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O Castro

Publications and source records attributed to O Castro.

At least 37 records · Page 2Linked to original sources
PubMed1998

Luteal leukocytes are modulators of the steroidogenic process of human mid-luteal cells.

Flow cytometry analysis of luteal cells revealed that an important proportion of these cells are leukocytes. The percentage of leukocytes was higher in the early (42 +/- 4) and late (35 +/- 3) luteal phases than in the mid-luteal (24 +/- 2) phase. However, the proportion of macrophages did not differ between the luteal stages. The flow cytometric properties correlated with cellular size and granularity were not reliable as discriminators of luteal cell subpopulations. Therefore, to assess the contribution of luteal leukocytes, these cells were completely removed from luteal cell suspensions (total cells), by a negative selection procedure (immunomagnetic separation). The functional role of leukocytes in mid-luteal steroidogenesis was assessed, in total as well as leukocyte-depleted cells. Progesterone production was found to have increased 2.2-fold in leukocyte-depleted cell cultures, in comparison with total cells under basal conditions. However, the response to human chorionic gonadotrophin (HCG) was 36% lower under the latter conditions. Oestradiol production was not significantly modified under basal or HCG-treated conditions. In leukocyte-depleted cells, the concentration of interleukin (IL)-1beta decreased 5-fold in comparison with total cell cultures, suggesting that leukocytes are the principal source of IL-1beta. In summary, the results of the present investigation suggest functional interactions between the immune system and steroidogenic cells of the human corpus luteum.

Adult↗
PubMed1998

An in vivo model to study the anti-malaric capacity of plant extracts.

An in vivo model to study the antimalaric effect of plant extracts is described. White mice (25-30 g body weight) are treated subcutaneously with 0.6 ml of the diluted extract starting seven days before P. berghei infection; treatment continues until death or for 30 days. Simultaneously 0.2 ml of the extract are applied per os starting three days before infection. In a test of the model, treated and non-treated animals differed in body weight, survival time, haematocrite, parasitemia development, and spleen or liver weight of recent dead or killed mice.

Animals↗
PubMed1997

Acute chest syndrome in sickle cell disease: clinical presentation and course. Cooperative Study of Sickle Cell Disease.

Acute chest syndrome (ACS) is an important cause of morbidity and mortality in sickle cell disease (SCD). Previous studies reported conflicting pictures of ACS making therapeutic interventions difficult. The Cooperative Study of Sickle Cell Disease prospectively followed 3,751 patients enrolled from birth to 66 years of age for ACS. Data on presenting signs and symptoms, laboratory findings, and hospital course were collected. There were 1,722 ACS episodes in 939 patients. Young children (age 2 to 4 years) presented with fever and cough, a negative physical exam, and rarely had pain. Adults were often afebrile and complained of shortness of breath, chills, and severe pain. Upper lobe disease was more common in children; multilobe and lower lobe disease affected adults more often. Severe hypoxia occurred in 18% of adults tested and could not be predicted by examination or laboratory findings. Bacteremia was documented in 3.5% of episodes, but was strongly influenced by age (14% of infants and 1.8% of patients > 10 years). ACS was most common in winter with children having the most striking increase. Transfusion was used less frequently, but earlier in children. Young children were hospitalized for 5.4 days versus 9 days for adults. Fifty percent of adults had a pain event in the 2 weeks preceding ACS and children were more likely to have febrile events. The death rate was four times higher in adults than in children. Fatal cases generally developed rapid pulmonary failure and one third were associated with bacteremia. Age has a striking effect on the clinical picture of ACS. In children, ACS was milder and more likely due to infection, whereas in adults ACS was severe, associated with pain and had a higher mortality rate.

Adolescent↗
PubMed1997

Cancer incidence rate and mortality rate in sickle cell disease patients at Howard University Hospital: 1986-1995.

The incidence of cancer in patients with sickle cell disease (SCD) is not known. The 10-year follow-up data on 696 patients with SCD was analyzed at our institution in order to determine the cancer incidence and cancer mortality rates. The age range was 18 to 79 years, with a mean age of 28.8 years. There were 377 females and 319 males. The median follow-up was 3 years. Five patients developed cancer during this period. The cancer incidence rate was 5/2,864 or 1.74 per 1,000 patient years. The 95% CI was 0.64 to 4.32 per 1,000 patient years. There were 68 deaths with 3 being due to cancer. The cancer mortality rate was 3/2,873 or 1.04 cases per 1,000 patient years. Our data represent the first published paper that the authors are aware of, where the cancer incidence and mortality rates have been calculated for any group of patients with SCD.

Adolescent↗
PubMed1997

Evaluation of a bivalent (CVD 103-HgR/CVD 111) live oral cholera vaccine in adult volunteers from the United States and Peru.

To provide optimum protection against classical and El Tor biotypes of Vibrio cholerae O1, a single-dose, oral cholera vaccine was developed by combining two live, attenuated vaccine strains, CVD 103-HgR (classical, Inaba) and CVD 111 (El Tor, Ogawa). The vaccines were formulated in a double-chamber sachet; one chamber contained lyophilized bacteria, and the other contained buffer. In the first study, 23 U.S. adult volunteers received CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(8), 10(7), or 10(6) CFU, CVD 111 alone at 10(7) CFU, or placebo. In the second study, 275 Peruvian adults were randomized to receive CVD 103-HgR at 10(9) CFU plus CVD 111 at 10(9) or 10(8) CFU, CVD 111 alone at 10(9) CFU, CVD 103-HgR alone at 10(9) CFU, or placebo. Three of 15 U.S. volunteers who received CVD 111 at 10(7) or 10(8) CFU developed mild diarrhea, compared to none of 4 who received CVD 111 at 10(6) CFU and 1 of 4 who received placebo. Twelve (63%) of 19 vaccine recipients shed the El Tor vaccine strain. All but one volunteer developed significant Ogawa and Inaba vibriocidal antibody titers. Volunteers who received CVD 111 at 10(7) CFU had geometric mean Ogawa titers four to five times higher than those of volunteers who received the lower dose. In the second study, all dosage regimens were well tolerated in Peruvians. About 20% of volunteers who received CVD 111 at the high dose excreted the El Tor organism, compared to 7% in the low-dose group. CVD 111 was detected in the stools of two placebo recipients, neither of whom had symptoms or seroconverted. In all vaccine groups, 69 to 76% developed fourfold rises in Inaba vibriocidal antibodies. Among those who received the bivalent vaccine, 53 to 75% also developed significant rises in Ogawa vibriocidal antibodies. We conclude that it is feasible to produce a single-dose, oral bivalent vaccine that is safe and immunogenic against both biotypes (El Tor and classical) and both serotypes (Inaba and Ogawa) of cholera for populations in both developed and developing parts of the world.

Administration, Oral↗
PubMed1996

Systemic fat embolism and pulmonary hypertension in sickle cell disease.

Systemic fat embolism, a relatively rare complication of sickle cell disease, is difficult to diagnose and it is often fatal. A high index of suspicion and early transfusion therapy may provide the best chance for recovery. Sickle cell-related pulmonary hypertension can be documented by cardiac catheterization but has no proven treatment. Patients with this complication are usually adults, have a poor prognosis, and may be considered for hydroxyurea treatment. Administration of vasodilators, anticoagulation, or oxygen may be beneficial in selected individuals.

Anemia, Sickle Cell↗
PubMed1996

Hydroxyurea and sickle cell anemia. Clinical utility of a myelosuppressive "switching" agent. The Multicenter Study of Hydroxyurea in Sickle Cell Anemia.

Painful crises in patients with sickle cell anemia are caused by vaso-occlusion and infarction. Occlusion of blood vessels depends on (at least) their diameter, the deformability of red cells, and the adhesion of blood cells to endothelium. Deoxygenated sickle cells are rigid because they contain linear polymers of hemoglobin S (Hb S); polymerization is highly concentration dependent, and dilution of Hb S by a nonsickling hemoglobin such as fetal hemoglobin (Hb F) would be expected to lead ultimately to a decrease in the frequency of painful crises. It might also be expected to decrease the severity of anemia, although the pathogenesis of anemia in sickle cell anemia (SS disease) is not clearly understood. Reversion to production of fetal rather than adult hemoglobin became practical with the discovery that HU was an orally effective and relatively safe "switching agent." Preliminary dose-ranging studies led to a double-blind randomized controlled clinical trial, the Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH), designed to test whether patients treated with HU would have fewer crises than patients treated with placebo. The MSH was not designed to assess the mechanism(s) by which a beneficial effect might be achieved, but it was hoped that observations made during the study might illuminate that question. The 2 MSH treatment groups were similar to each other and were representative of African-American patients with relatively severe disease. The trial was closed earlier than expected, after demonstration that median crisis rate was reduced by almost 50% (2.5 versus 4.5 crises per year) in patients assigned to HU therapy. Hospitalizations, episodes of chest syndrome, and numbers of transfusions were also lower in patients treated with HU. Eight patients died during the trial, and treatment was stopped in 53. There were no instances of alarming toxicity. Patients varied widely in their maximum tolerated doses, but it was not clear that all were taking their prescribed treatments. When crisis frequency was compared with various clinical and laboratory measurements, pretreatment crisis rate and treatment with HU were clearly related to crisis rate during treatment. Pretreatment laboratory measurements were not associated with crisis rates during the study in either treatment group. It was not clear that clinical improvement was associated with an increase in Hb F. Crisis rates of the 2 treatment groups became different within 3 months. Mean corpuscular volumes (MCVs) and the proportion of Hb F containing red cells (F cells) rose, and neutrophil and reticulocyte counts fell, within 7 weeks. When patients were compared on the basis of 2-year crisis rates, those with lower crisis rates had higher F-cell counts and MCVs and lower neutrophil counts. Neutrophil, monocyte, reticulocyte, and platelet counts were directly associated, and F cells and MCV were inversely associated, with crisis rates in 3-month periods. In multivariable analyses, there was strong evidence of independent association of lower neutrophil counts with lower crisis rates. F-cell counts were associated with crisis rate only in the first 3 months of treatment; MCV showed an association over longer periods of time. Overall, the evidence that decreased neutrophil counts played a role in reducing crisis rates was strong. Increased F cells or MCV and evidence of cytoreduction by HU were also associated with decreased crisis rates, but no definitive statement can be made regarding the mechanism of action of HU because the study was not designed to address that question. Future studies should be designed to explore the mechanism of action of HU, to identify the optimal dosage regimen, and to study the effect of HU when combined with other antisickling agents.

Adolescent↗
PubMed1996

[Pharmacological and chemical evaluation of stachytarpheta jamaicensis (Verbenaceae)].

After intraperitoneal administration of gradual aqueous doses obtained from Stachytarpheta jamaicensis leaves, the following effects were observed in rats: a reduction of motor activity and the alarm reaction, ataxia, sedation, analgesia, anesthesia, ptosis, piloerection, head tremors and a significant reduction of body temperature of about 8.4 degrees C. Robichaud's sign was present, probably due to some muscular relaxation. There were appreciable changes on respiration, with increment on amplitudes and reduction on the frequency, followed by apnea and the death of the animals, probably due to asphysia. Iridoid ipolamiide and the phenylpropanoid glycoside, verbascoside, were identified from the same extracts. Both metabolites have been indicated with potential pharmaceuticals properties in accord with ethnobotanical value attributed to this plant.

Analgesics↗
PubMed1996

[Chemical and biological evaluation of the effect of plant extracts against Plasmodium berghei].

Extracts from thirteen species of plants were evaluated by "in vivo" antimalarial test against plasmodium berghei effects. Significant activities were observed in the ethyl acetate and aqueous extracts, elaborated of Cedrela tonduzii leaves, Trichilia havanensis and Trichilia americana barks, Neurolaena lobata and Gliricidia sepium leaves and Duranta repens fruits. Compounds identified include flavanoids, coumarins, mellilotic acid and iridoids which some kind of biodynamic activity has previously been reported. The flavone quercetin 1 purified from C. tonduzii gave strong antimalarial activity, however, its respective glucosides (quercetin 3-glucoside 2 y robinine 7) showed little significant activity.

Animals↗
PubMed1995

Multihormonal regulation of progesterone synthesis in cultured human midluteal cells.

The objectives of this investigation were to examine in vivo insulin like-growth factor-I (IGF-I) secretion by the human midcorpora lutea (mid-CL) and the effects of IGF-I, hCG, FSH, and human GH on progesterone (P) production by CL cells obtained from patients at laparotomy. We first examined whether the CL produces IGF-I by measuring IGF-I levels in the ovarian vein from the ovary bearing the CL. The IGF-I concentration in the ovarian vein bearing the CL (206 +/- 31 ng/mL) was significantly increased compared to the concentration in the contralateral ovarian vein (179.2 +/- 32 ng/mL; P < 0.05). Luteal cells isolated from mid-CL were cultured in serum-free medium 199 in the presence and absence of hCG, FSH, GH, and graded concentrations of IGF-I. At the end of the incubation period (24 h), P levels in the medium were measured by RIA. The treatment with IGF-I (0.1-10 ng/mL) showed a dose-dependent stimulatory action of IGF-I on P synthesis in the luteal cell system, being maximal between 5-10 ng/mL. The treatment with hCG (10 IU/mL), IGF-I (5 ng/mL), and GH (1000 ng/mL) increased basal P synthesis by 300%, 80%, and 30%, respectively (P < 0.001 and P < 0.05). FSH (100 ng/mL), either alone or in combination with IGF-I, failed to stimulate P synthesis. Treatment with IGF-I monoclonal antibody (1:5000) completely reduced P synthesis induced by 5 ng/mL IGF-I and slightly reduced basal P synthesis as well as GH-stimulated P synthesis by human midluteal cells. To further evaluate the specific role of IGF-I on luteal steroidogenesis, IGF-I receptor was identified by chemical cross-linking of [125I]IGF-I to mid-CL membranes. Experiments conducted in the absence and presence of unlabeled IGF-I (500 ng) revealed proteins with characteristics of the type I IGF receptor. These results are consistent with multihormonal regulation of P synthesis by the human mid-CL. hCG and IGF-I play a major role in the stimulation of P synthesis and, to a lesser extent, human GH. These in vivo and in vitro data suggest that the CL is a site of secretion, action, and reception of IGF-I during the midluteal phase.

Adult↗
PubMed1994

The acute chest syndrome in sickle cell disease: incidence and risk factors. The Cooperative Study of Sickle Cell Disease.

The acute chest syndrome (ACS), a pneumonia-like illness in sickle cell patients, is one of the most frequent causes of their morbidity and hospitalizations. Repeated ACS events may predict the development of chronic lung disease. ACS is reported as a frequent cause of death in these patients. We examine here the incidence and risk factors of ACS in 3,751 patients with sickle cell disease who were observed prospectively for at least 2 years (19,867 patient-years [pt-yrs]) as part of a multicenter national study group. The ACS, defined by a new pulmonary infiltrate on x-ray, occurred at least once in 1,085 patients (2,100 events). ACS incidence was higher in patients with homozygous sickle cell disease (SS; 12.8/100 pt-yrs) and in patients with sickle cell-beta(0) -thalassemic (9.4/100 pt-yrs), and lower in patients with hemoglobin (Hb) SC disease (5.2/100 pt-yrs) and patients with sickle cell-beta(+) thalassemia (3.9/100 pt-yrs). alpha-Thalassemia did not affect the rate of ACS incidence in SS patients. Within each Hb type the incidence was strongly but inversely related to age, being highest in children 2 to 4 years of age (25.3/100 pt-yrs in SS) and decreasing gradually to its lowest value in adults (8.8/100 pt-yrs in SS). In SS children (< 10 years of age), we documented an age-related within-person reduction in ACS attack rates. Adults with a higher ACS rate had a higher rate of mortality (from all causes) than those with low ACS rates. This increased rate of mortality might also have contributed to the decline in ACS rate with age. In multivariate analysis, other factors affecting incidence in SS patients were degree of anemia (lower ACS rates in patients with lower steady-state Hb levels) and fetal Hb (lower rates in patients with high fetal Hb). There was also a positive association between ACS rate and steady-state leukocyte count. The relationship of ACS rate to higher steady-state Hb levels in SS patients is unexplained but might be caused by increased blood viscosity.

Acute Disease↗
PubMed1994

Mortality in sickle cell disease. Life expectancy and risk factors for early death.

BACKGROUND: Information on life expectancy and risk factors for early death among patients with sickle cell disease (sickle cell anemia, sickle cell-hemoglobin C disease, and the sickle cell-beta-thalassemias) is needed to counsel patients, target therapy, and design clinical trials. METHODS: We followed 3764 patients who ranged from birth to 66 years of age at enrollment to determine the life expectancy and calculate the median age at death. In addition, we investigated the circumstances of death for all 209 adult patients who died during the study, and used proportional-hazards regression analysis to identify risk factors for early death among 964 adults with sickle cell anemia who were followed for at least two years. RESULTS: Among children and adults with sickle cell anemia (homozygous for sickle hemoglobin), the median age at death was 42 years for males and 48 years for females. Among those with sickle cell-hemoglobin C disease, the median age at death was 60 years for males and 68 years for females. Among adults with sickle cell disease, 18 percent of the deaths occurred in patients with overt organ failure, predominantly renal. Thirty-three percent were clinically free of organ failure but died during an acute sickle crisis (78 percent had pain, the chest syndrome, or both; 22 percent had stroke). Modeling revealed that in patients with sickle cell anemia, the acute chest syndrome, renal failure, seizures, a base-line white-cell count above 15,000 cells per cubic millimeter, and a low level of fetal hemoglobin were associated with an increased risk of early death. CONCLUSIONS: Fifty percent of patients with sickle cell anemia survived beyond the fifth decade. A large proportion of those who died had no overt chronic organ failure but died during an acute episode of pain, chest syndrome, or stroke. Early mortality was highest among patients whose disease was symptomatic. A high level of fetal hemoglobin predicted improved survival and is probably a reliable childhood forecaster of adult life expectancy.

Adult↗
PubMed1994

Enhancement of pain control with ketorolac tromethamine in patients with sickle cell vaso-occlusive crisis.

Twenty one patients with sickle cell disease admitted to the hospital with the pain of vaso-occlusive crisis (VOC) were treated by continuous IV infusion of ketorolac or normal saline for up to 5 days. All patients received supplemental IM injections of meperidine, 100 mg, as necessary, but not more frequently than every 3 hr. Over the 5 days the ketorolac treated patients (KT) required 33% less meperidine than did the placebo treated patients (PL), P = 0.04, and had significantly better pain relief as assessed by categorical, visual analog, and pain relief scales. By the end of 5 days infusions had been discontinued in six KT and one PL. The time to discontinuation of the infusion was significantly shorter in KT, (P = 0.009). The median duration of hospital stay from the start of treatment was 3.3 days for KT and 7.2 days for PL, P = 0.027. Adverse events were mainly related to the digestive system. This study showed that continuous infusion of ketorolac significantly reduced total meperidine requirement and that the analgesia produced by this combination was superior to that produced by meperidine alone. Further evaluation of this drug in the management of sickle cell VOC is warranted.

Adult↗
PubMed1994

Improvement of sickle cell anemia by iron-limited erythropoiesis.

We report the hematologic and clinical features of four adult patients (Pts.) with sickle cell anemia and iron-limited erythropoiesis. Two of the Pts. had spontaneous iron deficiency (chronic GI bleeding, low-grade hemoglobinuria). In the other two Pts. iron restriction was induced by periodic RBC aphereses as part of a pilot protocol designed to decrease intracellular HbS polymerization by MCHC reduction. Iron-limited erythropoiesis was defined by reduction in red cell indices (MCV range 60.4-67 fl) in the presence of low serum ferritin (range < 10-20 ng/ml). In these Pts. iron restriction did not cause clinically significant worsening of the anemia (Hb 7.8-9.0 g/dl). In two Pts. the anemia actually improved. Other hematologic effects of iron restriction were: decreased MCHC, reticulocyte count, RDW, and dense cells. A reduced hemolytic rate was suggested by a lowering of serum bilirubin and LDH. In one of the Pts. the 51Cr RBC T1/2 survival increased from 12 to 16 days. The intracellular HbS polymer fractions (fp) were determined at 25% O2 by Csat and with the use of the conservation of mass equation. The baseline fp values ranged from 0.48-0.53. After iron restriction they ranged from 0.33-0.48. The fp decreased even though iron-limited erythropoiesis also lowered the Hb F concentration in three of our Pts. In one of the two Pts. with induced iron depletion, hospitalization days for pain crises decreased from an average of 4.5 days/month (2 year baseline period) to an average of 0.5 days/month in the 3 year follow-up after iron depletion. The second patient with induced iron restriction experienced the rapid healing of a leg ulcer. Controlled iron restriction should be explored as a therapeutic strategy in selected SS patients.

Adult↗
PubMed1994

Progesterone synthesis by human luteal cells: modulation by estradiol.

To assess the role of estradiol (E2) upon progesterone (P4) synthesis, a well defined human midluteal cell system was used. A dose-dependent inhibition of P4 synthesis with and without hCG was induced by E2. In addition, E2 had a dose related cumulative effect on pregnenolone as compared with control experiments (2-fold, P < 0.05) as well as in hCG-stimulated conditions (3-fold, P < 0.005). On the other hand, the concentrations of 20 alpha-hydroxyprogesterone obtained in all experimental conditions were similar to control values, indicating that the catabolism of P4 was not modified. 3 beta-Hydroxysteroid dehydrogenase activity was significantly diminished (P < 0.05) in the presence of E2. Finally, the kinetic studies on P4 synthesis from pregnenolone showed a competitive type of inhibition with a K1 of 2.22 x 10(-6) mol/L. These data indicate an inhibition of 3 beta-hydroxysteroid dehydrogenase on human corpus luteum by E2.

20-alpha-Dihydroprogesterone↗
PubMed1993

G gamma A gamma (beta+) hereditary persistence of fetal hemoglobin: the G gamma -158 C-->T mutation in cis to the -175 T-->C mutation of the A gamma-globin gene results in increased G gamma-globin synthesis.

Hereditary persistence of fetal hemoglobin (HPFH) can be generally classified into deletional and nondeletional forms. The family described in the present study has characteristics of both types of HPFH. The proband is a healthy 30-year-old black woman. Analysis of her hemoglobin revealed 40.4% HbS, 40.9% HbF (G gamma/A gamma ratio 0.53), 16.8% HbA, and 1.9% HbA2. All of her hematologic indices were normal, and the distribution of HbF in her red cells was pancellular. Family studies demonstrated that the proband has one chromosome 11 bearing the beta s-globin gene and the other bearing a G gamma A gamma (beta+) HPFH determinant in cis to the beta A-globin gene. Gene mapping studies of the region between the G gamma- and beta-globin genes were normal. However, when the A gamma and G gamma promoters were amplified by polymerase chain reaction (PCR) and sequenced, the A gamma promoter was found to have the T-->C mutation at -175, and the G gamma promoter region was found to have the C-->T mutation at -158. The -158 C-->T mutation has been associated with elevated G gamma levels and high HbF in hemolysis, although its role in causing these effects is unclear. The present study suggests that this mutation can also enhance G gamma-globin expression in cis to the -175 T-->C mutation in the absence of hemolysis. We suggest that the alteration of the A gamma gene octamer binding site by the -175 mutation, as well as the loss of a putative G gamma "silencer" caused by the -158 mutation may account for this phenotype. We propose calling these linked mutations the G gamma A gamma(beta+) HPFH.

Adult↗