterized their acute toxic responses in unanesthetized male albino mice were also determined. The similar pharmacological spectra of their activity and the parallelism of their lethal dose-response curves indicate that the active constituents of the polymer derivatives are the local anesthetic moieties. Compared to the prototype drugs, the polymer derivatives were more potent on a molar basis and their pharmacological effects were prolonged. The increased potency and duration of action reinforce the idea that the local anesthetic moieties are pharmacologically active while still bound to the polymer backbones.

Acrylic Resins↗