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Biomedical subjects

P Anderson

Publications and source records attributed to P Anderson.

At least 379 records · Page 21Linked to original sources
PubMed1987

Priming and induction of Haemophilus influenzae type b capsular antibodies in early infancy by Dpo20, an oligosaccharide-protein conjugate vaccine.

A conjugate vaccine (Dpo20) was made by direct coupling of diphtheria toxoid and oligosaccharides obtained by periodate oxidation of Haemophilus influenzae type b capsular polysaccharide. This approach gave a higher multiplicity of saccharides per protein and greater immunogenicity in infancy than our previously studied conjugates. Thirty-three healthy infants received three sequential injections, and no serious side effects were observed. When Dpo20 was given with diphtheria-tetanus-pertussis vaccine at ages 2, 4, and 6 months, the geometric mean titer of anticapsular antibody rose to 5.9 micrograms/ml at age 7 months. Dpo20 given at 3, 5, and 7 months raised the mean to 3.2 micrograms/ml at 7 months (after two injections) and 15.4 micrograms/ml at 10 months. The antibodies included IgG and were bactericidal in vitro. Thus, antibody activities potentially protective against invasive H. influenzae b infections were induced in the most susceptible age range. The infants also became primed for mature-for-age responses to (unconjugated) polysaccharide vaccine given as a booster at age 12 months.

Age Factors↗
PubMed1987

Immunochemical variables affecting radioantigen-binding assays of antibody to Haemophilus influenzae type b capsular polysaccharide in childrens' sera.

In radioantigen-binding assays for antibody to Haemophilus influenzae type b capsular polysaccharide, an apparent antibody concentration [( (["Ab"]) is assigned to test sera on the basis of binding equivalence to dilutions of standard adult antiserum. In childrens' sera, ["Ab"] can disagree between laboratories and between intralaboratory assays using different preparations of radioantigen. Immunochemical variables causing disagreement include the dilution of test serum at which ["Ab"] is assigned and the concentration and size distribution of radioantigen. Binding-dilution curves of many childrens' sera displayed shallower slopes than did the standard, thus ["Ab"] increased with dilution, particularly in low-binding sera. An increase in radioantigen concentration also raised ["Ab"]. Using larger-sized radioantigen raised the binding in standard and childrens' sera comparably and thus would not directly affect ["Ab"] but would raise ["Ab"] indirectly by increasing the serum dilution. These results are theoretically predicted if the affinity of childrens' antibodies are lower than that of the standard.

Antibodies, Bacterial↗
PubMed1987

An evaluation of anti-insulin radioimmunodetection in patients with suspected insulinoma.

Nine patients with suspected insulinoma were scanned with iodine-131 labelled anti-insulin. The clinical diagnosis was subsequently confirmed at laparotomy in eight patients, two of whom had liver metastases. The primary insulinoma was accurately localized by anti-insulin scanning in four patients and these tumours ranged from 1 to 3 cm in diameter. Both computerized axial tomography (CT) scanning and pancreatic angiography had given false negative results in one of these patients. Hepatic metastases were correctly identified in one of two patients. No hepatic false positive reports occurred. Positive scan areas were graded as definite, probable or possible. All four of the pancreatic positive results graded as definite or probable positive were correct. Three false positive results occurred in the region of the pancreatic body, all had been graded as possible. Anti-insulin scanning failed to detect four subsequently proven insulinomata (3 mm-2 cm in diameter). Pelvic uptake of anti-insulin occurred in a patient who was found to have a para-ovarian tumour. An homogenate of this tumour also reacted with anti-insulin in a radioimmunoassay. A true negative pancreatic scan was obtained in this patient. We conclude that this technique is insufficiently accurate for routine clinical use.

Adenoma, Islet Cell↗
PubMed1987

Thresholds of action potentials evoked by synapses on the dendrites of pyramidal cells in the rat hippocampus in vitro.

1. In this study we have measured the thresholds of action potentials and some properties of e.p.s.p.s (excitatory post-synaptic potentials) produced by activation of distal and proximal dendritic synapses in CA1 pyramidal cells in rat hippocampal slices. 2. Simultaneous intracellular and extracellular electrophysiological recordings were made from pyramidal cells. The two recording electrodes were positioned very close together to provide an accurate measurement of the transmembrane potential by subtraction of the extracellular field from the intracellular potential. 3. Two pairs of stimulating electrodes were placed in the stratum radiatum of area CA1. The proximal and distal afferents were stimulated alternately within a 15 s cycle and at an intensity to produce action potentials in about 50% of the trials. 4. At this stimulus intensity there was a slight difference in the mean 10-90% rise times of the e.p.s.p.s produced by stimulation of proximal and distal afferents. The ratio of the distal: proximal rise time was 1.27. 5. In those trials where the action potential failed there was also a significant difference in the time-to-peak of the e.p.s.p.s evoked from proximal or distal sites. The times-to-peak of the e.p.s.p.s from proximal stimulation were between 1.5 and 3.8 ms, whilst the times-to-peak from distal stimulation were longer (2.1-7.2 ms). 6. In 16/18 cells included in this study the thresholds for action potentials evoked by distal stimulation were significantly lower than those following proximal activation. The mean threshold for distal activation was 12 mV compared with 16 mV for proximal activation. 7. The threshold of action potentials activated by depolarizing current pulses appeared to be close to that for action potentials evoked from proximal synapses. 8. Whilst the shape indices of the e.p.s.p.s were slightly different when comparing transmembrane with conventional intracellular recordings, the thresholds of the action potentials were not affected by this procedure. 9. Possible explanations for the low threshold for action potentials evoked from distal synapses are discussed, including an active dendritic membrane and differences in inhibition.

Action Potentials↗
PubMed1987

Limitations to the killing of tumours using radiolabelled antibodies.

We have calculated the minimum requirements for effective therapy using intravenously administered, tumour-directed antibodies labelled with either iodine 131 or yttrium 90. A lethally large amount of either radionuclide would be required to achieve tumour destruction. At least a 10-fold increase in tumour uptake is necessary to combine tumour destruction with a survivable whole-body dose. The required improvement in specific uptake can be substantially reduced by accelerating the excretion of radioactivity outside the tumour. For all situations studied, yttrium 90 is superior to iodine 131 as a cytotoxic label.

Antibodies, Monoclonal↗
PubMed1987

A method for thresholding subtracted images in radiolabelled-antibody imaging.

The low target-to-background ratio of radiolabelled antibodies often necessitates the use of a subtraction technique to enhance areas of tumour uptake. However, interpretation of the results is often difficult due to noise in the antibody and subtraction images. By performing a linear, least-squares fit to all the pixel values, it is possible to calculate the "prediction interval". This may be used as a variable threshold for the subtracted image to leave only statistically significant counts. The method has been evaluated in models and found to be independent of count density and image processing. Useful results have been obtained in initial patient studies. The technique is fast and objective, and therefore it may have a useful role in the routine analysis of subtracted images.

Antibodies, Monoclonal↗
PubMed1987

Antibodies labeled with metallic radionuclides: influence of nuclide chemistry on dose distribution.

An antibody with human CEA specificity has been labeled with either yttrium-90, scandium-47, or indium-111, via a diethylenetriamine pentaacetic acid (DTPA) link covalently bound to the protein. The clearance of these proteins from the blood of mice can be described by a single exponential; the half-life decreases in the order indium-111 greater than yttrium-90 greater than scandium-47. Associated with the blood clearance is an uptake of radioactivity into the liver; scandium-47 has the highest concentration, indium-111 has the least, and yttrium-90 is intermediate. There is no correlation between these results and the equilibrium stability constants of the metals with DTPA-like ligands. The results obtained show that, in vivo, scandium-47 and yttrium-90 are more easily displaced from DTPA by other ions than is indium-111. They also show that free DTPA is able to extract yttrium-90 and scandium-47, but not indium-111, from the liver of treated animals, indicating that indium-111 is resistant to ligand exchange reactions in vivo. These data indicate that 1) the equilibrium stability constant is not a good indicator of the in vivo stability of metal-labeled proteins and 2) it is possible to manipulate the ion distribution and therefore the dose from scandium-47 and yttrium-90 after injection of the labeled proteins.

Animals↗
PubMed1987

General practitioners and alternative medicine.

A questionnaire on the views, beliefs and attitudes of doctors regarding alternative medicine was sent to 274 general practitioners. Of the 222 who replied, 31% said that they had a working knowledge of at least one form of alternative medicine, 29% had read publications on alternative medicine and 41% had attended lectures or classes in alternative medicine. Twelve per cent had received training and 42% wanted further training in an alternative form of medicine; 16% currently practised a form of alternative medicine. The majority of doctors (95%) said that patients had discussed alternative medicine with them during the past year and over half (59%) had referred patients to alternative practitioners. Forty-one per cent of doctors believed that alternative systems of medicine were valid and over half of the doctors (54%) defined alternative medicine as additional to western medicine, not taught in western medical schools or not available on the National Health Service, compared with only 16% who defined alternative medicine as unscientific.

Attitude of Health Personnel↗
PubMed1986

Pharmacokinetics of verapamil in patients with hypertension.

Twelve hypertensive patients (WHO Stage I-II) were given oral verapamil (Isoptin) b.d. or t.d.s. as long-term treatment. The pharmacokinetics of verapamil and norverapamil were studied both after single and b.d. and t.d.s. doses of verapamil 240, 360 or 480 mg daily adjusted according to the blood pressure response. The apparent oral clearance of verapamil was decreased after both the twice and thrice daily dosage regimens (1.38 and 1.841/min, respectively) as compared to the single dose (4.391/min). The plasma half-life of verapamil was increased from 3.34 h (single dose) to 4.65 h (b.i.d.). Decreased elimination of norverapamil was also found after multiple doses of verapamil, as shown by an increase in the adjusted AUC of norverapamil (adjusted to a verapamil dose of 80 mg), namely from 574.9 h X ng X ml-1 (single dose) to 1172 h X ng X ml-1 (b.d.) and to 841 h X ng X ml-1 (t.d.s.). The plasma half-life of norverapamil increase from 5.68 h to 7.34 h during twice daily dosing. During thrice daily verapamil, no increase in plasma half-life was found either for verapamil or norverapamil, probably due to the relatively short sampling time (6 h). The plasma concentration of verapamil and the reduction in supine systolic and diastolic blood pressure were correlated. The mean decrease in supine systolic blood pressure was 5.8 mm Hg per 100 ng verapamil/ml plasma, and for diastolic pressure 2.9 mm Hg per 100 ng verapamil/ml plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1986

Plasma concentrations of codeine and its metabolite, morphine, after single and repeated oral administration.

Plasma concentrations of codeine and its demethylated metabolite, morphine, were determined after single and repeated oral administration of codeine. Twelve healthy volunteers received two doses of codeine 60 mg, 2.8 h apart. In order to achieve steady-state conditions codeine 60 mg was then taken every 8 h for a further five doses. The plasma concentrations of codeine and morphine after the first, second and seventh doses were analyzed by GC-MS. The maximum plasma concentrations of codeine and morphine were reached about 1 h after administration and this time interval did not change on repeated administration. The peak plasma codeine was higher after the second dose of codeine than after the first and the concentration resembled that at steady-state. For morphine, the plasma concentration did not increase significantly after the second dose. Both after a single dose and during steady-state the plasma concentration of morphine was only 2-3% of that of codeine. It seems unlikely that morphine plays a significant role in the analgesic efficacy of single or repeated doses of codeine.

Administration, Oral↗
PubMed1986

Localisation of gastrointestinal cancer with a 131 I labelled monoclonal antibody to CEA.

The localisation of tumour deposits by a 131 I labelled monoclonal antibody to carcinoembryonic antigen (CEA) has been evaluated in 24 patients with primary gastric, oesophageal and colorectal cancer and in 26 patients with clinically suspected recurrent gastric and colorectal cancer. Seventeen of 20 primary sites and 6/15 associated secondary sites were correctly identified by external scanning. Measurement of radiolabelled antibody in the resected specimens demonstrated a 2.6-3.3 fold increase in comparison with the surrounding normal tissue (P less than 0.01). The antibody scans were compared with computerised tomography (CT) in the detection of recurrent disease. The respective sensitivities and specificities for the two investigations were 61% and 33% for antibody scanning and 64% and 100% for CT. Assessment of the distribution of labelled antibody demonstrated rapid clearance with less than 2% detectable in serum samples at 24 h. The implications of these findings together with the mechanisms of excretion are discussed.

Antibodies, Monoclonal↗
PubMed1986

Pharmacokinetics of calcium channel blocking agents.

Verapamil and nifedipine are the most frequently used calcium channel blocking agents in Sweden at present time. The pharmacokinetics of verapamil has been described both in healthy volunteers as well as in patients with supraventricular arrhythmias, angina pectoris, liver cirrhosis, hypertrophic cardiomyopathy or hypertension. Intravenous pharmacokinetics of nifedipine has been investigated in healthy volunteers and oral pharmacokinetics in healthy volunteers as well as in patients with hypertension. The pharmacokinetics of verapamil and of one of its metabolites, norverapamil, is changed after multiple oral dosing as has been described in patients with supraventricular tachyarrhythmias, angina pectoris or in patients with essential hypertension. Plasma concentration-effect relationships have been established for verapamil in different clinical situations and in a few cases also for nifedipine. An update of the pharmacokinetics of these two important calcium channel blocking agents is presented.

Administration, Oral↗