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Biomedical subjects

J F Garcia

Publications and source records attributed to J F Garcia.

At least 73 records · Page 4Linked to original sources
PubMed1984

Effects of oxygen inhalation on endogenous erythropoietin kinetics, erythropoiesis, and properties of blood cells in sickle-cell anemia.

The role of oxygen therapy in sickle-cell anemia is not established, and its effects on erythropoiesis and on the rheologic properties of sickled erythrocytes are controversial. When three patients with sickle-cell anemia who were not in crisis or infected breathed oxygen at a rate of 5 liters per minute continuously through nasal prongs for five days, there was a rapid decline in erythropoietin levels that had initially been elevated, a delayed fall in the number of reticulocytes, and a fall in the number of irreversibly sickled cells, which, in two of the subjects, preceded the suppression of reticulocytosis. After cessation of oxygen therapy, erythropoietin levels and the number of irreversibly sickled cells increased promptly, followed by an increase in the number of reticulocytes. Calculated erythropoietin half-lives were 1.51 to 2.92 hours, and clearances were 43 to 84 ml per minute during oxygen administration. These are normal values. In two subjects, the number of irreversibly sickled cells rose to exceed base-line values after oxygen therapy was discontinued, and both subjects had acute painful episodes at this time. We conclude that in patients with sickle-cell anemia, substantial changes in erythropoiesis and in the rheologic properties of blood occur in association with oxygen inhalation and that when oxygen therapy is administered to such patients, it should be given intermittently rather than continuously.

Anemia, Sickle Cell↗
PubMed1984

Plasma immunoreactive erythropoietin in normal women studied sequentially during and after pregnancy.

Six healthy, nonanemic women with uncomplicated singleton pregnancies were sequentially studied for plasma immunoreactive erythropoietin levels, hematologic indices, and human placental lactogen. Mean group levels of erythropoietin as well as human placental lactogen were significantly increased (p less than 0.01) after 18 weeks' gestation compared to nonpregnant values (20 to 30 weeks post partum). However, individual responses of erythropoietin during pregnancy were found to be highly variable. There was a direct correlation of both maternal plasma erythropoietin and human placental lactogen with gestational age (p less than 0.001) but no detectable relation of erythropoietin with human placental lactogen levels. We speculate that the increase in erythropoietin levels during pregnancy acts as a trophic stimulus for effecting an increase in maternal red blood cell mass presumably to meet the increased metabolic (oxygen) demands of pregnancy.

Adult↗
PubMed1984

Increased immunoreactive erythropoietin in cord serum after labor.

Since several hours of hypoxemia in fetal animals is sufficient to cause an increase in the plasma erythropoietin level and since labor may be associated with fetal hypoxemia, this study was undertaken to determine if erythropoietin levels in cord blood were higher in fetuses subjected to labor. Two groups of term (37 to 41 weeks) singleton pregnancies were compared: (1) those delivered by elective repeat cesarean section without prior labor (n = 18) and (2) those delivered vaginally (n = 23). Erythropoietin was measured by a radioimmunoassay in which a highly purified human erythropoietin (70,000 U/mg of protein) was used and which has a sensitivity limit of 4 to 5 mU/ml. The mean cord serum erythropoietin level was higher in pregnancies with labor (46 +/- 34 mU/ml, mean +/- SD) compared to those without (26 +/- 10, p less than 0.02). There were no differences between the two groups for maternal age, gestational age, birth weight, infant sex, or Apgar scores. No association of erythropoietin with either gestational age or sex was found. In 11 pregnancies without labor, comparisons were made among simultaneously obtained samples of umbilical arterial plasma, umbilical venous plasma, and mixed cord serum. Although there were no differences between umbilical arterial and umbilical venous plasma erythropoietin levels (21.3 +/- 9.3 versus 19.0 +/- 7.8 mU/ml), mixed cord serum was inexplicably higher (24.4 +/- 9.5 mU/ml, p less than 0.01). We concluded that in uncomplicated pregnancies the duration and intensity of labor are sufficient to cause an increase in the fetal erythropoietin level at delivery.

Adolescent↗
PubMed1984

Anemia of prematurity: determinants of the erythropoietin response.

This study was undertaken to determine the factors that are important in determining the erythropoietin response in low-birth-weight infants during the period of so-called anemia of prematurity. In the first weeks of life oxygen consumption in a group of 21 infants gradually increased as hemoglobin level fell. The magnitude of the erythropoietin response inversely varied with the central venous oxygen tension (P-vO2) (r = -0.55, P less than 0.001). When the P-vO2 declined to less than 30 torr, erythropoietin values were uniformly increased above the "normal" range (defined as the values associated with P-vO2 greater than 38 torr). Erythropoietin values varied inversely with hemoglobin but in general did not exceed the values observed for normal adult men. The erythropoietin values in the infants were remarkably lower at any given hemoglobin level when compared with those of older children with anemia resulting from bone marrow failure. In general, elevations of erythropoietin were seen when the hemoglobin concentration declined to less than 10.0 gm/dl. Change in heart rate did not appear to be a reliable indicator of the presence of anemia; rather, it correlated best with oxygen consumption.

Adult↗
PubMed1984

Decreased response of plasma immunoreactive erythropoietin to "available oxygen" in anemia of prematurity.

Erythropoietin, hemoglobin, hematocrit, oxygen affinity (P50), and reticulocyte counts were measured weekly starting at 1 week of age in 10 very-low-birth-weight infants and on a single occasion in 15 healthy men. In the adults, "available oxygen" (derived from oxygen carrying capacity and P50) averaged 13.1 ml/dl blood and the mean erythropoietin level was 15.2 mU/ml. Erythropoietin levels in the infants were inversely related to concentration of hemoglobin, P50, and available oxygen. However, despite the much lower mean "available oxygen" of 9.3 ml/dl in the infants compared with that in adults (P less than 0.001), the mean erythropoietin value of 8.2 mU/ml in the infants was less than in adults (P less than 0.001). Furthermore, the erythropoietin response to decreased "available oxygen" was lowest in the least mature infants. VLBW infants often develop clinical evidence of hypoxia during the anemia of prematurity. The relatively low erythropoietin levels in relation to "available oxygen" are compatible with a decreased erythropoietin response to hypoxia compared with that in adults. Such a difference in response could be a contributing factor to the anemia of prematurity.

Adult↗
PubMed1984

Pulmonary excretion of carbon monoxide in the human infant as an index of bilirubin production. IIc. Evidence for the possible association of cord blood erythropoietin levels and postnatal bilirubin production in infants of mothers with abnormalities of gestational glucose metabolism.

A total of 20 infants who had levels of erythropoietin (Ep), the major hormone regulating erythropoiesis, measured in their cord blood also had determinations of the pulmonary excretion rate of CO (VECO) performed, as an index of total bilirubin production. They were either infants of normal mothers or those of mothers with diabetes, gestational diabetes, and missed abnormalities of gestational glucose metabolism. The mean VECO (13.0 +/- 3.5 mu 1/kg/hr) and the mean Ep (20.0 +/- 9.7 SD mU/ml) of the infants with normal mothers (n = 9) were not different from the means previously established by our laboratories (13.9 +/- 3.5 SD mu 1/kg/hr, n = 20; and 23.7 +/- 12.8 SD mU/ml, n = 30, respectively); they were significantly lower than those of the infants of the abnormal mothers in this study. The 5 infants who had a cord blood Ep level greater than 50 mU/ml had a higher mean VECO, 27.8 +/- 7.1 mu 1/kg/hr, compared with 17.2 +/- 4.9 SD mu 1/kg/hr, of the six infants with cord blood Ep levels that were within 2 SD of the previously established normal mean cord blood Ep level (p less than .025). These data suggest that increased cord blood Ep levels and postnatal bilirubin production in infants whose mothers had abnormalities of gestational glucose metabolism are associated phenomena. Since polycythemia did not occur in these infants, ineffective erythropoiesis or mild, compensated hemolysis remains a likely cause of the increased total bilirubin production. In some cases, perinatal hypoxic stress may have affected the Ep response.(ABSTRACT TRUNCATED AT 250 WORDS)

Bilirubin↗
PubMed1984

The anaemia of chronic renal failure in sheep: studies in vitro.

The presence of inhibitors which accumulate during uraemia has been postulated as a significant factor in the development of anaemia in chronic renal failure (CRF). To determine whether factors in uraemic serum depress erythropoiesis, samples were obtained from sheep prior to and after surgical induction of CRF. The sera were tested in vitro for their effect on erythroid colony growth. The sheep sera were substituted for fetal calf serum (30% concentration) in cultures of serotype-matched or autologous sheep marrow cells at optimal doses of erythropoietin (Ep). Forty-two paired sera from five animals were tested against normal (22) and uraemic marrow (20). In 7/42 random pairs, erythroid colony growth was decreased by 20% in the presence of uraemic serum when compared to a normal sample from the same animal. In the remainder of the cultures, uraemic sera stimulated or supported erythroid colony growth as well as normal sera. When the results were analysed individually, serum from only one of five animals showed minimal (10%) in vitro inhibition of erythroid colony growth. This study, performed in a prospective manner utilizing compatible target cells, disputes the hypothesis that uraemic toxins significantly inhibit in vitro erythropoiesis. These data correlate with the in vivo response to Ep in this sheep model, and suggest Ep would be effective in treating the anaemia of CRF.

Anemia↗
PubMed1984

The anemia of chronic renal failure in sheep. Response to erythropoietin-rich plasma in vivo.

The hypoproliferative anemia in chronic renal failure has been assumed to be the result of decreased erythropoietin (Ep) production by the damaged kidney and of the shortening of erythrocyte survival. However, many in vitro studies suggest that erythropoietic inhibitors in uremic plasma may contribute to the anemia. To determine the in vivo relevance of uremic inhibitors, increasing amounts of Ep as Ep-rich plasma were infused into six uremic sheep, and their erythropoietic responses were compared with those of nine normal sheep receiving similar amounts of Ep-rich plasma. Three sheep were studied in both normal and uremic states. Ep-rich plasma was obtained from phenylhydrazine- and phlebotomy-induced anemic sheep. Stable uremia was created by subtotal nephrectomy. Erythropoiesis was quantitated by reticulocyte response, ferrokinetics (plasma iron turnover and marrow transit time), and by hemoglobin C synthesis. Ep-rich plasma stimulated erythropoiesis similarly in uremic and normal sheep, regardless of the degree of uremia. Nondialyzed uremic sheep responded as well as dialyzed animals. The anemia was corrected in the uremic dialyzed animals. The anemia was corrected in the uremic sheep after 15-40 daily infusions of Ep-rich plasma, the total dosage depending on the severity of the anemia. Polycythemia was induced when the infusions were continued. Reticulocytes, plasma iron turnover, and erythrocyte mass changes increased as the amount of Ep-rich plasma was increased. These dose-response effects, coupled with the identical erythropoietic response in normal and uremic sheep given the same amount of Ep-rich plasma, imply that there are no physiologically significant erythropoietic inhibitors in uremia.

Anemia↗
PubMed1984

Secretion of erythropoietin-like activity by clones of human renal carcinoma cell line GKA.

Human renal carcinoma cell line GKA was derived from a patient with the paraneoplastic syndrome of erythrocytosis and secretes erythropoietin-like activity into its growth medium (Sytkowski, A. J., Richie, J. P., and Bicknell, K. A. Cancer Res., 43: 1415-1419, 1983). In order to derive homogeneous sublines with higher secretory rates, we cloned line GKA. Over 100 clones were generated, and 21 secreted erythropoietin-like activity, up to 6-fold higher than the uncloned line. This activity stimulated the growth and differentiation of CFU-E derived colonies in plasma clot culture. However, the secreted erythropoietin-like activity did not cross-react in a sensitive radioimmunoassay utilizing highly purified 125I-labeled human urinary erythropoietin and heterologous anti-human urinary erythropoietin antiserum. These results suggest that line GKA secretes an erythropoietic stimulating factor distinct from the hormone erythropoietin.

Cell Line↗
PubMed1983

Postnatal changes in erythropoietin levels in untransfused premature infants.

The purpose of this study was to determine whether an inappropriately low erythropoietin response in premature infants might be a basis for the anemia of prematurity. Erythropoietin was measured by radioimmunoassay in conjunction with hemoglobin and reticulocyte count in untransfused premature infants between birth and 60 days of age. The 27 infants had a mean gestational age of 31 weeks and a mean birth weight of 1378 gm. Between 2 and 30 days, mean erythropoietin concentration was 9.7 mU/ml, significantly and substantially lower than 15.2 mU/ml in 15 concurrently studied healthy adults (P less than 0.01). Subsequently, from 30 to 60 days, values rose gradually to a mean of 17.2 mU/ml, which did not differ significantly from the mean value in adults. Hemoglobin values fell from a mean of 12.9 gm/dl during the first month to 9.0 gm/dl between 30 and 60 days. Thus, during the second postnatal month, preterm infants had essentially the same erythropoietin values as in adults despite a mean hemoglobin concentration that averaged less than two thirds the adult value. This failure to mount a greater erythropoietin response may help to explain why hemoglobin declines to such low values at 2 months of age.

Aging↗
PubMed1983

Anticrossover emulsions evaluated by observer performance tests.

Observer performance in the detection of pulmonary nodules and infiltrates was measured using film coated with anticrossover emulsion, a recent innovation in radiographic film that is expected to produce sharper images because of improved resolution. Test radiographs of an anthropomorphic phantom were shown to six experienced observers. Radiographs containing pseudonodule and pseudoinfiltrate images were obtained with the anticrossover film and the same type of film without the anticrossover coating. Test images contained single nodules, single infiltrates, or both; approximately 45% of the test radiographs were normal. Individual receiver operating characteristic (ROC) curves were formed, and sensitivity and specificity values were calculated. The results demonstrated an improvement in observer performance with the anticrossover film as measured by sensitivity and the area under the average ROC curves.

Humans↗
PubMed1982

Radionuclide bone scan, radiographic bone survey, and alkaline phosphatase: studies of limited value in asymptomatic patients with ovarian carcinoma.

Bone scans or skeletal surveys were obtained in 104 patients with ovarian carcinoma. No metastases were identified at staging in the 43 patients with Stage I or II disease. Four patients in the entire series had osseous metastases. Three of the 40 patients with Stage III epithelial ovarian carcinoma had osseous metastases at the time of staging. All of these were Grade III lesions. One Stage I, Grade III patient demonstrated osseous metastases two years after initial diagnosis. None of the four patients with osseous metastases had an elevated alkaline phosphatase; three of the four had bone pain. Based on these results, it is suggested that radiographic bone survey and radionuclide bone scans are not indicated as screening procedures in asymptomatic patients with ovarian carcinoma.

Alkaline Phosphatase↗
PubMed1982

Utility of radionuclide liver/spleen scanning and serum enzyme level in detecting hepatic metastases from ovarian carcinoma.

One hundred-five patients with ovarian carcinoma had radionuclide liver/spleen scanning done at the time of staging. Of the 105 initial scans, eight were interpreted as having hepatocellular dysfunction. Seven of these eight had abnormal liver function studies. One patient had a hepatic cyst but had elevated liver function studies. Six patients demonstrated hepatic metastases (at the time of staging). All but one of these occurred in Stage IV tumors of epithelial origin (adenocarcinoma). No hepatic metastases were demonstrated in Stage I or II tumors, and only one Stage III epithelial carcinoma had hepatic metastases. Three patients developed hepatic metastases during the course of treatment. All nine patients with hepatic metastases had abnormal concurrent liver function studies. It is suggested that screening for liver metastases in patients with ovarian carcinoma is of limited value in patients with normal liver function studies.

Alkaline Phosphatase↗
PubMed1982

Plasma levels of immunoreactive erythropoietin after acute blood loss in man.

Plasma levels of immunoreactive erythropoietin (Ep) were measured after acute blood loss (50, 75, 200 and 450 ml) in man in order to determine the volume of blood loss required to trigger an Ep response as well as to define the reticulocyte response. There was a highly significant (P less than 0.01) linear increase in reticulocyte count after 200 and 450 ml of blood loss. Analysis of trends also showed a highly significant (P less than 0.01) linear response of haematocrit and Ep after a 450 ml blood loss. The reticulocyte count increases were not dependent on a prior increase in Ep level indicating that at least two mechanisms are operative in restoring the red cell mass to normal after blood loss.

Adult↗