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Biomedical subjects

T A Buchanan

Publications and source records attributed to T A Buchanan.

87 records · Page 5Linked to original sources
PubMed1986

Embryotoxic effects of brief maternal insulin-hypoglycemia during organogenesis in the rat.

To test whether maternal hypoglycemia can impair organogenesis, we induced brief glucopenia with insulin in conscious pregnant rats during either the headfold stage or the early neural tube closure stage of embryogenesis. At each time, 10 pairs of animals received identical insulin infusions for 1 h. Half the animals were maintained at euglycemia during the infusions, while the others were allowed to become hypoglycemic. Euglycemia was maintained or restored in all animals immediately after the insulin was stopped. Spontaneous activity was diminished during the hypoglycemia but consciousness was preserved. Embryos were removed from mothers and examined 2 d later. This examination revealed that embryos from the hypoglycemic mothers were growth-retarded and displayed a small but significant incidence of gross developmental anomalies compared with embryos from the insulin-infused euglycemic mothers. Thus, brief, mild maternal hypoglycemia during early organogenesis can disrupt normal embryo development in the rat. The effect is due to the hypoglycemia per se rather than to the insulin employed for its induction.

Animals↗
PubMed1986

The metabolic clearance, distribution, and degradation of dimeric and monomeric growth hormone (GH): implications for the pattern of circulating GH forms.

The ratio of oligomeric (big) to monomeric (little) human (h)GH forms in plasma exceeds that in the pituitary gland severalfold. To investigate whether delayed metabolic clearance of oligomers could explain this discrepancy, we measured MCR, distribution volumes, and degradation rates of radio-labeled hGH22K dimer, hGH20K dimer, hGH22K monomer, and hGH20K monomer in the rat. Hormones were injected as a bolus, and disappearance from plasma was followed by immunoprecipitation and trichloroacetic acid precipitation. MCRs of the dimers were significantly lower than those of the corresponding monomers (5-fold in the case of hGH22K, and 2-fold in the case of hGH20K). Both dimers were also degraded at slower rates than the monomers. Distribution volumes for the dimers, although somewhat smaller, were not statistically different from those for the monomers and were consistent with distribution in the extracellular space. We conclude that hGH dimers are relatively protected from degradation and hence cleared more slowly from the blood than hGH monomers. This may lead to their accumulation in the circulation relative to their monomeric counterparts, which may explain their high proportion in plasma as compared to pituitary.

Animals↗
PubMed1985

Slow metabolic clearance rate of the 20,000-dalton variant of human growth hormone: implications for biological activity.

The 20,000-dalton variant of human GH (hGH) (20 K) exhibits full growth-promoting bioactivity in the rat despite its poor interaction with GH receptors, as compared to the principal 22,000-dalton form of hGH (22 K). To test the possibility that prolonged survival time of 20 K in vivo may contribute to this apparent discrepancy, we compared the MCRs of 22 K and 20 K in the rat by the single injection technique. Both radiolabeled and native 22 K and 20 K were examined in this regard. The MCR of 20 K was 2- to 3-fold lower than that of 22 K, a statistically significant difference (P less than 0.05). The distribution volumes were similar for the two hGH forms and corresponded approximately to the extracellular fluid space. We conclude that the prolonged persistence of 20 K in the circulation may contribute to its higher than expected bioactivity in vivo in the rat.

Animals↗
PubMed1985

The medical management of diabetes in pregnancy.

This article is divided into three sections. "Metabolic Adaptations to Normal Pregnancy" describes the changes in intermediary metabolism that normally attend pregnancy and relates these changes to states of insulin deficiency--i.e., diabetes. "Implications for the Conceptus" reviews our current understanding of how the metabolic derrangements that characterize maternal diabetes may affect embryo and fetal development. "Management" details practical aspects of a management program aimed at normalizing pregnancy outcome for women with both pregestational and gestational diabetes mellitus.

Blood Glucose↗
PubMed1984

An ultrastructural study of retinal photoreceptor degeneration associated with bronchial carcinoma.

We studied both eyes of a 66-year-old man with retinal degeneration and oat cell carcinoma of the bronchus. Retinal degeneration was most marked peripheral to the parafovea where photoreceptor cells and their outer segments were absent. Within the parafovea, photoreceptor cells remained but rod outer segments were absent and cone outer segments were fragmented and disorganized. The retinal pigment epithelium contained many immature melanin granules within melanolysosomes, suggesting abnormal melanin synthesis and resorption. We suggest that a pharmacologically active substance resembling a hormone produced by the tumor increased melanin synthesis in the pigment epithelium and that the increased melanin content in these cells compromised their ability to phagocytose and maintain normal turnover of photoreceptor outer segments. We believe these changes led to photoreceptor outer segment loss and subsequent degeneration of the photoreceptor cells.

Aged↗
PubMed1983

Fatal fat embolism after spinal fusion for scoliosis.

An adolescent girl who underwent Harrington instrumentation and spinal fusion for idiopathic scoliosis had the adult respiratory distress syndrome develop in the immediate postoperative period. Massive fat embolization to the lungs was present at postmortem examination, an apparently rare complication of this surgical procedure. This case emphasizes the necessity of maintaining a high index of suspicion. In any clinical setting that would place a patient at risk for fat emboli and illustrates the unreliability of many of the clinical and laboratory features frequently described as useful for establishing the diagnosis.

Adolescent↗
PubMed1982

Bilateral proptosis, dilatation of conjunctival veins, and papilloedema: a neuro-ophthalmological syndrome caused by arteriovenous malformation of the torcular herophili.

A patient with an occipital dural arteriovenous malformation (AVM) developed signs of a carotid-cavernous sinus fistula and raised intracranial pressure. Bilateral transverse sinus occlusion associated with the AVM produced these signs by rerouting intracranial venous drainage anteriorly through the cavernous sinuses and superior ophthalmic veins. Angiography and computerised tomographic reformation techniques were used to define these extraordinary cranio-orbital venous pathways.

Adult↗
PubMed1979

Atropine versus glycopyrrolate. A study of intraocular pressure and pupil size in man.

Following control observations of intraocular pressure and pupil size, in doses suitable for pre-anaesthetic medication, glycopyrrolate (0.004 mg/kg) and atropine (0.01 mg/kg) were given intramuscularly to healthy volunteers in a randomised, cross-over fashion. No significant change in either intraocular pressure or pupil size was noted 45 min after drug administration.

Adult↗
PubMedDate not supplied

Comparison of estimates of insulin sensitivity in pre- and postmenopausal women using the insulin tolerance test and the frequently sampled intravenous glucose tolerance test.

OBJECTIVE: We assessed insulin sensitivity in women comparing the insulin tolerance test (ITT) with the intravenous glucose tolerance test with frequent sampling and computer modeling (FSIVGTT) and evaluated the effects of hormonal therapy in postmenopausal women using both methods. METHODS: This prospective study tested 18 premenopausal women and ten postmenopausal women randomized to receive either estrogen alone or estrogen with a sequential progestin for 6 months at a menopause research clinic. All subjects received an ITT and an FSIVGTT within 48-72 hours of each other in random sequence. Postmenopausal women were then randomized to receive either 0.625 mg conjugated equine estrogen for 6 months or 0.625 mg conjugated equine estrogen with medroxyprogesterone acetate, 10 mg, for 10 days each month for 6 months. Both the ITT and the FSIVGTT were repeated following hormonal therapy at 2 and 6 months. Plasma insulin and glucose were measured; insulin sensitivity was calculated after the ITT (Kitt) and the FSIVGTT (Si) at each visit in each group. RESULTS: A close correlation was found between Kitt and Si values at initial testing in both pre- and postmenopausal women and following both types of hormonal therapy (r = 0.76 for all tests, P < .001). A reduction in insulin sensitivity was observed in postmenopausal compared to premenopausal women; this occurred in five of ten postmenopausal women using the Kitt measurement and in four of ten women using Si. Estrogen replacement had a beneficial effect on insulin sensitivity. While Kitt increased by 24.2 +/- 9.6% (P < .05), the increase in Si (6.7 +/- 18%) was not significant because of the variability with this measurement. An attenuation in insulin sensitivity was seen with added progestin. Kitt values decreased by 17.7 +/- 7.7% and Si values by 31.9 +/- 12%. Similar findings were noted at 2 and 6 months. CONCLUSIONS: The ITT and FSIVGTT provide quantitatively similar information regarding insulin sensitivity in healthy women. A mild degree of insulin resistance appears to be present in some healthy postmenopausal women. Estrogen appears to improve insulin sensitivity, while added progestin may attenuate this beneficial effect.

Adult↗
PubMedDate not supplied

Duplication of the optic disc: true or pseudo? A coloboma or not a coloboma?

PURPOSE: To present an unusual case of optic disc pseudoduplication with colobomata. METHODS: Clinical evaluation, fundus photography and literature review. RESULTS: Optic disc duplication is a rare clinical entity. CONCLUSIONS: We report what we believe to be the first case of pseudoduplication of the optic disc with coexistent bilateral optic disc colobomata.

Child↗
PubMedDate not supplied

Glucose metabolism during pregnancy: normal physiology and implications for diabetes mellitus.

A remarkably coordinated set of metabolic adaptations allows the intermittently feeding mother to provide not only for her own energy needs, but also for those of the continuously feeding and developing fetus. During feeding, progressive insulin resistance and compensatory hyperinsulinemia appear to promote storage of nutrients in maternal fat and serve to "shunt" nutrients to the fetus by slowing their uptake into maternal tissues, especially during late pregnancy. Between feedings, hormones liberated by the fetoplacental unit create an environment that progressively favors maternal fat catabolism as an energy substrate source, thus curbing maternal protein catabolism while keeping some carbohydrate available for the fetus. These normal changes have important implications for women with abnormal glucoregulation. Women with pre-gestational diabetes will need progressively greater insulin doses during gestation in order to maintain normoglycemia and, in the case of women with IDDM, to avoid ketosis. Women without known diabetes may develop glucose intolerance by late gestation if their pancreatic B cells are not capable of compensating for their inherent insulin resistance and/or the normal insulin resistance of pregnancy. Norbert Freinkel was a leader in the development of our current physiological understanding of these metabolic adaptations to pregnancy. That understanding has contributed greatly to the improved outcome of pregnancies complicated by maternal diabetes. A major challenge for present and future investigators will be to develop an understanding of those adaptations at the molecular and genetic levels so that we may have even greater impact on the well-being of diabetic women and their offspring.

Blood Glucose↗