Search PubMed⌕ Search

Biomedical subjects

A White

Publications and source records attributed to A White.

At least 361 records · Page 20Linked to original sources

Clinical or rhinometric assessment of the nasal airway--which is better?

Multiple regression analysis was used to examine the relationship between clinical and rhinometric assessment of the nasal airway and the subjective nasal airway. Clinical examination and rhinometry correlated poorly with the subjective overall nasal airway. Analysis of the data obtained on the differences between the right and the left nasal cavities showed that adding rhinometry did not improve on clinical examination in predicting the patient's subjective sensation of nasal airway.

Humans↗

Modulation of the actions of tyrosine by alpha 2-adrenoceptor blockade.

1. Eight normal subjects were given, in double-blind, random order L-tyrosine 50, 250 and 500 mg kg-1 and placebo orally. Plasma tyrosine concentrations rose in a dose-dependent manner, without affecting the concentrations of the other large neutral amino acids. Tyrosine stimulated the secretion of prolactin and thyrotrophin (TSH) but had no effect on the plasma concentrations of adrenocorticotrophic hormone (ACTH), cortisol, growth hormone or the gonadotrophins. 2. The lack of a stimulant effect of tyrosine on ACTH secretion was presumed to be due to activation of one of the negative feedback mechanisms that control the rate of synthesis and release of the catecholamines, and this hypothesis was tested by examining the effects of the alpha 2-adrenoceptor antagonist idazoxan on the actions of tyrosine. 3. Seven normal males were given on 6 separate occasions tyrosine 250 and 500 mg kg-1 and placebo orally following pretreatment with saline and idazoxan (0.1 mg kg-1 i.v.). Following pretreatment with idazoxan, tyrosine stimulated the secretion of ACTH and noradrenaline in a dose-dependent manner, although neither tyrosine nor idazoxan on their own had any effect on the secretion of either substance. 4. The lack of effect of tyrosine when given on its own appears to be due, to partly, to activation of alpha 2-adrenoceptors, which inhibit the release of noradrenaline. Idazoxan caused a small increase in systolic blood pressure, both when given on its own and in combination with tyrosine. Neither tyrosine nor idazoxan had any significant effect on the state of behavioural arousal, as measured by visual analogue scales, or on the secretion of growth hormone or the gonadotrophins.

Adrenergic alpha-Antagonists↗

Direct measurement of the precursors of adrenocorticotropin in human plasma by two-site immunoradiometric assay.

An immunoradiometric assay (IRMA) for the direct measurement of the precursors of ACTH in unextracted human plasma has been developed and evaluated clinically in normal subjects and patients with disorders of the hypothalamic-pituitary-adrenal axis. The IRMA is based on an iodinated monoclonal antibody to ACTH and a monoclonal antibody to gamma MSH coupled to Sephacryl S300. The assay detects only peptides containing both epitopes, i.e. POMC (31K) and pro-ACTH (22K). The reference standard was partially purified POMC from culture medium of human corticotroph adenoma cells. The detection limit (greater than +2.5SD of the 0 standard) was 2.0 pmol/L and the within-assay coefficient of variation was less than 10% between 29 and 2600 pmol/L. Plasma concentrations of ACTH precursor peptides in 11 normal subjects sampled at 0930 h ranged from 5-34 pmol/L. The concentrations in the patient groups studied were: 260-2300 pmol/L in 5 patients with the ectopic ACTH syndrome associated with small cell lung cancer, less than 2.0-104 pmol/L in 10 patients with pituitary-dependent Cushing's disease, 23 pmol/L in a patient with Nelson's syndrome, and 3.0-230 pmol/L in 5 patients with Addison's disease. We conclude that this IRMA offers a simple and reliable method for measuring ACTH precursors in unextracted plasma. The proportionately greater elevation of ACTH precursors compared to ACTH in patients with the ectopic ACTH syndrome associated with small cell lung cancer but not in pituitary-dependent Cushing's syndrome, suggests that this assay may be clinically useful.

ACTH Syndrome, Ectopic↗

Fused vesical calculi.

A case is described in which a patient, who initially presented with five separate bladder calculi, was found to have had coalescence of three calculi to produce a large stone. This may be one mechanism in the development of a giant vesical calculus.

Aged↗

Immuno-enhancing activity of the amino-terminal domain of human prealbumin: isolation, characterization and synthesis.

A decapeptide isolated from highly purified preparations of human prealbumin was able to restore azathioprine (Az) sensitivity, a property of a sub-class of T-lymphocytes, to the spleen rosette-forming cells (RFC) of adult thymectomized (ATx) mice in vitro. The peptide was sequenced by the Edman method and shown to correspond to the ten amino-terminal residues of prealbumin, Gly-Pro-Thr-Gly-Thr-Gly-Glu-Ser-Lys-Cys. Synthesis of this peptide by solid phase methodology confirmed its activity both in vitro and in vivo. Synthesis of a number of structural analogues indicated that the amino-terminal deca, undeca and dodecapeptides of prealbumin as well as some of their derivatives were also able to restore Az sensitivity to RFC in vitro and in vivo. The Cys10 residue and the Glu7 residues both contributed significantly to potency in vitro. Removal of up to three amino acids from the N-terminus of the decapeptide led to a progressive loss of activity. The data indicates that the ability of human prealbumin to restore the Az sensitivity to the RFC of adult Tx mice is intrinsic to the protein and resides in the amino-terminal domain of the molecule.

Amino Acid Sequence↗

Clinical evaluation of a two-site immunoradiometric assay for adrenocorticotrophin in unextracted human plasma using monoclonal antibodies.

We have developed a sensitive two-site immunoradiometric assay (IRMA) for intact ACTH and its precursors, pro-opiomelanocortin and 22 kDa peptide in unextracted human plasma. The assay uses two monoclonal antibodies. Antibody 1A12, specific for ACTH 10-18, is radiolabelled and antibody 2A3 specific for the C-terminal region (ACTH 24-39), is coupled to Sephacryl S300 for the solid-phase. Samples are incubated for 18 h with labelled antibody followed by 2 h with solid-phase antibody. Separation employs the sucrose layering technique. Using human pituitary ACTH 1-39 (code 74/555) in diluent containing 10% horse serum to standardize the assay, the sensitivity (upper 99% confidence limit of zero standard) is 3.5 +/- 0.8 ng/l (n - 7). The mean coefficient of variation is 5.9% within-assay and 6.7% between-assay and is less than 10% between 22 and greater than 5000 ng/l. Mean recovery of ACTH 1-39 added to dexamethasone-suppressed human plasma is 109% and endogenous ACTH behaves indistinguishably from standard ACTH on dilution. In normal subjects, mean plasma ACTH levels are 30 ng/l at 0730 h, and 15 ng/l at 1630 h at rest. ACTH concentrations are between 60 and 330 ng/l, 8-10.5 h after metyrapone (2 g orally at 2300 h), between 140 and 320 ng/l, 30-60 min after insulin-induced hypoglycaemia, and less than 4 ng/l, 8 h after dexamethasone (1.5 mg orally at 2300 h). In a range of pathological conditions ACTH concentrations accurately reflect the disorders of the pituitary-adrenal axis. Endogenous ACTH immunoactivity is stable in vitro at 22 degrees C for at least 1 h in whole blood and at least 4 h in plasma. It is concluded that this two-site IRMA for ACTH in unextracted plasma offers a reliable assay for clinical purposes.

Adrenal Gland Diseases↗

The nasal cycle and clinical examination of the nose.

A recent study from this department demonstrated the importance of interobserver variation in examination of the nasal airways. Part of this variation may have been due to the mucosal changes of the nasal cycle. We investigated this suggestion and assessed the correlation between anterior rhinometry, a patient questionnaire and 4 different methods of recording the findings of clinical examination. Applying the Kappa statistic we found there was no significant reduction in interobserver variation despite eliminating nasal cycle influence.

Airway Resistance↗

Measurement of corticotropin in unextracted plasma: comparison of a time-resolved immunofluorometric assay and an immunoradiometric assay, with use of the same monoclonal antibodies.

We describe a time-resolved immunofluorometric assay (IFMA) for corticotropin in unextracted human plasma, based on the use of two monoclonal antibodies: europium-labeled antibody 1A12 and antibody 2A3 coated onto microtiter wells. We compared the results of this assay with those of an immunoradiometric assay (IRMA) performed with the same antibodies working ranges (CV less than 10%) were 25 to 1000 ng/L and 22 to 1000 ng/L for the IFMA and IRMA, respectively, and both assays had comparable detection limits (IFMA 4.0 +/- 1 ng/L, IRMA 3.5 +/- 0.8 ng/L). Results by both assays for 130 patients' samples containing corticotropin within the range 3-100 ng/L and greater than ng/L correlated well (r = 0.88 and 0.92, respectively), and samples with corticotropin in the range 80-624 ng/L gave results that paralleled those for the standard curve. Corticotropin concentrations in apparently healthy subjects were consistent with those reported previously. The IFMA is a simple, precise, and robust assay that can be completed within one day. Its nonisotopic label is stable for at least 50 weeks.

Adrenocorticotropic Hormone↗

Solid-phase radioimmunoassay for IgG antibodies to Staphylococcus epidermidis. Use in serious coagulase-negative staphylococcal infections.

A radioimmunoassay (RIA) for human IgG antibodies to Staphylococcus epidermidis was compared with an agar-gel-diffusion assay in patients with a variety of infections. The RIA was sensitive and reproducible and discriminated between endocarditis and uncomplicated bacteremias due to coagulase-negative staphylococci. Anti-S epidermidis antibodies by RIA were elevated in 16 (89%) of 18 patients with coagulase-negative staphylococcal endocarditis but in none of 28 patients with uncomplicated bacteremia (n = 18) or with blood culture contaminated with these organisms (n = 10). Cross-reacting IgG antibodies to S epidermidis antigens were also detected by RIA in 13 (76%) of 17 patients with Staphylococcus aureus endocarditis but in none of 17 patients with nonvalvular S aureus bacteremias and in none of 25 patients with endocarditis or bacteremia caused by other pathogens. Agar-gel-diffusion assay was less sensitive than RIA for detecting coagulase-negative staphylococcal endocarditis, being positive in nine (50%) of 18 such patients. This RIA may be useful in distinguishing patients with endocarditis from those with nonvalvular staphylococcemias or blood culture contamination.

Antibodies, Bacterial↗

Pitfalls in the assessment of dysphagia by fibreoptic oesophagogastroscopy.

We present a paper to highlight that the investigation of dysphagia by the standard methods of barium swallow and the now routinely used fibreoptic oesophagogastroscope may miss or inadequately assess pharyngeal and hypopharyngeal causes of dysphagia and to remind that if such a cause is suspected then rigid endoscopy is required to assess or exclude the pathology.

Aged↗

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↗

Characterisation of monoclonal and polyclonal antibodies to 19-linked conjugates of testosterone with corresponding radioligands.

Monoclonal antibodies to testosterone T were produced using testosterone 19-O-carboxymethyl ether (T19C) and testosterone 19-hemisuccinate (T19H) immunogens. All antibodies were characterised with iodinated derivatives of both T19C and T19H. Monoclonal antibodies derived from the T19C immunogen had similar titres and assay sensitivities with both T19-tracers. In contrast antibodies derived from the T19H immunogen bound the homologous but not the heterologous tracer. Individual antibodies showed a wide variation in cross-reactivity with 5 alpha-dihydrotestosterone, DHT (4.4-100%), androstenedione AN (0.5-100%) and progesterone, Po (0.08-5.4%). One antibody 3F11 derived from a T19C immunogen gave 50% displacement of tracer with 180 pgT/tube and low cross-reactivity of 12% with DHT, 3.0% with AN and 1.1% with Po. In general, assay sensitivity and antibody specificity were poorer with an [125I]-histamine conjugate of T-3-carboxymethyloxime than with T19 tracers. Radioimmunoassays for T in extracted human serum were developed with [125I]T19C as tracer and monoclonal antibody 3F11 (T19C immunogen) and rabbit antiserum T19H3R1 (T19H immunogen). Sensitivities of the extracted assays were 43 and 20 pg/tube respectively and results correlated well with those obtained after chromatographic separation of testosterone (r = 0.97 for both antibodies). We conclude that 19-linked derivatives of T are highly immunogenic for the production of specific testosterone antibodies. Selection of the appropriate iodinated tracer is essential to achieve optimal titre, assay sensitivity and specificity, since these characteristics vary widely with individual monoclonal antibodies, and classical bridge recognition is not observed.

Androstenedione↗

Serum cortisol, glucose and lipids in plaice (Pleuronectes platessa L.) exposed to starvation and aquarium stress.

Plaice were maintained in the aquarium (11-12 degrees C) during May for 15 days without feeding. Within 48 hr, there was a decline in serum total lipids (P less than 0.001), phospholipids (P less than 0.01), triglycerides (P less than 0.001), cortisol (P less than 0.01) and glucose (P less than 0.001), but an increase in nonesterified fatty acids (NEFA; P less than 0.01). There was a significant inverse correlation between NEFA and glucose over 15 days (P less than 0.001) and between NEFA and cortisol over the first 5 days (P less than 0.01). Cortisol and glucose showed a significant correlation over 15 days (P less than 0.01). Serum cortisol and glucose were not apparently affected by starvation. Only cortisol provided a sensitive indicator of aquarium disturbance. Exposure of the fish to agitation or reduced O2 for 1 hr significantly elevated cortisol (P less than 0.001) but only the latter treatment elevated glucose (P less than 0.01); neither treatment affected the lipids.

Animals↗