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Biomedical subjects

R A Simmons

Publications and source records attributed to R A Simmons.

26 records · Page 2Linked to original sources

Circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) and hepatic mRNA are increased in the small for gestational age (SGA) fetal rat.

Insulin-like growth factors (IGFs) circulate in association with a family of specific binding proteins (BPs). Recently, we reported that circulating levels of IGFBP-1 and IGFBP-2 are increased in streptozotocin-diabetic adult rats and are differentially regulated in accordance with insulin and metabolic status. Since IGF BPs appear to be important modulators of IGF bioactivity in post-natal life, we asked whether serum levels of IGF BPs also might be altered in utero when the delivery of maternal nutrients is restricted and fetal growth is impaired. Bilateral uterine artery ligation or sham surgery was performed on maternal rats on d 19 of gestation (term 21.5 d). One day after ligation (d 20), fetuses were (SGA) compared to shams (3.1 +/- 1 vs 3.7 +/- 0.2 g, p less than .02) and serum levels of glucose (70 +/- 5 vs 96 +/- 6 mg/dL, p less than .01) and insulin (62 +/- 4 vs 138 +/- 14 microU/mL) also were reduced. In contrast, serum [125I]IGF-I binding activity was markedly increased in SGA litters compared to sham (65 +/- 5% maximum binding with 2.5 microL/mL SGA serum vs 14 +/- 3% for sham serum, p less than .001), and correlated with fetal weight (r = -0.539, p less than .05) and insulin (r = -0.622, p less than .05). Ligand blotting with [125I]IGF-I revealed that serum levels of IGFBP-1 (32 K) were greater in SGA than shams, while immunoblotting with specific antiserum demonstrated that levels of IGFBP-2 (34 K), the major fetal rat IGF BP, were similar in serum from SGA and shams litters. Affinity labeling and immunoprecipitation confirmed that IGF binding activity is increased in SGA, due largely to increased availability of IGFBP-1. In addition, Northern analysis of hepatic RNA revealed that the abundance of IGFBP-1 mRNA is increased in the SGA fetal rat, while hepatic mRNA for IGFBP-2 is similar in SGA and sham-operated litters. We conclude that circulating levels of IGFBP-1 and the abundance of hepatic mRNA are increased in the SGA fetal rat. IGFBP-1 may be an important modulator of IGF bioactivity and somatic growth in utero.

Affinity Labels↗

Substrate utilization by the fetal sheep lung during the last trimester.

In vivo substrate utilization has not been described for the maturing fetal lung. We, therefore, studied pulmonary delivery and use of major fetal substrates in six chronically catheterized fetal lambs over 119-141 days gestation. Oxygen, glucose, lactate, and alpha-amino nitrogen concentrations were measured in the pulmonary artery and pulmonary vein whereas lung blood flow was determined using labeled microspheres. We found that lung oxygen availability and use increased near term. Oxygen delivery averaged 4960 +/- 480 (SEM) microliters/min and rose with fetal age (p less than 0.05); uptake averaged 708 +/- 111 microliters/min and increased 93% near term (p less than 0.05). In contrast, glucose availability and use fell with gestation. Pulmonary artery glucose decreased with time (p less than 0.001), with a mean drop of 5.05 +/- 1.71 mg/dl in individual animals (p less than 0.05). Average glucose uptake was 844 +/- 225 micrograms/min and fell near term (p less than 0.05). Lactate was produced by the lung at a mean rate of 534 +/- 176 micrograms/min; this did not change with gestation. Lung amino nitrogen availability increased with fetal age. Pulmonary artery amino nitrogen rose by 1.35 mg/dl, or 43% (p less than 0.001) and lung delivery of amino nitrogen increased (p less than 0.05). The mean pulmonary glucose/O2 ratio was 1.48 +/- 0.26 and decreased with gestation (p less than 0.05), being less than 1.0 near term. The glucose-lactate/O2 ratio was 0.67 +/- 0.26, implying that 30% of lung oxidative metabolism is still unaccounted for. The alterations in delivery of substrates to the lung which were identified may serve as signals for pulmonary maturation, inducing the changes in lung metabolism that were found near term.

Animals↗

An outbreak of amebiasis spread by colonic irrigation at a chiropractic clinic.

From June 1978 through December 1980, at least 36 cases of amebiasis occurred in persons who had had colonic-irrigation therapy at a chiropractic clinic in western Colorado. Of 10 persons who required colectomy, six did. Of 176 persons who had been to the clinic in the last four months of 1980, 80 had received other forms of treatment. Twenty-one per cent of the colonic-irrigation group had bloody diarrhea, as compared with 1 per cent of the non-irrigation group (P = 0.00013). Thirty-seven per cent of the colonic-irrigation group who submitted specimens had evidence of amebic infection on either stool examination or serum titer, as compared with 2.4 per cent in the non-irrigation group (P = 0.00012). Persons who were given colonic irrigation immediately after a person with bloody diarrhea received it were at the highest risk for the development of amebiasis. Tests of the colonic-irrigation machine after routine cleaning showed heavy contamination with fecal coliform bacteria. The severity of disease in this outbreak may have been related to the route of inoculation.

Adult↗

Unrecognized intraoperative torsion of the lung.

A case is presented of clockwise torsion of the entire left lung on its bronchovascular pedicle during intraoperative manipulations for a nonpulmonary procedure. The grave consequences are presented as well as a discussion of the mechanism of injury and a review of the pertinent literature. To our knowledge, this is the first such case reported.

Esophageal Achalasia↗

Skin lesions in paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon hemolytic anemia that rarely manifests skin lesions. Leg ulcers and purpura similar to the manifestation of thrombotic thrombocytopenic purpura (TTP); disseminated intravascular coagulation, and Henoch-Schönlein purpura do occur. This is the second known case report of PNH with histopathologic features of TTP. Clinically, our patient's condition resembled TTP with disseminated intravascular platelet aggregation, and she followed a nonfulminant course. She improved on a regimen of systemic steroids, dipyridamole, and cessation of antibiotics.

Adult↗