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Biomedical subjects

G Caldwell

Publications and source records attributed to G Caldwell.

At least 19 recordsLinked to original sources

Near visual acuity: a simple measure of practical significance in insulin-treated diabetic patients.

The value of measuring near visual acuity as a predictor of loss of independence in administering insulin and monitoring blood or urine glucose has been assessed in 110 insulin-treated diabetic patients. Near visual acuity was simple to measure in the clinic setting, and correlated well with 6 m acuity. Fourteen patients depended on an assistant either to draw up the correct dose of insulin (n = 12), inject the insulin (n = 7) or to monitor blood or urine glucose (n = 12). Of these 14 patients only one, who was demented, had near visual acuity better than N.12. Two other patients had near visual acuity N.12 or worse and yet were independent of help. One had severe visual impairment and used a pen-injector and a meter with speech synthesizer, and the other had near visual acuity of N.12. Impairment of near visual acuity to N.12 or worse is associated with loss of independence in insulin-treated diabetes. Measurement of near visual acuity could be useful in predicting independence of insulin-treated patients.

Blood Glucose Self-Monitoring

Retinal blood flow following a tyramine-induced increase in blood pressure.

The effect of increasing systemic blood pressure on retinal blood flow was investigated in anaesthetised miniature pigs. Blood pressure was increased by the infusion of the sympathomimetic amine, tyramine. Volume flow was determined from axial erythrocyte velocity, measured by laser Doppler velocimetry, and vessel diameter, measured from monochromatic retinal photographs. Measurements were taken when mean arterial pressures were elevated by a mean of 22 +/- 3% and 50 +/- 8% above resting values, which represented increases of 31 +/- 2% and 74 +/- 16% in ocular perfusion pressures. Retinal blood flow increased by 8.5 +/- 8% at the lower infusion rate and by 57 +/- 19% at the higher infusion rate. We conclude that tyramine infusion is a suitable method for the study of retinal autoregulation and that the upper limit of retinal autoregulation in miniature pigs lies between 22-50% above resting mean arterial pressure.

Animals

A laser Doppler velocimetry study of the effect of hypoglycaemia on retinal blood flow in the minipig.

The effect of acute hypoglycaemia (plasma glucose less than 2.2 mmol/l) on retinal venous blood flow in the minipig has been determined using bidirectional laser Doppler velocimetry and red free retinal photography. In six pigs the mean flow in a retinal vein increased from 19.3 (+/- 2.8 SEM) microliters/min to 29.7 (+/- 7.5) microliters/min during hypoglycaemia (p less than 0.05) with a return to 18.6 (+/- 3.6) microliters/min when euglycaemia was restored. Retinal blood flow is affected by hypoglycaemia or its haemodynamic consequences.

Animals

Long-term outcome after photocoagulation for proliferative diabetic retinopathy.

One-hundred and forty patients with 182 treated eyes were followed for up to 10 years after photocoagulation for proliferative diabetic retinopathy. Sixty-eight patients were still alive and under review after 10 years. Mortality was 33% at 10 years and the survivors were younger when treated and had lower systolic and diastolic blood pressures, a lower urea and creatinine and a lower prevalence of proteinuria and ECG evidence of ischaemia at baseline. Sixty-nine percent of all patients and 82% of those followed up for 10 years maintained good vision (6/12 or better) in their better eye at the last follow-up. Visual deterioration occurred mostly in the first 2 years after treatment and risk factors for poor final vision were poor vision at baseline, severity of disc new vessels, and age at presentation. It is concluded that the short-term beneficial effect of photocoagulation is maintained over long periods of follow-up.

Adult

Intracellular mechanisms involved in the stimulation of growth hormone release from rat anterior pituitary cells by Russell's viper venom.

We have previously shown that a heat-stable component of Russell's viper venom (RVV) releases GH in a dose-dependent manner from cultured rat anterior pituitary cells. We have now investigated the intracellular mechanisms involved in RVV-stimulated GH release by concomitant administration of RVV with known intracellular mediators in rat pituitary cells. 3-Isobutyl-1-methylxanthine (IBMX; 0.5 mmol/l), added to cultured rat anterior pituitary cells simultaneously with RVV, at concentrations up to a maximally effective dose of 10 micrograms/ml, increased GH release (3.7-fold, 4.0-fold and 2.0-fold; P less than 0.001) compared with the effect of venom alone. These effects were additive, indicating that RVV and IBMX stimulate through different intracellular messengers. RVV failed to increase the formation of basal or IBMX-stimulated intracellular cyclic AMP (cAMP), confirming that RVV affects GH release through a cAMP-independent pathway. 12-0-Tetradecanoylphorbol-13-acetate (TPA; 0.1 mumol/l), added simultaneously with various doses of RVV (0.1-10 micrograms/ml), did not increase GH release beyond the maximal effect of RVV. This result indicates that RVV might be stimulating GH release through a similar mechanism to that of TPA (by activating protein kinase C). When pituitary cells were perifused with Ca(2+)-free medium or verapamil (50 mumol/l), RVV-stimulated GH release was inhibited by 65 and 42% respectively. This reflects the recognized requirement of Ca2+ for secretory processes. However, RVV (10 micrograms/ml) had no significant effect on intracellular free Ca2+ concentrations as measured using the fluorescent Ca2+ probe quin-2.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine

Retinal blood flow during hyperglycemia. A laser Doppler velocimetry study.

The effect of different rates of glucose infusion on the retinal circulation was studied in Gottingen breed minipigs. Seven minipigs were made hyperglycemic rapidly with an intravenous bolus injection of 50% dextrose, after which a slow dextrose infusion maintained hyperglycemia for 60 minutes. Seven minipigs were more gradually made hyperglycemic over 60 minutes with a slow intravenous infusion of 50% dextrose, and a further seven had a control infusion of urea of equal volume and osmolality over 60 minutes. Retinal blood flow (RBF) was determined from the maximum (centerline) velocity of the blood (Vmax) (determined by bidirectional laser doppler velocimetry) and the vessel diameter (D) (determined from monochromatic fundus photographs). Measurements were made in a single temporal retinal vein of each animal at baseline, during, and after each of the infusions. Plasma glucose rose from 6.1 +/- 0.5-25.3 +/- 1.5 mM (mean +/- standard error) during the bolus infusion and from 6.4 +/- 0.7-22.0 +/- 0.7 mM during the slow infusion. The bolus and the slow glucose infusions both produced large increases in RBF (63% and 62%, respectively) which were mainly attributable to increases in Vmax. The urea infusion had no significant effect on RBF, Vmax, or D. The ocular perfusion pressure rose slowly and was significantly elevated after 60 minutes of slow glucose infusion but not after the urea infusion.

Animals

Different hepatic responses to thyroxine replacement in spontaneous and 131I-induced primary hypothyroidism.

The serum levels of a range of analytes known to change with thyroid status were measured in two groups of patients with primary hypothyroidism commencing T4 replacement therapy. One group (group 1; n = 9) had spontaneous hypothyroidism whilst in the second (group 2; n = 10), hypothyroidism had resulted from radioiodine therapy. The replacement dose was increased in 50 micrograms increments each month to 200 micrograms/day; this produced similar serum concentrations of thyroid hormones and TSH in the two groups at each dose. Dose-dependent increases in glutathione S-transferase (GST) were seen in both groups but changes in alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) activities occurred only in group 1 patients. Group 1 patients had significantly higher levels of GST than group 2 at the 150 micrograms (P less than 0.01) and the 200 micrograms (P less than 0.005) doses of T4, and they had higher activities of ALT (P less than 0.01) and GGT (P less than 0.02) at the 200 micrograms dose. Seven patients in group 1 had abnormalities in GST and four had high levels of ALT, whereas three patients from group 2 had high GST concentrations and all had ALT activities within reference limits. The concentrations of the other analytes measured in serum showed the same response to T4 in the two groups, particularly the concentrations of certain transport proteins whose serum concentrations depend on hepatic protein synthesis. These data suggest that patients with spontaneous primary hypothyroidism are more susceptible to hepatocellular damage than patients who have radioiodine-induced primary hypothyroidism when given oral doses of thyroxine greater than 150 micrograms/day.

Adult

Resistant hyperthyroidism induced by sodium iopodate used as treatment for Graves' disease.

Sodium iopodate has recently been advocated for long-term control of hyperthyroidism in Graves' disease. Its advantages over conventional therapy are a rapid fall in thyroid hormones and control of symptoms with a simple dosage regime. We report a case in which severe resistant hyperthyroidism developed during treatment of Graves' disease with sodium iopodate. Sodium iopodate may not be suitable for long-term use in all patients with Graves' disease.

Adult

Growth hormone-releasing factor-induced growth hormone secretion from perifused rat anterior pituitary cells: lack of influence of glucose concentration, and normal responses in pituitary cells from diabetic animals.

The mechanism responsible for the suppression of GH secretion in hyperglycaemia and hypoglycaemia in rats has been investigated using perifusion of anterior pituitary cells. When perifused with Krebs-Ringer bicarbonate containing normal (5 mmol/l), high (20 mmol/l) and low (1 mmol/l) concentrations of glucose, the GH responses to GH-releasing factor (GRF) were 85 +/- 5, 85.5 +/- 5.4 and 89 +/- 3.0 (S.E.M.)% respectively compared with the initial response to GRF at 5 mmol/l in each column. The mean GH response to GRF from anterior pituitary cells of normal rats was 6.58 +/- 0.88 micrograms/three pituitaries, which was not statistically different form that of cells from rats with streptozotocin-induced diabetes (5.40 +/- 0.68 micrograms/three pituitaries). It is concluded that GH suppression in diabetic rats and during hypoglycaemia is not mediated by changes in the GH response to GRF.

Animals

Restoration of normal thyrotrophin secretion reduces the abnormally high serum glutathione S-transferase levels found in patients receiving thyroxine replacement therapy.

The peripheral tissue thyroid status of 12 patients receiving thyroxine replacement therapy was investigated both when pituitary secretion of TSH was suppressed and later, when on a lower dose of thyroxine that restored thyrotroph responsiveness. Heart rate and various analytes in serum known to be sensitive to thyroid status were measured in addition to TSH by immunoradiometric assay. Initially, the serum T4 concentration was raised in seven patients and free T4 raised in nine; all patients had normal T3 concentrations. Later, on the lower dose of thyroxine, most patients had concentrations of thyroid hormones within reference limits. Concentrations of the liver-specific form of glutathione S-transferase (GST) in serum decreased (P less than 0.01) after the reduction in thyroxine dose; abnormally high GST levels, found in eight patients when TSH was suppressed, returned to normal in six of these patients when normal basal and TRH-stimulated TSH concentrations had been restored. The response of the pituitary to excess thyroxine may be more representative of other tissues (e.g. the liver) than previously thought.

Adult

Laboratory and diagnostic performance of a coated well immunoradiometric assay for serum thyrotrophin.

A new, coated well immunoradiometric assay (IRMA) for thyrotrophin (TSH) in serum has been evaluated with a view to its use as a first-line test of thyroid function. The Amerwell TSH IRMA is simple, rapid to perform (2.5 h) and the assay sensitivity was 0.07 mU/L with a working range (intra-assay CV less than 10%) of 0.3-100 mU/L. The mean inter-assay CV was 6.6% for TSH concentrations of 0.30-30.7 mU/L. The method compared favourably with an in-house TSH radioimmunoassay and an alternative commercial IRMA. In consecutive referrals to a thyroid clinic all patients with overt hyperthyroidism (n = 103) had undetectable TSH concentrations and in those with subclinical hyperthyroidism (n = 14). TSH was undetectable in 10 and below the reference range in four. The 95% confidence interval for 63 euthyroid serum samples was 0.36-4.3 mU/L. All hypothyroid patients (n = 20) had increased TSH concentrations. TSH concentrations in pregnancy did not differ significantly from euthyroid TSH values. From 1916 routine tests, 13 undetectable TSH values were found in which thyroid hormone levels were normal and the patients had no known thyroid disorder. The assay appears suitable as a first-line test of thyroid function, but further assessment in a routine laboratory setting is required.

Humans

Relationship between pituitary and other target organ responsiveness in hypothyroid patients receiving thyroxine replacement.

This study was undertaken to compare the sensitivity of the thyrotrophs to that of other tissues to T4 treatment in hypothyroid patients. To do so, we measured serum total and free thyroid hormones and TSH, in addition to several serum markers of peripheral tissue response to thyroid status, in 21 hypothyroid patients treated with 50-micrograms increments of T4 to a maximum of 200 micrograms daily (group I) and in 104 clinically euthyroid patients receiving a long term constant replacement dose (group II). In group I patients, dose-dependent increases (P less than 0.05) in serum glutathione S-transferase, sex hormone-binding globulin, and angiotensin-converting enzyme occurred, whereas serum T4-binding globulin, creatine kinase, and creatinine levels decreased (P less than 0.05). In both patient groups, abnormally high levels of glutathione S-transferase, sex hormone-binding globulin, angiotensin-converting enzyme, alanine aminotransferase, and gamma-glutamyl transferase were found in some patients during treatment. One or more of these biochemical abnormalities suggestive of hyperthyroidism occurred in 15 (71%) group I patients and 27 (26%) group II patients. These were associated with an undetectable serum TSH (less than 0.1 microU/ml) and raised free T4 concentrations in 13, and raised free T3, T4, and T3 concentrations in only 8, 6, and 1 group I patients, respectively. In group II patients, they were more closely associated with an undetectable TSH (67%) or raised free T4 (85%) level than with raised concentrations of free T3 (33%), T4 (26%), or T3 (0%). The use of high sensitivity TSH assays will permit more accurate adjustment of T4 replacement and minimize abnormalities in peripheral tissue biochemistry indicative of overtreatment.

Adolescent

Value and limitations of a highly sensitive immunoradiometric assay for thyrotropin in the study of thyrotroph function.

Using a highly sensitive and specific immunoradiometric assay for thyrotropin, we studied thyrotroph function in 232 new patients referred to a thyroid clinic and in 13 patients after treatment for hyperthyroidism. Significant thyrotroph responsiveness to thyroliberin (thyrotropin-releasing hormone, TRH) was found in all patients with values for basal thyrotropin greater than 0.1 milli-int unit/L. In no overtly hyperthyroid patient was any increment in thyrotropin recorded at 20 min after thyroliberin administration. In seven patients, four subclinically hyperthyroid and three who had received treatment, increments in thyrotropin from undetectable basal values were recorded, consistent with incomplete thyrotroph suppression. By use of assays with even higher sensitivity, one may be able to distinguish these patients from overtly hyperthyroid patients.

Adolescent

Fasting hyperinsulinemic hypoglycemia after ritodrine therapy for premature labor.

A 26-year-old woman with a triplet pregnancy was treated prophylactically with ritodrine beginning at 15 weeks' gestation. At 32 weeks, she was admitted in preterm labor, and over the next 12 days received high-dose oral or intravenous ritodrine. Three female infants were delivered by cesarean section after spontaneous rupture of the membranes. Postoperatively, she developed profound hypoglycemia with inappropriately high insulin levels. Maternal hypoglycemia after ritodrine therapy in pregnancy has not been reported previously. We discuss possible mechanisms.

Adult

An improved approach to thyroid function testing in patients with non-thyroidal illness.

We have compared the results of serum thyrotrophin (TSH) measurements using a sensitive immunoradiometric assay (IRMA) with those of conventional thyroid function tests in 299 hospital inpatients with a range of non-thyroidal illnesses. Levels of total thyroxine (T4), free T4, total tri-iodothyronine (T3) and free T3 in the hypothyroid range were recorded in 8%, 15%, 19% and 49% of patients, respectively, whereas TSH (IRMA) was abnormally low in 1%. Furthermore, basal TSH (IRMA) accurately predicted the result of the thyrotrophin-releasing hormone test in 72 of the 74 patients in whom this test was performed and, unlike thyroid hormone measurement, identified patients with subclinical thyroid disease. It would appear that a single basal TSH (IRMA) measurement is the most appropriate screening test for thyroid dysfunction in patients with concomitant acute or chronic illness.

Adolescent

Two concurrent epidemics of enteroviral meningitis in an obstetric neonatal unit.

A small epidemic of viral infection occurred in a neonatal unit. It involved 11 infants, all of whom recovered. Echovirus 11 was the cause of illness in six infants, coxsackie B3 in four, and one infant had a biphasic illness, due first to echo 11, then to coxsackie B3. The epidemic coincided with a major outbreak of echovirus 11 and a smaller outbreak of coxsackie B3 in the community. Several staff became ill. Five infants were considered to have been infected by perinatal materno-infant spread, others by cross-infection. The epidemic ended when the nursery was closed.

Australia

SimulTRAC simultaneous radioimmunoassay of thyrotropin and free thyroxin evaluated.

We assessed the analytical and diagnostic performance of a dual-isotope RIA for thyrotropin (TSH) and free thyroxin (FT4) in serum. The mean interassay CVs for these analytes were 7.9% and 5.0%, respectively. The mean minimum detection limit for TSH was 0.25 milli-int. unit/L, the mean analytical recovery 110%. There was good agreement with values for TSH and FT4 measured by alternative RIA procedures. Euthyroid patients were well distinguished from those with overt thyroid disease, although there was a small overlap in the case of TSH. Combining the two results better discriminated these categories and identified those patients with subclinical thyroid disease who had abnormal TSH concentrations but FT4 concentrations within reference limits. Euthyroid women taking estrogen-containing oral contraceptives had normal results for TSH and FT4, as did most pregnant women studied. During the third trimester of pregnancy, TSH concentrations of women with low FT4 concentrations were within reference limits. Similarly, euthyroidism was confirmed in patients with low FT4 due to nonthyroidal illness by the simultaneous finding of a normal TSH concentration.

Adult