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T W Jones

Publications and source records attributed to T W Jones.

At least 37 records · Page 2Linked to original sources
PubMed1998

Hypoglycemia in children with diabetes: incidence, counterregulation and cognitive dysfunction.

Hypoglycemia remains a critical problem in the treatment of IDDM and often limits our ability to consistently achieve excellent glycemic control. Ongoing studies will be important to increase our understanding of the factors responsible for its occurrence and the impact that hypoglycemia may have, particularly for the brain. Significant differences have been documented between adults and children in the incidence of this complication of insulin therapy as well as in the counterregulatory hormone responses to hypoglycemia and its effects on the CNS. While children with diabetes still need insulin treatment, the prevention of hypoglycemia will be a central aim of management. This will depend on effective and expert diabetes education and support for the patient and his or her family along with better efforts to achieve more physiological insulin replacement.

Adolescent↗
PubMed1998

Comparison of human regular and lispro insulins after interruption of continuous subcutaneous insulin infusion and in the treatment of acutely decompensated IDDM.

OBJECTIVE: To compare the rapidity of metabolic decompensation after interruption of CSII between human regular and lispro insulin and to compare these two insulins in the correction of the hyperglycemia and ketosis of mildly decompensated IDDM. Lispro insulin may be especially useful for insulin pump therapy (continuous subcutaneous insulin infusion [CSII]). RESEARCH DESIGN AND METHODS: A total of 18 patients with well-controlled IDDM (HbA1c 7.7 +/- 1.1%, age 30 +/- 11 years) were studied. All were being treated with CSII (nine with human regular and nine with lispro insulin). The study consisted of two phases: 1) an insulin interruption phase, in which the basal insulin infusion was stopped (at 0300) and plasma insulin, glucose, and beta-O-hydroxybutyrate (beta-OHB) were measured every 15-60 min for 6 h after interruption of the insulin infusion and 2) an insulin replacement phase, which involved measuring plasma insulin, glucose, and beta-OHB for 2 h after a single injection of either human regular or lispro insulin to correct the hyperglycemia and ketosis that developed during the first phase of the study. RESULTS: After interruption of the basal insulin infusion during the insulin interruption phase, plasma insulin levels fell gradually in both groups to nadir values of 1.6 +/- 0.8 and 2.0 +/- 1.2 microU/ml in the regular insulin- and insulin lispro-treated groups, respectively. Plasma glucose concentrations rose to 13.8 +/- 1.9 and 16.0 +/- 1.7 mmol/l in the regular insulin- and insulin lispro-treated groups, respectively. No significant differences were seen between the therapy groups at any time in the insulin levels or in the concentrations of plasma glucose or beta-OHB. In the insulin replacement phase, insulin levels rose more rapidly in those treated with lispro insulin, reaching a greater peak value (e.g., at 60 min, plasma insulin 25 +/- 3.4 vs. 15.6 +/- 2.6 microU/ml, P < 0.05). In association with this, plasma glucose decreased to a lower nadir after lispro insulin (9.7 +/- 0.4 vs. 13.7 +/- 0.7 mmol/l, lispro- vs. regular-treated groups at 120 min after insulin administration, P < 0.01). beta-OHB levels decreased rapidly in both groups. CONCLUSIONS: In patients treated with CSII, interruption of the basal insulin infusion in the middle of the night does not result in more rapid metabolic decompensation in patients treated with lispro compared with those treated with regular human insulin. Lispro insulin is effective in treating mild ketosis and hyperglycemia, and its rapid action may be advantageous in the "sick day" management at home of patients with IDDM.

Acute Disease↗
PubMed1997

Progression of borderline increases in albuminuria in adolescents with insulin-dependent diabetes mellitus.

We aimed to determine the natural history of borderline increases in albuminuria in adolescents with insulin-dependent (Type 1) diabetes mellitus (IDDM) and factors which are associated with progression to persistent microalbuminura. Fifty-five normotensive adolescents with IDDM and intermittent microalbuminura (overnight albumin excretion ratte of 20-200 micrograms min-1 on one of three consecutive timed collections, n = 29) or borderline albuminura (mean overnight albumin excretion rate of 7.2-20 micrograms min-1 on one of three consecutive timed collections, n = 30) were followed prospectively at 3 monthly intervals. The endpoint was persistent microalbuminuria defined as a minimum of three of four consecutive overnight albumin excretion rates of greater than 20 micrograms min-1. One hundred and forty-two adolescents with IDDM and normoalbuminura were also followed prospectively. Fifteen of the 59 patients (25.4%) with intermittent (9/29) or borderline (6/30) albuminura progressed to persistent microalbuminura (progressors) over 28 (15-50) months [median (range)] in comparison with two of the 142 patients with normoalbuminuria at entry (relative risk = 12.6; p = 0.001). Progressors to persistent microalbuminura were pubertal and had higher systolic (p = 0.02) and diastolic (p = 0.02) blood pressure, and HbA1c (p = 0.004) than non-progressors. All patients remained normotensive. Glomerular filtration rate, apolipoproteins, dietary phosphorus, protein and sodium intakes, and prevalence of smoking did not differ between progressors and non-progressors. Total renin was higher in the diabetic patients without a difference between progressors and non-progressors. In conclusion there is a relatively high rate of progression to persistent microalbuminuria in pubertal adolescents with borderline increases in albuminura and duration greater than 3 years. These patients require attention to minimize associated factors of poor metabolic control and higher blood pressure in the development of incipient nephropathy.

Adolescent↗
PubMed1997

Incidence and predictive criteria of nocturnal hypoglycemia in young children with insulin-dependent diabetes mellitus.

OBJECTIVE: To determine the incidence of significant nocturnal hypoglycemia occurring at home in young children with insulin-dependent diabetes mellitus using conventional therapy. DESIGN: Sixty-one children (aged 2.6 to 8.5 years) were studied on one night, at home, with blood collection occurring at dinner, bedtime/supper, 11 PM, 2 AM, and breakfast, with subsequent laboratory analysis. RESULTS: The proportion of subjects with blood glucose levels less than 64, 55, 45, and 36 mg/dl (3.5, 3.0, 2.5, and 2.0 mmol/L) was 37.8%, 17%, 13%, and 8%, respectively. Nocturnal hypoglycemia was associated with younger age (< 5 years 57% vs 5 to 8.5 years 36%; p < 0.001) and lowered glycosylated hemoglobin levels (HbA1c) with a greater than 50% incidence of hypoglycemia seen in subjects with HbA1c levels of less than 8.5%. The average HbA1c concentration was lower in the hypoglycemic group than in the nonhypoglycemic group (7.8 vs 8.3%; p < 0.02). Nocturnal hypoglycemia occurred with increasing frequency throughout the night in subjects less than 5 years of age (dinner, supper, 11 PM, 2 AM, and breakfast incidences being 0%, 12.5%, 26%, 33%, and 30%, respectively) but not in those older than 5 years. Carbohydrate intake at supper did not prevent subsequent hypoglycemia. Blood glucose levels at 11 PM were poor predictors of subsequent hypoglycemia at 2 AM in either the group as a whole or in the children less than 5 years of age. Symptom recognition of nocturnal hypoglycemia was decreased in younger children (< 5 years (36%) > 5 years (58%)), in those with a lower HbA1c, and when hypoglycemia occurred at breakfast rather than at dinner (0% vs 50%). CONCLUSIONS: The incidence of nocturnal hypoglycemia in young children with insulin-dependent diabetes mellitus receiving conventional therapy is unacceptably high and is increased with lowered age and HbA1c concentration; the condition is often asymptomatic. Early-morning hypoglycemia is poorly predicted by a blood glucose determination at 11 PM and is not prevented by carbohydrate intake at supper. In younger children, blood glucose profiles should include early-morning measurements.

Age Factors↗
PubMed1997

Cytotoxicity and cell-proliferation induced by the nephrocarcinogen hydroquinone and its nephrotoxic metabolite 2,3,5-(tris-glutathion-S-yl)hydroquinone.

Hydroquinone, an intermediate used in the chemical industry and a metabolite of benzene, is a nephrocarcinogen in the 2-year National Toxicology Program bioassay in male Fischer 344 rats. Current evidence suggests that certain chemicals may induce carcinogenesis by a mechanism involving cytotoxicity, followed by sustained regenerative hyperplasia and ultimately tumor formation. Glutathione (GSH) conjugates of a variety of hydroquinones are potent nephrotoxicants, and we now report on the effect of hydroquinone and 2,3,5-(tris-glutathion-S-yl)hydroquinone, on site-selective cytotoxicity and cell proliferation in rat kidney. Male Fischer 344 rats (160-200 g) were treated with hydroquinone (1.8 mmol/kg or 4.5 mmol/kg, p.o.) or 2,3,5-(tris-glutathion-S-yl)hydroquinone (7.5 micromol/kg; 1.2-1.5 micromol/rat, i.v.), and blood urea nitrogen (BUN), urinary gamma-glutamyl transpeptidase (gamma-GT), alkaline phosphatase (ALP), glutathione-S-transferase (GST) and glucose were measured as indices of nephrotoxicity. Hydroquinone (1.8 mmol/kg, p.o.) is nephrotoxic in some rats, but not others, but cell proliferation (BrDU incorporation) in proximal tubular cells of the S3M region correlates with the degree of toxicity in individual rats. At 4.5 mmol/kg, hydroquinone causes significant increases in the urinary excretion of gamma-GT, ALP and GST. Pretreatment of rats with acivicin prevents hydroquinone-mediated nephrotoxicity, indicating that toxicity is dependent on the formation of metabolites that require processing by gamma-GT. Consistent with this view, 2,3,5-(tris-glutathion-S-yl)hydroquinone, a metabolite of hydroquinone, causes increases in BUN, urinary gamma-GT and ALP, all of which are maximal 12 h after administration of 2,3,5-(tris-glutathion-S-yl)hydroquinone. In contrast, the maximal excretion of GST and glucose occurs after 24 h. By 72 h, BUN and glucose concentrations return to control levels, while gamma-GT, ALP and GST remain slightly elevated. Examination of kidney slices by light microscopy revealed the presence of tubular necrosis in the S3M segment of the proximal tubule, extending into the medullary rays. Cell proliferation rates in this region were 2.4, 6.9, 15.3 and 14.3% after 12, 24, 48 and 72 h, respectively, compared to 0.8-2.4% in vehicle controls. Together with the metabolic data, the results indicate a role for hydroquinone-thioether metabolites in hydroquinone toxicity and carcinogenicity.

Animals↗
PubMed1997

Resistance to neuroglycopenia: an adaptive response during intensive insulin treatment of diabetes.

Counterregulation and awareness of hypoglycemia begins at lower plasma glucose levels in insulin-dependent diabetes mellitus (IDDM) subjects given intensive insulin treatment. To determine whether these changes are associated with an alteration in the susceptibility of the brain to mild hypoglycemia, we compared central nervous system responses to hypoglycemia in 8 intensively treated (hemoglobin A1, 8.3 +/- 0.2%; normal, <8%) and 11 conventionally treated IDDM patients (hemoglobin A1, 14.6 +/- 1.3%) with those in 10 healthy subjects. Plasma glucose was lowered from approximately 4.6 mmol/L in 0.5-0.6 steps using the clamp technique. Glucose levels triggering hormonal responses and perception of hypoglycemic symptoms were significantly lower in intensively treated patients compared to their poorly controlled counterparts (P < 0.05), and hormonal responses were suppressed compared to those in healthy controls. Similarly directed changes occurred in the level of circulating glucose required to alter cortical evoked potentials during hypoglycemia. A greater reduction in plasma glucose was required to alter P300 event-related potentials in the intensively treated patients (2.2 mmol/L) compared to those in the conventionally treated and nondiabetic groups (approximately 3.5 and approximately 3.0 mmol/L, respectively). We conclude that intensively treated IDDM patients are resistant to changes in cortical evoked potentials induced by mild hypoglycemia. This may explain why intensively treated IDDM counterregulate and experience hypoglycemic symptoms at a lower glucose level than conventionally treated patients.

Adaptation, Physiological↗
PubMed1997

Hypoglycemia: incidence and clinical predictors in a large population-based sample of children and adolescents with IDDM.

OBJECTIVE: To determine the frequency of moderate and severe hypoglycemia and to identify clinical predictors associated with its occurrence in a large population-based sample of children and adolescents with IDDM. RESEARCH DESIGN AND METHODS: A total of 657 patients (age: 12.1 +/- 4.4 years, mean +/- SD) were included in the study, yielding 1,449 patient-years of data. A prospective assessment of severe hypoglycemia (an event resulting in a seizure or coma) and moderate hypoglycemia (an event requiring assistance of another, excluding severe episodes) was made over a 3-year period. Patients and caregivers detailed episodes of significant hypoglycemia (moderate and severe events) and these were recorded at each 3-month clinic visit along with HbA1c. Data were analyzed using generalized estimating equation models fitted with the exchange correlation structure. RESULTS: The overall incidence of severe events was 4.8/100 patient-years and of moderate events was 13.1/100 patient-years. Over 3 years, severe events occurred in 8.5% of children and moderate events occurred in 26.9%. Significant hypoglycemia was rare in the first 12 months after diagnosis. Rates of hypoglycemia were increased in children < 6 years of age versus > 6 years of age (40.9 vs. 16.6/100 patient-years, age < or = 6 years vs. age > 6 years, P < 0.001). Rates of hypoglycemia doubled when HbA1c fell below 8%, and children with HbA1c < 7% had a threefold increase in both moderate and severe hypoglycemia (e.g., severe episodes 14.9 vs. 4.1/100 patient-years, HbA1c < or = 7% vs. HbA1c > 7%, P < 0.001). Most severe events were seizures, and 75% of them occurred at night. The majority of events were related to missed meals or increased activity. However, in 38% no predisposing factor was evident. CONCLUSIONS: Newly diagnosed children appear to be protected from severe hypoglycemia. Rates increase with lower glycated hemoglobin, especially when mean HbA1c is < 8.0%. Younger children, who may be more susceptible to the adverse effects of neuroglycopenia, are at a particular risk of significant hypoglycemia.

Adolescent↗
PubMed1997

The use of biothesiometry to detect neuropathy in children and adolescents with IDDM.

OBJECTIVE: To develop clinically useful reference ranges for vibration perception thresholds (VPTs), using biothesiometry in children and adolescents and to assess the reliability of the technique to identify subclinical neuropathy in subjects with IDDM at this age and to examine a large population-based sample of pediatric patients. RESEARCH DESIGN AND METHODS: VPTs were measured using a handheld biothesiometer at the medial malleolus and hallux in 232 nondiabetic children and adolescents aged 7-18 years (12.9 +/- 4.2 years) and a population-based sample of 307 young IDDM patients (13.3 +/- 4.6 years of age). The mean of three readings at each site was correlated with height, pubertal status, and age for all subjects and, in addition for the IDDM sample, with the duration of IDDM, ambient blood glucose, and mean HbA1c from diagnosis. Those IDDM subjects found to have elevated VPTs (> 97th percentile), and a control group of patients with IDDM underwent nerve conduction studies to determine the sensitivity and specificity of biothesiometry to detect abnormal neural function in children. Interoperator reliability was assessed in a separate trial in which two operators measured VPTs independently in the same 11 children. RESULTS: In the nondiabetic control subjects, height demonstrated the best correlation with VPT measures, and a reference range was thus established with percentile charts, using mean VPT and height. VPTs were higher in the diabetic sample, compared with the nondiabetic sample (P < 0.05). Of the children, 28 (9.1%) had VPT values > 97th percentile developed from studies of the nondiabetic subjects; of these, 11 were younger than 11 years and 8 were prepubertal. Nerve conduction studies confirmed reduced conduction velocity and prolonged distal latencies in those with abnormal VPTs, compared with normal control subjects and IDDM patients with normal VPTs. Sensitivity of biothesiometry to reflect abnormal nerve function was estimated as 82% and specificity as 75% at this age. Interoperator variation was small (7.25% of total variance). CONCLUSIONS: Biothesiometry is a useful noninvasive tool for the detection of subclinical neuropathy in children and adolescents. The use of height-related reference ranges may make screening for neuropathy more feasible in younger patients and allow large-scale longitudiral analysis of its development.

Adolescent↗
PubMed1996

Induction of a permeability transition in rat kidney mitochondria by pentachlorobutadienyl cysteine: a beta-lyase-independent process.

A Ca2+-dependent inner mitochondrial membrane permeability transition is induced by a number of agents, an effect which is thought to cause cytotoxicity. This transition involves formation of a pore allowing the passage of solutes of up to 1500 Da; it is blocked by cyclosporine A and Ca2+ chelating agents. The mitochondrial nephrotoxicant S-(1,2,3,4, 4-pentachlorobutadienyl)-L-cysteine (PCBC) caused collapse of the mitochondrial membrane potential, Ca2+-independent oxidation of pyridine nucleotides and release of accumulated Ca2+ in isolated rat kidney mitochondria, three hallmarks of the permeability transition. These effects were blocked by cyclosporine A and by ethylene glycol bis(beta-aminoethyl ether) tetraacetic acid (EGTA). Furthermore, EGTA was capable of reversing the collapse of the membrane potential. These data indicate that PCBC induced an inner membrane permeability transition. Interestingly, addition of aminoxyacetic acid, a beta-lyase inhibitor, did not prevent the permeability transition, and a nonmetabolizable analog of PCBC, S-(1,2,3,4, 4-pentachlorobutadienyl)-L-alpha-methyl cysteine, induced the permeability transition. Thus PCBC may act to induce the permeability transition through a mechanism that does not require metabolism by a beta-lyase. Since metabolism by a beta-lyase is required for PCBC toxicity, it is not clear that the permeability transition is involved in cysteine conjugate-mediated renal cell injury.

Acetylcysteine↗
PubMed1996

Glutathione conjugates of tert-butyl-hydroquinone, a metabolite of the urinary tract tumor promoter 3-tert-butyl-hydroxyanisole, are toxic to kidney and bladder.

3-tert-Butyl-4-hydroxyanisole and tert-butyl-hydroquinone (TBHQ) are antioxidants known to promote renal and bladder carcinogenesis in the rat, although the mechanisms of these effects are unclear. Because glutathione (GSH) conjugates of a variety of hydroquinones are nephrotoxic, and because 2-tert-butyl-5-(glutathion-S-yl)hydroquinone [5-(GSyl)TBHQ], 2-tert-butyl-6-(glutathion-S-yl)hydroquinone [6-(GSyl)TBHQ], and 2-tert-butyl-3,6-bis-(glutathion-S-yl)hydroquinone [3,6-bis-(GSyl)-TBHQ] have been identified recently as metabolites of TBHQ in the male rat, we investigated the effects of these metabolites in the male rat. At the highest dose tested (400 micromol/kg,i.v.) 5-(Gsyl)TBHQ and 6-(GSyl)TBHQ caused 2-fold increases in the urinary excretion of gamma-glutamyl transpeptidase and alkaline phosphatase, and pigments arising from the polymerization of metabolites were deposited in the kidney. 3,6-bis-(GSyl)TBHQ (200 micromol/kg) was the most potent of the GSH conjugates tested and produced significant increases in the urinary excretion of gamma-glutamyl transpeptidase, alkaline phosphatase, lactate dehydrogenase, and glucose (2-, 2-, 22-, and 11-fold increases, respectively). Alterations in the biochemical parameters correlated with the degree of single cell and tubular necrosis in the S(3)-M segment of the proximal tubule, as observed by light microscopy. In addition to nephrotoxicity, 3,6-bis-(GSyl)TBHQ increased the bladder wet weight 2-fold and caused severe hemorrhaging of the bladder. The half-wave oxidation potentials of 5-(Gsyl)TBHQ and 6-(GSyl)TBHQ were similar to that of TBHQ, whereas the half-wave oxidation potential of 3,6-bis-(Gsyl)TBHQ was approximately 100 mV higher than that of TBHQ. The TBHQ-GSH conjugates also catalyzed the formation of 8- hydroxydeoxyguanosine, indicating that GSH conjugation does not impair the redox activity of TBHQ. Because some chemicals may induce carcinogenesis by a mechanism involving cytotoxicity followed by sustained regenerative hyperplasia, our results suggest that the toxicity of GSH conjugates of TBHQ to kidney and bladder may contribute to the promoting effect of 3-tert-butyl-4-hydroxyanisole and TBHQ in these tissues.

Animals↗
PubMed1996

Trypanosomosis research at the Centre for Tropical Veterinary Medicine (CTVM) 1970 to 1995.

This review covers aspects of research work carried out on animal trypanosomes at the Centre for Tropical Veterinary Medicine (CTVM) during the last 25 years. The review covers work on antigenic variation, tissue culture, drug resistance, immunology, biochemistry and pathology of Trypanosoma brucei, T. congolense, T. gambiense and T. evansi. It is not intended as an exhaustive review of the subject but focuses on certain aspects of these areas which are presented in relation to work carried out within the broader scientific community.

Animals↗
PubMed1996

Nocturnal hypoglycaemia and sleep disturbances in young teenagers with insulin dependent diabetes mellitus.

OBJECTIVE: To determine the effect of nocturnal hypoglycaemia on sleep architecture in adolescents with insulin dependent diabetes mellitus (IDDM). DESIGN: 20 adolescents with IDDM (mean age 12.8 years, mean glycated haemoglobin (HbA1c) 8.9%) were studied on one night. Plasma glucose was measured every 30 minutes and cortisol and growth hormone levels every 60 minutes. Sleep was recorded using standard polysomnographic montages, and sleep architecture was analysed for total sleep time, stages 1-4, rapid eye movement, fragmentation, and arousals. RESULTS: Six subjects (30%) became hypoglycaemic (five subjects < 2.5 mmol/l), with one being symptomatic. There were no differences in age, HbA1c, duration of diabetes, or insulin regimen between hypoglycaemic and non-hypoglycaemic subjects. Hypoglycaemia was not predicted by glucose measurements before bed. There was no detectable rise in plasma cortisol or growth hormone concentrations during hypoglycaemia. Sleep architecture was not disturbed by nocturnal hypoglycaemia with no differences found in sleep stages, fragmentation, or arousals. CONCLUSIONS: Nocturnal hypoglycaemia is a common and usually asymptomatic complication of treatment in adolescents with IDDM. Moderate hypoglycaemia has not been shown to affect sleep architecture adversely. These findings are consistent with, and may explain, the observation that severe hypoglycaemia, with consequent seizure activity, is more common at night than during the day. Counterregulatory hormone responses to nocturnal hypoglycaemia may be less marked than with similar degrees of diurnal hypoglycaemia.

Adolescent↗
PubMed1996

General pharmacology of insulin lispro in animals.

[Lys(B28),Pro(B29)]-human insulin (insulin lispro, CAS 133107-64-9, LY275585, Humalog) is a quick acting insulin analog which is currently undergoing clinical evaluation for the treatment of diabetes. The potential secondary pharmacological activity of insulin lispro was profiled in studies for the evaluation of effects on the central and autonomic nervous system, the cardiovascular system, urine and electrolyte excretion, and gastrointestinal function. In vivo doses ranged from 0.03 to 10 U/kg, administered by the subcutaneous route, while pharmacologic activity in vitro was examined in smooth and cardiac muscle at concentrations of 1 x 10(-9) to 1 x 10(-5) mol/l. Insulin lispro exhibited secondary pharmacological activity in central nervous system tests only at higher doses with the most prominent observations being sedation and decreased responsiveness. Insulin lispro was essentially inactive in tests of autonomic (smooth and cardiac muscle), cardiovascular (mean arterial pressure, heart rate, systolic pressure, diastolic pressure, and pulse pressure), renal (urine and electrolyte excretion) and gastrointestinal (motility) function. In summary, insulin lispro had minimal effect in these pharmacodynamic studies indicating that insulin lispro has minimal potential to produce adverse pharmacological side effects at clinically relevant doses.

Animals↗
PubMed1995

Enhanced adrenomedullary response and increased susceptibility to neuroglycopenia: mechanisms underlying the adverse effects of sugar ingestion in healthy children.

OBJECTIVE: Eating simple sugars has been suggested as having adverse behavioral and cognitive effects in children, but a physiologic mechanism has not been established. This study was performed to address this issue. DESIGN: Metabolic, hormonal, and symptomatic responses to a standard oral glucose load (1.75 gm/kg; maximum, 120 gm) were compared in 25 healthy children and 23 young adults, and the hypoglycemic clamp, together with measurements of P300 auditory evoked potentials, was used to assess whether children are more vulnerable than adults to neuroglycopenia. SETTING: Children's Clinical Research Center, Yale University School of Medicine. RESULTS: Baseline and oral glucose-stimulated plasma glucose and insulin levels were similar in both groups, including the nadir glucose level 3 to 5 hours after oral administration of glucose (3.4 +/- 0.1 mmol/L (61 +/- 1.8 mg/dl) in children and 3.5 +/- 0.1 mmol/L (63 +/- 1.8 mg/dl) in adults). The late glucose decrease stimulated a rise in plasma epinephrine levels that was twofold higher in children than in adults (2260 +/- 289 vs 1031 +/- 147 pmol/L (407 +/- 52 vs 186 +/- 26 pg/ml), p < 0.01) and a significant increase in hypoglycemic symptom scores in children (p < 0.01), but not in adults. During control experiments, in which six of the healthy children ingested a sugar-free drink, there were no significant changes in plasma glucose levels, hormone concentrations, or hypoglycemic symptom scores. During the hypoglycemic clamp, P300 potentials did not change in any of eight adult subjects until the plasma glucose concentration was lowered to 3.0 mmol/L (54 mg/dl), whereas similar changes in P300 potentials were observed in six of seven children at glucose levels 3.6 to 4.2 mmol/L (65 to 75 mg/dl). CONCLUSION: Enhanced adrenomedullary responses to modest reductions in plasma glucose concentration and increased susceptibility to neuroglycopenia may be important contributing factors to adverse behavioral and cognitive effects after sugar ingestion in healthy children.

Adolescent↗
PubMed1995

Growth and growth hormone secretion after treatment for acute lymphoblastic leukemia in childhood. 18-Gy versus 24-Gy cranial irradiation.

PURPOSE: Cranial irradiation (CI) given during the first phase of treatment of childhood acute lymphoblastic leukemia (ALL) has been associated with significant long-term morbidity. As a result, the dose of radiotherapy has been reduced from 24 to 18 Gy to reduce the severity of these late effects. To compare the effects of 24 and 18 Gy CI on growth, puberty, and growth hormone (GH) secretion, a cohort of survivors of childhood ALL were studied. PATIENTS AND METHODS: Of a total of 48 children, 28 (14 boys, 14 girls) had received 24 Gy and 20 (eight boys, 12 girls) had received 18 Gy. Similar chemotherapy regimens had been used in both groups, and age at diagnosis (5.2 +/- 2.7 vs. 5.1 +/- 2.8 years, 18 Gy vs. 24 Gy) and mean height at diagnosis [standard deviation score (SDS) 0.17 +/- 0.17 vs. 0.05 +/- 0.17, 18 Gy vs. 24 Gy] were comparable. RESULTS: Growth rates in both groups did not differ for the first 5 years after diagnosis. After this time, however, a significant height decrease was observed in children who had received 24 Gy but not in children who had received 18 Gy (at 8 years the change in SDS from diagnosis was -0.32 +/- 0.14 vs. -0.73 +/- 0.16, 18 Gy vs. 24 Gy, p < 0.05). Menarche occurred earlier in the girls in the 24-Gy group (at 12.9 +/- 0.3 vs. 11.7 +/- 0.4 years of age, 18 Gy vs. 24 Gy, p < 0.02). Overnight GH concentrations (12-h sampling every 20 min) were reduced in both groups compared with healthy age-matched control children but were even lower in the 24-Gy group (12.7 +/- 0.7 mU/L vs. 7.9 +/- 0.6 vs. 6.1 +/- 0.5 [6.4 +/- 0.4 ng/ml vs. 3.9-0.3 vs. 3.1 +/- 0.3]; control vs. 18 Gy and 24 Gy, p < 0.001; 18 Gy vs. 24 Gy, p < 0.025). CONCLUSIONS: Although both doses of CI impair GH secretion, 24 Gy has a greater impact on growth in the long term. This effect may be exaggerated by the induction of early puberty in some children.

Age Factors↗
PubMed1995

Blunted catecholamine responses after glucose ingestion in children with attention deficit disorder.

Eating simple sugars has been suggested as having adverse behavioral and cognitive effects in children with attention deficit disorder (ADD), but a physiologic mechanism has not been established. To address this issue, metabolic, hormonal, and cognitive responses to a standard oral glucose load (1.75 g/kg) were compared in 17 children with ADD and 11 control children. Baseline and oral glucose-stimulated plasma glucose and insulin levels were similar in both groups, including the nadir glucose level 3-5 h after oral glucose (3.5 +/- 0.2 mmol/L in ADD and 3.3 +/- 0.2 mmol/L in control children). The late glucose fall stimulated a rise in plasma epinephrine that was nearly 50% lower in ADD than in control children (1212 +/- 202 pmol/L versus 2228 +/- 436 pmol/L, p < 0.02). Plasma norepinephrine levels were also lower in ADD than in control children, whereas growth hormone and glucagon concentrations did not differ between the groups. Matching test scores were lower and reaction times faster in ADD than in control children before and after oral glucose, and both groups showed a deterioration on the continuous performance test in association with the late fall in glucose and rise in epinephrine. These data suggest that children with ADD have a general impairment of sympathetic activation involving adrenomedullary as well as well as central catecholamine regulation.

Adolescent↗
PubMed1994

Dramatic increase in incidence of insulin dependent diabetes mellitus in Western Australia.

OBJECTIVES: To document and suggest possible reasons for a dramatic increase in the incidence of insulin dependent diabetes mellitus (IDDM) in Western Australia in 1992. PATIENTS: Children aged 0-14 years with IDDM diagnosed in Western Australia from 1985 to 1992 inclusive. DESIGN: A population-based register in Western Australia, using name-identified data from two separate ascertainment sources, provided numerator data. Denominator data were estimated from census figures collected in 1986 and 1991 by the Australian Bureau of Statistics. The completeness of case ascertainment was estimated by the capture-recapture method. RESULTS: Case ascertainment for 1985-1992 was estimated as 99.6% complete. Between 1985 and 1991 the incidence of IDDM in the 0-14 year age group varied between 11.8 and 15.5 per 100,000 person-years without a significant increase. In 1992, however, based on the previous seven years, 52 cases would have been expected but 84 cases were observed, an incidence of 22.2 per 100,000 person-years. The increase in incidence occurred across all age groups and in both sexes. Place of residence at diagnosis, the prevalence of islet cell antibody positivity at diagnosis and the proportion of new cases with a first degree relative with IDDM were no different in 1992 than in preceding years. CONCLUSION: This is the first report of a significant increase in the incidence of IDDM in Australia. It appears to be a period, rather than a cohort, effect and provides further evidence for environmental antigens as disease triggers.

Adolescent↗