PubMed HealthSearch

Biomedical subjects

G A Edwards

Publications and source records attributed to G A Edwards.

At least 19 recordsLinked to original sources

The impact of recent advances in diagnostic technology on the clinical presentation of phaeochromocytoma.

OBJECTIVE: To examine the impact of recent advances in diagnostic technology on the spectrum of clinical and biochemical features of patients presenting with a new diagnosis of phaeochromocytoma. DESIGN: A retrospective review of the clinical and biochemical features of patients diagnosed by our laboratory as having phaeochromocytoma within a 27-month period up to December, 1990. Noradrenaline, adrenaline and dihydroxyphenylglycol were assayed in 24-hour urine specimens (19 patients) or plasma (1 anuric patient) by gas chromatography/mass spectrometry. SETTING: A tertiary level chemical pathology department. PATIENTS: Twenty patients with a new diagnosis of phaeochromocytoma. RESULTS: The classic, episodic adrenergic symptoms traditionally associated with phaeochromocytoma were absent in 9 of the 20 patients (45%). "Atypical" phaeochromocytoma presented as a mass on computed tomography imaging (6 patients, 30%), "phaeochromocytoma crisis" (4 patients, 20%) or family screening (1 patient, 5%). Excessive adrenaline production was found in 11 patients (55%) and six (30%) had predominantly adrenaline-secreting tumours. The urinary noradrenaline:dihydroxyphenylglycol ratio was raised in all nine patients with predominantly noradrenaline-secreting tumours but was not raised in nine out of ten patients with adrenaline-secreting phaeochromocytoma. Adrenaline excretion was significantly correlated with tumour size (r = 0.8; P less than 0.05). CONCLUSIONS: Advances in diagnostic technology, particularly specific adrenaline assays and computed tomography, have made possible the early diagnosis of patients with phaeochromocytoma presenting in ways previously thought to be uncommon. All patients with adrenal masses noted incidentally on CT scan should be investigated for phaeochromocytoma. Adrenaline-secreting tumours are common and both noradrenaline and adrenaline should be assayed in all patients investigated for phaeochromocytoma.

Adrenal Gland Neoplasms

Activation of P1- and P2Y-purinoceptors by ADP-ribose in the guinea-pig taenia coli, but not of P2X-purinoceptors in the vas deferens.

1. The activity of adenosine 5'-diphosphoribose (ADP-ribose), a ribosylated purine nucleotide, was investigated on the carbachol-contracted taenia coli, a tissue possessing P1- (A2) and P2Y-purinoceptors and on the guinea-pig vas deferens which possesses P2X-purinoceptors. 2. In the vas deferens, where ATP (1 microM-1 mM) produced concentration-dependent contractions, ADP-ribose was without effect at concentrations up to 1 mM. 3. In the taenia coli, ADP-ribose (0.1 microM-1 mM) produced concentration-dependent relaxations with a potency similar to that of adenosine, but less than that of ATP. The pD2 values for ADP-ribose, adenosine and ATP were 4.5 +/- 0.07 (27), 4.4 +/- 0.10 (9) and 5.5 +/- 0.14 (21), respectively. The time-course of the relaxations elicited by ADP-ribose was found to be significantly longer than that for ATP and significantly shorter than that for adenosine. 4. The P1-purinoceptor antagonist, 8-phenyltheophylline (5 microM), produced parallel rightward shifts in the concentration-response curves of the relaxations of the taenia coli elicited by ADP-ribose and adenosine but not ATP. 5. Dipyridamole (0.3 microM), a purine nucleoside uptake inhibitor, potentiated the responses to adenosine and ADP-ribose in the taenia coli. These potentiations were sensitive to 8-phenyltheophylline (5 microM). 6. Reactive blue 2, a P2Y-purinoceptor antagonist, antagonized the inhibitory responses of ADP-ribose and ATP in the taenia coli, without significantly altering the inhibitory responses of either adenosine or noradrenaline.7. In the presence of the potassium channel blocker, apamin (0.3 microM), the inhibitory responses of ADP-ribose were severely attenuated, and the inhibitory responses of ATP in the taenia coli were converted to transient contractions. Further addition of 8-PT blocked the residual responses of ADPribose.8. The P2-purinoceptor antagonist, suramin (500 microM), antagonized responses to ATP and ADP-ribose,but not adenosine. Further addition of 8-PT antagonized the residual responses to ADP-ribose, but not to ATP.9. It is concluded that ADP-ribose has a mixed pharmacological profile, evoking both PI (A2)-purinoceptor-mediated responses and P2Y-purinoceptor-mediated responses, while being inert at P2Xpurinoceptors.It is suggested that ADP-ribose may provide a useful starting point for the generation of structural analogues which have specific activity at the P2Y-purinoceptor.

Adenosine Diphosphate Ribose

Pea lectin is correctly processed, stable and active in leaves of transgenic potato plants.

A gene encoding the preproprotein of the pea (Pisum sativum) lectin was expressed in transgenic potato plants using a cauliflower mosaic virus (CaMV) 35S promoter or a tobacco ribulose bisphosphate carboxylase small subunit (ssRubisco) promoter. Presence of the pea lectin to levels greater than 1% of total soluble leaf protein was detected by radioimmunoassay (RIA). The pattern of expression derived from the two promoters was established using both RIA and a squash-blot immunolocalisation technique. Western blotting demonstrated that the preproprotein was correctly processed, generating alpha and beta subunits that assembled to give an isolectin form observed in pea seeds and roots. It was also found that the haemagglutination activity and specificity of pea lectin synthesised in transgenic potato leaves was comparable to purified lectin from pea cotyledons.

Animals

Evaluation of three theophylline dosing methods in pediatric patients.

Three methods used for individualizing theophylline dosing were prospectively evaluated in 34 pediatric patients to compare the methods' ability to accurately predict steady-state serum theophylline concentrations (STCs) from non-steady-state data. Methods evaluated included a Bayesian weighted sum of squares regression program, an algebraic method developed by Chiou, and a commonly used population-based pediatric dosing algorithm. An expanded retrospective evaluation was also done to further compare the Bayesian and Chiou methods. Patients (aged 1-11 y) admitted to the hospital for acute bronchospasm refractory to inhaled beta agonists and with physician's orders to receive intravenous aminophylline were eligible for participation. Study patients received a 6-mg/kg loading dose aminophylline, followed by a 0.8-1.0 mg/kg/h constant aminophylline infusion. STCs were obtained 0.5 and 5.5 hours postinfusion. Subjects were randomized to one of three dosing method groups (Bayesian, Chiou, or pediatric algorithm). Doses were calculated using the assigned method to attain a target steady-state STC. Predictions from each dosing method were compared with actual serum concentrations for bias and precision. Additionally, analysis of fit-to-the-line-of-identity for predicted versus observed STCs was evaluated for each method. Precision of methods was also compared with regard to their ability to predict within 20 percent of their observed steady-state STC. Results from the prospective evaluation showed no significant difference between the three methods tested. Predicted STCs fell within 20 percent of their observed steady-state concentrations for 18 percent (2/11) of patients in the algorithm group, and 45 percent (5/11) of patients in the Chiou group and 17 percent (2/12) of the patients in the Bayesian group met this criterion. Retrospective analysis of all 34 patients demonstrated that the Bayesian and Chiou methods had similar bias and precision and no statistical difference was found between them. The results from this evaluation suggest that the pediatric dosing algorithm is equivalent in predictive bias and precision to the Bayesian and Chiou methods as well as in its ability to identify doses that result in steady-state STCs within 20 percent of their target values. Given the relative inaccuracy of these methods, cautious use of these techniques is recommended when evaluating non-steady-state STCs obtained from children during the acute stages of reactive airway disease.

Algorithms

Renal handling of phosphate following release of ureteral obstruction.

The handling of phosphate by the kidney following release of unilateral ureteral obstruction (UUO) was investigated in intact and thyroparathyroidectomized (TPTX) dogs, and compared to that in the kidney following unilateral release of bilateral ureteral obstruction (BUO). By contrast to the kidney after release of BUO, the kidney following release of UUO showed a much lower fractional excretion (FE) of phosphate in TPTX animals (BUO 21.5 +/- 6.8%; UUO 1.3 +/- 0.5%) and a blunted phosphaturic response to PTH (BUO delta + 25.8%; UUO delta + 2.6%). Administration of cyclic AMP, prostaglandin synthetase inhibitors and ammonium chloride failed to correct the hypophosphaturia or the blunted response to PTH. Raising the filtered load of phosphate, however, raised the FE of phosphate in TPTX dogs in the kidney after release of UUO to levels comparable to those in BUO (BUO 21.5 +/- 6.8%; UUO 21.8 +/- 5.1%) and restored the responsiveness to PTH (BUO 49.0 +/- 8.2%; UUO 39.7 +/- 10%). When reabsorptive capacity (RC) was calculated during stepwise increments of serum phosphate, an additional difference was identified between the kidney after release of UUO on the one hand, and the control kidney and the kidney after release of BUO on the other: RC for phosphate was 294 +/- 66 micrograms/min . kg in UUO, 130 +/- 16 micrograms/min . kg in control, and 62 +/- 19 micrograms/min . kg in BUO. It is concluded that, in addition to the role of reduced filtered load of phosphate, an increased capacity to reabsorb phosphate is responsible in part for the hypophosphaturia observed in the kidney following release of UUO.

Ammonium Chloride

The mental illness of Captain Hyndman.

The mental illness of Captain Charles Robertson Hyndman resulted in his compulsory hospitalization in Tarban Creek Asylum in 1843 and 1864-1866. His illness, and the question of mental health law which was subsequently raised, were of great significance for the colony of New South Wales in that it led to the first specific lunacy legislation in the state. The issues raised are still the fundamental questions with which contemporary mental health law is concerned.

Adult

High-altitude pulmonary edema in children.

A 15-year-old boy with recurrent high-altitude pulmonary edema had previously been mistakenly treated for asthma and pneumonia. Clinical manifestations of this disorder, its etiology, treatment, and prevention are discussed.

Acclimatization

Effectiveness of low-dose continuous intravenous insulin infusion in diabetic ketoacidosis. A prospective comparative study.

Twenty pediatric patients with diabetic ketoacidosis were randomly assigned in equal numbers to receive insulin either as a low-dose continuous intravenous infusion or as high-dose intermittent subcutaneous injections. Blood was obtained hourly for determinations of total CO2, plasma glucose, and osmolality, and, in previously untreated patients, plasma insulin. Serum values of beta hydroxybutyrate, electrolytes, and acetone were monitored every two hours. Plasma insulin levels were in the therapeutically effective range with each method of administration. There were no statistically significant differences in rate of correction of ketoacidosis, rate of reduction of plasma glucose, or decline in plasma osmolality. The incidence and the severity of hypokalemia were increased in the patients receiving subcutaneous insulin. There was less variation in the rate of reduction of plasma glucose in the infusion group. Low-dose continuous intravenous infusion of insulin is at least as effective in treating diabetic ketoacidosis as the traditional high-dose intermittent subcutaneous injection of insulin and offers some definite advantages.

Adolescent

Formation of methionine from alpha-amino-n-butyric acid and 5'-methylthioadenosine in the rat.

Adult rats may utilize two metabolites of methionine for the biosynthesis of this essential amino acid. In separate experiments methionine, labeled with 14C or with 35S was observed in plasma and urine following the administration of [2-14C]-alpha-amino-n-butyric acid or [35S]-5'-methylthioadenosine by stomach tube. Although alpha-amino-n-butyric acid (ABA) or homoserine, alone or with dietary sodium sulfate, choline, and/or S-methylcysteine, was not utilized for growth, weight loss in weanling rats was decreased by dietary cysteine when fed as an additive to a basal methionine-free, cysteine-free, labile methyl-free, sulfur-free diet. Following the addition of 10 mg ABA and 28 mg 5'-methylthioadenosine/day to the basal diet, growth response was equivalent to that occurring in rats receiving 27 mg of methionine/day with the basal diet. The implications of these findings for adaptation to protein restriction and a discussion of equilibrium and steady state conditions related to the increase in methionine content in the blood are presented.

Adenosine

Cataracts in bleomycin-treated rats.

Bleomycin was administered to 126 normal or human-tumor-bearing baby rats we observed for the development of cataracts. Eighty-four percent of the rats receiving this drug before the age of 10 days developed lens opacities. Bleomycin given to 10-day-old rats or older did not induce cataract formation. The cataracts initially occurred in the nuclear area and later involved most of the lens whether or not bleomycin was later discontinued. The presence of the tunica vasculosa lentis in rats younger than 10 days old may explain why cataracts developed only in these young animals.

Age Factors