Permanent neonatal diabetes mellitus and pancreatic exocrine insufficiency resulting from congenital pancreatic agenesis.
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Blood Glucose↗
Biomedical subjects
N M Wright
Publications and source records attributed to N M Wright.
Spontaneous growth hormone release in term infants: changes during the first four days of life.
Healthy term infants have higher umbilical cord GH levels compared to older infants and children. In the sheep, GH concentrations rapidly fall within an hour of birth; the physiology of GH release after parturition in the human term infant is less well known. The purpose of this study was to investigate spontaneous 12-h GH release in male and female term infants of varying postnatal ages. We studied 14 infants (7 males and 7 females). Subjects were divided into those studied earlier following delivery (28.2 +/- 3.4 h of age, mean +/- SE) and into those studied at a later time (74.8 +/- 3.5 h, P < 0.0005). The age at study was defined as the age (hours) when blood sampling began. There were eight infants studied at an early age (four males and four females) and six studied at a later age (three males and three females). Subjects were comparable with respect to gestational age, birth weight, and length; all were biochemically euthyroid. One infant was large for gestational age although his head circumference was in the normal range. Blood (0.1 mL) was taken every 30 min over a 12-h period from an indwelling umbilical catheter; no stress occurred during the blood withdrawal. GH was determined by a double-antibody RIA using 0.01 mL plasma. GH pulse detection was undertaken using Cluster, a computerized pulse detection algorithm. Total insulin-like growth factor I (IGF-I) was measured following separation of the IGFs from the serum binding proteins. Spontaneous pulsatile GH release was observed in all infants studied. No differences in GH characteristics were found between male and female subgroups in the early or late study groups. In subsequent analysis, the data for the males and females are combined. The GH pulse frequency per 12 h was greater in the earlier studied group, 5.1 +/- 0.9 (mean +/- SE) vs. 2.5 +/- 0.7 in the later group (P < 0.05). The maximal pulse amplitude was 47.1 +/- 7.9 micrograms/L in the early and 27.1 +/- 4.1 in the later studied group (P < 0.06). The incremental pulse amplitude was 26.4 +/- 3.4 micrograms/L in the early and 12.8 +/- 2.7 in the later group (P = 0.01). The pulse width was greater in the later studied group (202.8 +/- 71.1 min vs. 84.1 +/- 21.6, P < 0.06).(ABSTRACT TRUNCATED AT 400 WORDS)
Aging↗
Characterization of pulsatile secretion and clearance of plasma cortisol in premature and term neonates using deconvolution analysis.
Pulsatile secretion of cortisol (F) has not been documented in the newborn infant. Using repeated blood sampling and deconvolution analysis, we investigated F secretion and elimination dynamics in a group of five premature (gestational age, 24-34 weeks) and five term neonates. These infants had required placement of an umbilical arterial cannula for monitoring respiratory status, but were otherwise clinically stable. Blood samples were obtained at 15-min intervals for a 6-h period. All plasma F determinations were 58 nmol/L (2.1 micrograms/dL) or more, and pulsatile F secretion was observed in all infants. No significant differences were noted between the two groups with regard to 6-h mean plasma F concentration [350 +/- 129 (premature) vs. 277 +/- 54 nmol/L (term)], plasma corticosteroid-binding globulin (14 +/- 0 vs. 13 +/- 1 mg/L), F secretory burst frequency (4 +/- 0 vs. 5 +/- 1 bursts/6 h), mass of F secreted per burst [760 +/- 480 vs. 310 +/- 100 nmol/Lv [Lv, liter of F distribution volume)], F production rate (FPR; 2.7 +/- 1.4 vs. 1.1 +/- 0.2 mumol/Lv.6 h), or plasma F half-life (45 +/- 6 vs. 56 +/- 4 min). However, the premature infants had a significantly longer F secretory burst half-duration (63 +/- 18 vs. 6.7 +/- 4.0 min; P < 0.01) and a significantly lower maximal F secretory rate (9.4 +/- 3.4 vs. 100 +/- 26 nmol/Lv.min; P < 0.02) than the term infants. Body surface area and body weight were inversely correlated with F secretory burst half-duration (r = -0.74 and -0.75, respectively); both were also positively correlated with the maximal F secretory rate (r = 0.66 and 0.72). The two most premature infants had significantly greater mean plasma F and FPR than the other three premature and all of the term infants. Extrapolating to 24 h and correcting for the distribution volume of F and body surface area, we estimate FPR to be approximately 17-24 mumol/m2.24 h (6.6-8.8 mg/m2.24 h) for newborn infants of 34 weeks or more gestational age. These values are consistent with newer estimates of FPR in older children and adults determined using either deconvolution analysis or stable isotope dilution methods.
Adrenal Cortex↗
Elevated growth hormone secretory rate in premature infants: deconvolution analysis of pulsatile growth hormone secretion in the neonate.
Premature infants have higher circulating concentrations of growth hormone (GH) than term infants. Previous investigations of these differences have used sampling frequencies of every 30 min with subsequent application of pulse detection algorithms, such as the CLUSTER program, to assess serum GH pulse parameters. To determine differences in GH secretory rates or GH t1/2 values between premature and term infants, we have sampled 11 neonates at 15-min intervals. We performed deconvolution analysis of the resultant plasma GH values to estimate GH secretory and clearance parameters. Five premature infants (gestational age range 24-34 wk) and six term infants (gestational age range 38-42 wk) were sampled every 15 min for 6 h. All subjects had indwelling arterial catheters. GH was measured (in duplicate) by RIA using 10 microL of plasma. Premature infants had higher secretory burst amplitudes (2.2 +/- 0.13 micrograms/L/min versus 1.4 +/- 0.27 micrograms/L/min, p = 0.02), higher production rates (product of the total number of bursts and the mean mass of GH secreted per burst, 811 +/- 173 micrograms/L/6 h versus 283 +/- 77 micrograms/L/6 h, p = 0.03), and a higher mass of GH per secretory burst (106 +/- 25 micrograms/L versus 38 +/- 11 micrograms/L, p = 0.049) than term infants. The integrated plasma GH concentration exhibited a strong trend toward a higher value in the premature infants (18,100 +/- 800 micrograms/L versus 10,200 +/- 2,700 micrograms/L, p = 0.067).(ABSTRACT TRUNCATED AT 250 WORDS)
Female↗
Spontaneous and stimulated growth hormone release in adolescents with type I diabetes mellitus: effects of metabolic control.
Abnormalities in GH release have been found in adults with poorly controlled type I diabetes mellitus. During puberty, circulating GH concentrations transiently increase. To investigate in pubertal diabetic adolescents, the physiological relationship between metabolic control and GH release, we compared spontaneous and GH-releasing hormone (GHRH)-stimulated GH release in six pubertal subjects during poor (study A) and improved (study B) metabolic control. The subjects included two females and four males (mean age +/- SE, 15.5 +/- 1 yr; duration of diabetes, 8.6 +/- 0.9 yr; Tanner stages II-V). Serum samples for glucose and GH determinations were obtained at 20-min intervals over a 24-h period. Significant pulses of GH release were identified using a pulse detection algorithm (Cluster). Fourier expansion time series was used to document the occurrence of significant periodicities in the GH concentration-time data series. All subjects received 1.0 microgram/kg GHRH-44, iv, at 0800 h on the day after the 24-h monitoring for GH. After GHRH administration, samples were taken for glucose and GH determinations over 90 min. The overall mean glucose level (+/- SE) during the 24-h monitoring was 11.5 +/- 0.2 mmol/L during study A and 7.2 +/- 0.2 during study B (P = 0.0001). During the 4 weeks of improved control, glycated hemoglobin fell from 13.9 +/- 1.4% to 11.7 +/- 0.8% (mean +/- SE; P < 0.025). All subjects had significant pulses of GH release during poor or improved metabolic control. Relative to that at night, the daytime pulse frequency was higher in study A (P < 0.025). The overnight pulse frequency increased during study B (P < 0.01). Other pulse parameters, including maximal and incremental pulse amplitudes, pulse width, and interpulse valley mean, did not change during improved control. The mean +/- SE 24-h GH concentration was 4.1 +/- 0.7 micrograms/L during study A and 4.3 +/- 0.8 during study B. The amplitude of the circadian GH rhythm was not different by Fourier analysis. The overall mean glucose +/- SE after GHRH administration was 15.3 +/- 0.2 mmol/L in study A and 6.8 +/- 0.1 in study B. In spite of the marked hyperglycemia during study A, the GH responses were similar during studies A and B. Maximal GH levels were obtained at 15-30 min (mean +/- SE) and were 36.0 +/- 16.9 micrograms/L in study A and 38.7 +/- 18.9 in study B.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Spontaneous pulsatile growth hormone release in male and female premature infants.
Although premature infants have high umbilical cord GH levels, little is known about spontaneous GH release in these individuals. The purpose of our study was to investigate spontaneous 12-h GH release in appropriate for gestational age male and female premature infants. We studied 22 premature infants (15 males and 7 females) of appropriate length and weight for age. Gestational ages, birth weights, birth lengths, and ages at the time of study were similar in male or female infants. All infants were biochemically euthyroid. Blood was taken every 30 min over a 12-h period from an indwelling umbilical catheter; no stress occurred during the blood withdrawal. GH was determined by a double antibody RIA, using 0.01 mL plasma. GH pulse detection was undertaken using Cluster, a computerized pulse detection algorithm. Total insulin-like growth factor-I and -II (IGF-I and -II) levels were measured after separation of the IGFs from the serum binding proteins. Spontaneous pulsatile GH release was observed in all infants studied. No differences were found between males and females in the pulse characteristics of frequency, maximal amplitude, incremental amplitude, width, or area. The GH pulse frequency per 12 h was 3.2 +/- 0.3 (mean +/- SE) in males and 3.0 +/- 0.7 in females. The maximal pulse amplitude was 50.7 +/- 6.2 micrograms/L in males and 44.7 +/- 9.0 micrograms/L in females. The incremental pulse amplitude was 24.3 +/- 3.2 micrograms/L in males and 20.2 +/- 3.9 micrograms/L in females. The mean 12-h GH level was 37.1 +/- 4.8 micrograms/L in males and 35.8 +/- 8.5 micrograms/L in females; the average GH nadir was 26.1 +/- 4.0 micrograms/L in males and 24.4 +/- 8.3 micrograms/L in females. Both IGF-I and IGF-II concentrations were similar in males and females. The mean IGF-I levels were 10.7 +/- 1.5 ng/mL in males and 7.5 +/- 1.1 ng/mL in females; IGF-II levels were 96.0 +/- 12.0 ng/mL in males and 115.4 +/- 17.1 ng/mL in females. These results demonstrate similar pulsatile GH release in male and female premature infants at a mean age of 32-33 weeks. Compared with previously reported values for mean GH concentration and average GH nadir in older children, the values in these premature infants were much higher. We speculate that the higher GH levels in premature infants may result from decreased negative feedback associated with low IGF-I levels. The premature infant's somatotrophs may also not fully respond to the GH inhibitory action of somatostatin.
Blood Glucose↗
Prospective evaluation of a watch policy in patients with inoperable non-small cell lung cancer.
The requirement for palliative chest radiotherapy in patients with non-small cell lung cancer (NSCLC) was assessed in a study of 134 inoperable patients not suitable for radical radiotherapy. Immediate chest radiotherapy was judged necessary in 86 (64%) because of significant symptoms from intrathoracic tumour or involvement of proximal airways. Forty-eight patients were monitored regularly without initial radiotherapy and of these, 26 (54%) required later chest irradiation because of progressive and significant symptoms due to intrathoracic disease. Median symptom-free survival in this group was 10 months. The requirement for immediate or delayed chest irradiation could not be predicted from either patient or tumour characteristics. The proportion of patients with NSCLC requiring palliative chest irradiation may have been overestimated from this study population; even so 22 of 134 patients (16%) did not at any stage in their illness require radiotherapy for chest symptoms.
Adult↗
Estrogen and diclofenac sodium therapy in a prepubertal female with idiopathic juvenile osteoporosis.
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Calcitriol↗