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Biomedical subjects

J Litton

Publications and source records attributed to J Litton.

12 recordsLinked to original sources

Dual hormonal replacement therapy with insulin and recombinant human insulin-like growth factor (IGF)-I in insulin-dependent diabetes mellitus: effects on the growth hormone/IGF/IGF-binding protein system.

Patients with insulin-dependent diabetes mellitus (IDDM) exhibit abnormalities in the GH/insulin-like growth factor (IGF) axis, including GH hypersecretion, low serum IGF-I and IGF-binding protein-3 (IGFBP-3) levels, and elevated IGFBP-1 levels. We recently demonstrated that in IDDM, dual hormonal replacement therapy with insulin plus recombinant human IGF-I (rhIGF-I) improves glycemic control better than insulin alone. To determine whether the addition of rhIGF-I therapy to insulin therapy also corrects GH/IGF/ IGFBP abnormalities, we examined the effects of chronic combined rhIGF-I/insulin therapy on key components of the somatotropin axis. Forty-three pediatric IDDM patients were randomly assigned to groups receiving daily, fasting subcutaneous injections of placebo or rhIGF-I (80 micrograms.kg.day) for 28 days, while continuing to receive splitmix insulin therapy and intensive outpatient management. rhIGF-I therapy corrected IGF-I deficiency, suppressed IGFBP-1 levels (P < 0.01), and induced a trend toward lower circulating GH levels throughout the study. rhIGF-I therapy also induced an approximate 50% decrease in IGF-II levels (P < 0.001) and an approximate 70% increase in IGFBP-2 levels (P < 0.05). Serum IGFBP-3 levels, normal before treatment, remained normal during rhIGF-I administration. All effects were apparent during the first week of rhIGF-I therapy and persisted throughout treatment. Because improvements in the GH/ IGF axis abnormalities and in glycemic control were greater in subjects receiving combined rhIGF-I and insulin, these data strongly support the concept that dual hormonal replacement in IDDM may offer distinct therapeutic advantages over insulin monotherapy.

Adolescent↗

Dual hormonal replacement with insulin and recombinant human insulin-like growth factor I in IDDM. Effects on glycemic control, IGF-I levels, and safety profile.

OBJECTIVE: To examine if dual replacement with insulin and rhIGF-I, recombinant human insulin-like growth factor I (rhIGF-I) may be safe and result in improved metabolic control and reduced insulin usage. RESEARCH DESIGN AND METHODS: Forty-three patients with IDDM were randomized to receive a daily injection of rhIGF-I (80 mcg/kg s.c.) or placebo while on conventional insulin therapy for 4 weeks. Insulin was adjusted in the attempt to achieve predetermined goal glycemic values. Free and total IGF-I, four daily blood glucoses, and HbA1c were measured. RESULTS: Before randomization, placebo and rhIGF-I groups exhibited low plasma levels of free and total IGF-I, which increased toward normal levels during the treatment period only in the rhIGF group. The regression curve obtained from the average of daily blood glucose measurements indicated that the glycemic profile, overlapping in the lead-in period, exhibited a downward trend in the rhIGF-I group during the treatment period. Mean blood glucose level during the last 10 days of treatment was lower in the rhIGF-I groups (174 +/- 37 vs. 194 +/- 32 mg/dl). HbA1c level was reduced by more than one-half percent more in the rhIGF-I group (-1.85%) than in the control group (-1.3%). The dose of regular insulin was significantly lower in the rhIGF-I group (0.2 +/- 0.1 vs. 0.28 +/- 0.1 U. kg-1. 10 days-1 in the placebo group; P < 0.05). CONCLUSIONS: rhIGF-I in combination with conventional insulin treatment ameliorated the low plasma total and free IGF-I levels and was well tolerated in IDDM. There was a trend toward improved glycemic control, while the regular insulin dose was significantly decreased.

Adolescent↗

Glycosylated hemoglobin: a sensitive indicator of gestational diabetes.

Previous studies suggested that the assessment of hemoglobin A1 (HbA1) concentration was a poor indicator of diabetes in pregnancy. However, HbA1 was measured by ion exchange chromatography, which is subject to spurious alterations. To reevaluate the use of glycosylated hemoglobin concentration (GlyHb) as an indicator of gestational diabetes, 64 women at 10 to 15 weeks' gestation were studied by measuring GlyHb by a specific affinity chromatography assay, and blood glucose concentration was determined one hour post a 50-g oral glucose load. Gestational diabetes developed in 15 women in whom GlyHb (7.4 +/- 0.2%) was greater than in normal pregnant women (5.7 +/- 0.1%, P less than .001). If a GlyHb of 6.3% were chosen as the threshold for diagnostic evaluation for diabetes, only 6.7% of the gestational diabetics would have missed diagnosis. Of normal women, 14.2% would have been subjected to glucose tolerance test. GlyHb elevation was associated with the birth of infants large for gestational age. The assessment of GlyHb by affinity chromatography between 10 and 15 weeks' gestation may be a sensitive predictor of patients who will develop gestational diabetes.

Adolescent↗

The correlations of glycosylated serum protein and glycosylated hemoglobin concentrations with blood glucose in diabetic pregnancy.

The usefulness of concentrations of glycosylated serum protein and glycosylated hemoglobin in monitoring glycemic control during pregnancy complicated by diabetes was evaluated by correlation of these parameters with fasting and 2-hour postprandial glucose concentrations of the previous 7 days. Glycosylated serum protein correlated with both fasting (r = 0.798, p less than 0.01, n = 71) and postprandial (r = 0.846, p less than 0.01, n = 69) blood glucose concentrations. Glycosylated hemoglobin also correlated with fasting (r = 0.571, p less than 0.01, n = 71) and postprandial (r = 0.510, p less than 0.01, n = 74) blood glucose concentrations. Monitoring glycosylated serum protein during pregnancy complicated by diabetes is clinically feasible and allows frequent reappraisal of diabetic control.

Adult↗

Performance study of the PC-384 positron camera system for emission tomography of the brain.

A positron camera system PC-384 has been designed and built for quantitative positron emission computed tomography of the brain. This head scanner consists of 384 bismuth germanate oxide scintillation detectors with a crystal packing fraction of 80%. The entire detector assembly rotates around a small circle (wobble) to achieve the necessary ray sampling. Seven simultaneous images are produced with four detector rings. Performances of the system are discussed and clarified based on experimental data.

Brain↗

Correction for scattered radiation in a ring detector positron camera by integral transformation of the projections.

A "deconvolution" algorithm for the determination of the scatter contribution in positron emission tomography is described. The projected distributions of scattered radiation measured with a line source at different positions in water phantoms are described analytically. It is shown that an integral transformation of the observed projections with a slightly modified analytical function gives an adequate description of the scattered radiation. The scatter distribution from any composite object can thus be calculated and subsequently subtracted. The algorithm is tested on different objects. The result shows that the level of scattered radiation can be reduced from 25 to 1% of the total count rate in the center of the projection from a homogeneous phantom.

Models, Theoretical↗

Determination of object contour from projections for attenuation correction in cranial positron emission tomography.

A contour-finding algorithm is described by which the object periphery is outlined in positron emission tomography (PET) scans. The positions of maximum slopes are determined in the projections. These positions are shown to correspond well to the borders of the activity region. By backprojecting these points in the projections into the image plane, the size and shape of the region of activity must be outlined. Cord lengths across this region are then determined for attenuation correction. The accuracy of the algorithm has been tested on 10 patients with both PET and computed tomography (CT) examinations. Points on the periphery of the skull, as determined with the contour-finding algorithm in PET, coincided with those determined by CT, with a standard deviation of 1.5 mm and a maximum deviation of 3.5 mm. In testing the influence of the skull bone on the PET values, it was found that ignoring the higher attenuation coefficient of bone, 5 mm thick, in the attenuation correction caused an error in the determination of activity of 11% peripherally and 6% centrally in the object. These errors could be reduced to less than 1% by increasing the assumed attenuating region by 4.5 mm.

Brain↗

A ring detector positron camera system: its merits: clinical experience.

A ring detector positron camera system for CT of the brain is described. The system uses 95 NaI (Tl) detectors, arranged with cylindrical geometry, for the simultaneous detection of coincidences from 1,900 detector combinations. With a new sampling technique an experimental system resolution of 7 mm FWHM has been obtained. The sensitivity was found to be 5,300 c/s with a 100-keV energy threshold and using a 19.2-cm-diameter cylindrical phantom with a homogeneous specific activity of 1 muCi/cm3. A clinical study of blood-brain barrier damage using 68Ga-EDTA is reported.

Brain↗

Type A behavior pattern and blood glucose control in diabetic children.

We studied the relationship between presence of Type A behavior pattern and glycemic response to stress in children with insulin dependent diabetes mellitus (IDDM). Twelve male (six Type A and six Type B) and nine female (four Type A and five Type B) insulin-dependent diabetic patients between the ages of 8 and 16 years received a standard meal and blood glucose values were assessed two hours later. All subjects then played a competitive videogame for 10 minutes following which blood glucose was assessed again. Preprandial and postprandial blood glucose values did not differ between the groups. However, only Type A subjects showed a hyperglycemic response to the videogame stress. Type A subjects also demonstrated significantly higher glycohemoglobin values. In order to assure that this effect was due to a differential response to stress and not simply a difference in metabolic response to a meal, a second study was conducted in which blood glucose values were assessed at one, two and three hours following a standard meal. No significant differences in postprandial blood glucose values were observed between Type A and Type B subjects. These data support previous research which has suggested that some but not all patients with IDDM show a hyperglycemic response to stress.

Adolescent↗