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Biomedical subjects

N E Williams

Publications and source records attributed to N E Williams.

At least 37 records · Page 2Linked to original sources

Spread of local anaesthetic solutions following sacral extradural (caudal) block: influence of posture.

Extradural sacral (caudal) block was performed in 17 cases (14 patients) of chronic low back pain. In each case 22 ml of a bupivacaine/methylprednisolone solution incorporating a radioopaque dye was injected over a 2-min period. Patients were randomly assigned to receive the injection in the horizontal position or with 15 degrees head-up or head-down tilt applied to the operating table. Results indicate that analgesia is usually more localised than spread of solution determined by x-ray evidence and that higher levels of analgesia are achieved in patients in the head-up position. Possible causes are the differing distribution characteristics of the constituents of the solution and the gravitational effects of posture on cerebrospinal fluid mechanics. Technical problems associated with obesity, congenital abnormalities, vascular uptake of solution, and delayed spread of the injectant due to adhesions are discussed.

Anesthetics, Local↗

Differential effects of neuromuscular blocking agents on suxamethonium-induced fasciculations and myalgia.

The effect of pretreatment with suxamethonium, gallamine or pancuronium on suxamethonium-induced fasciculations and myalgia was studied in a controlled, randomized and double-blind clinical trial. Both fasciculations and myalgia were assessed on a four-point rating scale. There was no significant correlation between fasciculations and postoperative muscle pain at 24, 48 or 72 h, and pretreatment with suxamethonium had no significant effect on fasciculations or myalgia. Gallamine had a more marked effect on fasciculations than pancuronium, and the decrease in the fasciculation score was statistically significant. In contrast, pancuronium had a greater effect on myalgia, and decreased postoperative muscle pain significantly at 24 and 48 h. These differences may reflect the differential activity of gallamine and pancuronium at the neuromuscular junction. Pretreatment had little or no effect on plasma potassium concentrations.

Adolescent↗

The assembly and positioning of cytoskeletal elements in Tetrahymena.

The oral skeleton of Tetrahymena is a precisely arranged assemblage of basal bodies, microtubule bundles and connecting filaments found associated with the feeding structure in this cell type. Tubulin and filament proteins have been isolated but no actin has been recovered. The conditional mutant NP1 of Tetrahymena thermophila forms a normal oral skeleton at the permissive temperature (28 degrees C), but forms an abnormal one at the restrictive temperature (37 degrees C). Antibodies against tubulin and oral filament protein OF1 were used to visualize the abnormal oral skeleton and stages in its development, and ultrastructural comparisons of abnormal and wild-type oral skeletons were made. It was found that the overall pattern of organization was altered in the mutant, whereas the substructure appeared everywhere to be normal. Studies of cells in which the mutant phenotype was coming to expression revealed that normal basal bodies in the oral skeleton failed to move from the disordered state characteristic of early stages of development into the correct pattern of four organized clusters characteristic of later stages. Together, these results suggest that the lesion in NP1 does not affect cytoskeleton assembly per se, but instead affects a discrete mechanism responsible for the positioning of cytoskeletal elements with respect to each other after they have been formed (meta-assembly). Reasons for suspecting the involvement of the membrane skeleton are presented.

Animals↗

Regional differentiation of the membrane skeleton in Tetrahymena.

Antisera have been raised in rabbits against three high molecular weight proteins that are present in Triton X-100-insoluble residues of Tetrahymena pyriformis GL cells. These proteins, called A, B and C, have apparent molecular weights of 235, 135 and 125 (X 10(3)), respectively, in SDS-polyacrylamide gels. The antisera obtained are specific for these proteins, as shown by immunoblotting. Immunolocalization studies are reported that suggest that these proteins are present throughout the epiplasmic layer beneath the cell surface (membrane skeleton). Images obtained with the fluorescence microscope, however, suggest that the membrane skeleton is modified in discrete zones: (1) around somatic basal bodies, (2) within the oral apparatus, (3) in the cytoproct, (4) in contractile vacuole pores, (5) in the fission zone in late division, and (6) at the mating junction in conjugating cells. These regions may represent areas of increased rigidity at the cell surface. The transition from pliable to rigid epiplasm in spatially delimited areas is apparently a recurring theme in cortical morphogenesis in Tetrahymena. Together, the two types of epiplasm probably allow for extensive changes in cell shape while preserving essential relationships between structural elements within the cortex.

Animals↗

Oral filament proteins and their regulation in Tetrahymena pyriformis.

Two proteins from the Triton X-100-insoluble fraction of Tetrahymena pyriformis have been isolated and shown by immunological methods to be major components of a pervasive system of filaments localized within the oral apparatus. These proteins, OF-1 and OF-2, have apparent molecular weights (MWapp) in polyacrylamide gels of 87,000 and 80,000 D, respectively. Peptide maps obtained and the absence of immunological cross-reactivity suggest that these proteins are not closely related to each other. Indirect immunofluorescence studies on dividing cells have shown that the oral filament system forms late in the cell cycle. The filaments appeared first after the basal bodies in the oral primordium had organized into groups and the fission furrow had begun to form. Dedifferentiation of the oral filament system in the anterior (old) oral apparatus was also observed at this point in the cell cycle. Following this, the oral filament systems in both old and new oral apparatuses completed development synchronously. Proteins showing antigenic similarity to OF-1 were found in a number of other cell types. Tests with heterologous antisera failed to demonstrate a relationship between vertebrate cytoskeletal proteins and the oral filament proteins of Tetrahymena.

Animals↗

Buccal morphine--a new route for analgesia?

The analgesic effects of buccal and intramuscular morphine were compared in a prospective, double-blind, double-dummy study in forty patients who experienced pain after elective orthopaedic operations. Each patient simultaneously received a buccal tablet and an intramuscular injection, only one of which contained morphine sulphate (13.3 mg); the patients were randomly allocated to two equal groups so twenty patients received each active preparation. The two preparations produced a similar degree of postoperative analgesia, assessed by the mean reduction in pain score and the pain relief score. Peak plasma morphine concentrations were slightly lower after buccal than after intramuscular administration but they declined more slowly; consequently, the drug's bioavailability was 40-50% greater after buccal than after intramuscular administration. The adverse effects of buccal morphine were generally less than those of intramuscular morphine.

Administration, Oral↗

Postoperative analgesia with Duromorph.

The analgesic effects and bioavailability of a slow-release preparation of morphine (Duromorph) were studied in 12 patients with acute postoperative pain. Duromorph produced significant analgesia within 1-2 h of administration i.m., and there was a progressive decrease in the mean pain score for at least 8 h. None of the patients requested or received additional analgesia within 12 h, and the incidence of side-effects was similar to that associated with i.m. morphine. During the 8-h study, plasma concentrations of morphine slowly increased for 3 h, and then gradually declined. After 3 h, concentrations were invariably greater than those produced by conventional doses of morphine sulphate i.m. The study confirmed that Duromorph was an effective analgesic with a prolonged duration of action, which was suitable for the management of postoperative pain.

Adult↗

Expression of a cell surface immobilization antigen during serotype transformation in Tetrahymena thermophila.

A temperature shift from 40 to 28 degrees C rapidly induced expression of a specific immobilization antigen at the cell surface in Tetrahymena thermophila. This transformation was inhibited by actinomycin D and cycloheximide but not by colchicine or cytochalasin B. The major surface antigen expressed at 28 degrees C in cells homozygous for the SerH3 allele was partially purified, and an antiserum against this preparation was raised in rabbits. Electrophoresis, immunoblot, and [35S]methionine incorporation studies are reported which support the conclusion that the H3 antigen is an acidic protein with an Mr of approximately 52,000 daltons. An induced synthesis of the H3 immobilization antigen was detected within 30 min after a shift from 40 to 28 degrees C. This protein appeared to be synthesized in the microsomal fraction and transferred without cleavage to the cell surface, where it was inserted first into nonciliated regions.

Animals↗

Prolonged release extradural morphine.

The effects of extradural administration of a microcrystalline preparation of morphine (Duromorph) were studied in 5 patients with postoperative or malignant pain. As assessed by pain scores on a visual analogue scale, the effects of the analgesic were extremely variable; the best results were obtained in patients with postoperative pain. Two patients with chronic pain due to malignant disease developed slow respiratory rates. The plasma concentration of morphine usually followed a biphasic pattern; an initial peak between 0.5 and 1.5 hours was succeeded by a second, large peak between 6 and 12 hours. There was little or no apparent relation between the plasma concentration of morphine and the relief of pain, suggesting that Duromorph may have a local effect on the spinal cord.

Aged↗

Quantitative capillary column gas chromatographic method for the determination of glycopyrronium in human plasma.

A new sensitive and selective capillary column gas chromatographic method for the anti-cholinergic agent glycopyrronium bromide in human plasma is described. The procedure involves preliminary ion-pair extraction of the drug into dichloromethane, followed by concentration and analysis of the ion-pair complex by capillary column gas chromatography using a nitrogen-sensitive detector. The method depends on the thermal dequaternisation of the quaternary ammonium compound and can be used to detect 5 ng/ml in a 3-ml plasma sample. The assay procedure has been applied to the determination of the plasma concentration of glycopyrronium after intravenous administration to an anaesthetised patient.

Benzilates↗

Elimination of phenoperidine in liver disease.

The disposition and elimination of phenoperidine was studied in five normal subjects, and in six patients with hepatic disease. Plasma concentrations of phenoperidine were generally higher in patients with hepatic dysfunction. Secondary peaks were observed between 15 and 105 min (particularly in patients with liver disease). In the patients the terminal half-life of phenoperidine was prolonged by approximately 50%, mainly because of a decrease in the clearance of the drug. There was little or no change in the total apparent volume of distribution. However, the differences between normal subjects and patients with hepatic disease were not statistically significant. The results suggest that slight or moderate impairment of hepatic function does not significantly affect the kinetics of the drug, and that modification of its dosage may not be required.

Adult↗

Membrane protein differences correlated with the development of mating competence in Tetrahymena thermophila.

Initiation is the contact-independent phase of sexual conjugation which occurs when mature cells of Tetrahymena thermophila are shifted from growth medium to a low-salt starvation buffer. Immaturity, like high-salt starvation, restricts the ability of cells to conjugate; immature cells do not conjugate in either low- or high-salt buffers. Comparisons between sexually mature cells starved in initiation-restrictive and initiation-permissive buffers, and between immature and mature cells starved in an initiation-permissive buffer permitted the analysis of membrane protein expression correlated with mating competence. No polypeptides identified by lactoperoxidase-catalyzed iodination were found to be specific to mating-competent cells; however, several polypeptides not present in initiated cells were found to be common to the cell surfaces of immature and non-initiated cells which suggests that (1) initiation involves the removal of specific proteins from the cell surface, and (2) immaturity may be due to an inability to initiate.

Conjugation, Genetic↗

Shoulder-out immersion in pregnant women.

In the laboratory, water immersion or lower body positive pressure produces significant diuresis and natriuresis. Shoulder-out immersion appeared to induce significant diuresis and natriuresis in 42 pregnant women who were exercising in swimming pools. Lower body positive pressure (pressure calf sleeves) or Hubbard tanks (bathtubs) was not associated with increased renal function. In selected pregnant women with abnormal water distribution, shoulder-out immersion may prove to be effective therapy.

Blood Pressure↗

Plasma concentration of pyridostigmine during the antagonism of neuromuscular block.

The plasma concentrations of pyridostigmine were measured in eight patients during the antagonism of non-depolarizing neuromuscular blockade. After the injection i.v. of pyridostigmine bromide 14.6 mg/70 kg, the concentration of the drug rapidly decreased between 2 and 7 min, and then declined more slowly. After 2 h, significant amounts of pyridostigmine were still present in the plasma of all subjects. In the eight patients studied, the initial half-life was 1.0 +/- 0.3 min and the terminal half-life was 46.4 +/- 6.5 min (mean +/- SEM). Total body clearance of pyridostigmine was 8.7 +/- 1.5 ml min-1 kg-1, and the total apparent volume of distribution was 536 +/- 80 ml kg-1. Possible explanations for the differences between these results and previous studies are considered.

Adult↗

Effect of antacids on the plasma concentration of phenoperidine.

The effect of antacids on the plasma concentration of phenoperidine was studied in six volunteers. All subjects received the same dose of phenoperidine (15 micrograms kg-1) on different occasions in the presence, and absence of, an antacid preparation. In control studies, secondary peaks in the plasma concentration of phenoperidine were invariably observed; these were entirely eliminated, or modified substantially, by the concurrent administration of antacids. In the latter conditions, plasma concentrations of phenoperidine were greater during the first 20 min, and the area under the plasma concentration--time curve between 0 and 20 min was significantly greater than in control studies. In contrast, the plasma clearance of the drug was almost identical in control conditions and during treatment with antacids. After the oral administration of phenoperidine to two subjects, the systemic bioavailability of the drug was 9.9% and 13.9% respectively.

Administration, Oral↗

Intraoperative bradycardia and hypotension associated with timolol and pilocarpine eye drops.

A 69-yr-old man, who was concurrently being treated with pilocarpine nitrate and timolol maleate eye drops, developed a bradycardia and became hypotensive during halothane anaesthesia. Both timolol and pilocarpine were subsequently identified in a 24-h collection of urine. Timolol (but not pilocarpine) was detected in a sample of plasma removed during surgery; the plasma concentration of timolol (2.6 ng ml-1) was consistent with partial beta-adrenoceptor blockade. It is postulated that this action may have been enhanced during halothane anaesthesia with resultant bradycardia and hypotension. Pilocarpine may have had a contributory effect.

Aged↗