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D Medeiros

Publications and source records attributed to D Medeiros.

At least 19 recordsLinked to original sources
PubMed2007

Short-term oral corticosteroid therapy for acute haemarthrosis in haemophilia patients with high-titre inhibitors.

Treatment of acute bleeding events is unsatisfactory in patients with haemophilia and high-titre factor VIII (FVIII) inhibitors. In order to determine whether short-term corticosteroid therapy enhances resolution of the signs and symptoms of acute haemarthrosis, we performed a randomized, double-blind, placebo-controlled study in children with FVIII deficiency and high-titre inhibitors receiving Factor Eight Inhibitor Bypass Activity (FEIBA) for acute haemorrhagic events. At each haemarthrosis, patients were randomized to receive either prednisolone 2 mg kg(-1) day(-1) or placebo-divided t.i.d. for 2 days (six doses) in addition to FEIBA. The primary endpoint was the number of subsequent doses of FEIBA required. The effect of the study medication was also assessed subjectively by patients or parents, by physical examination and by repeated haemorrhages into the joint. During the study period, seven patients were enrolled with 45 evaluable events, 24 treated with prednisolone and 21 with placebo. An average of 2.08 and 1.86 doses of FEIBA were infused in the prednisolone- and placebo-treated patients, respectively. By Wilcoxon Rank Sum Test, there was no statistically significant difference in number of additional infusions of FEIBA or duration of symptoms between the corticosteroid and placebo arms. We conclude that there is no significant benefit of a 2-day course of oral corticosteroids as adjunctive therapy for haemarthrosis in patients with haemophilia and a high-titre inhibitor.

Adolescent↗
PubMed2001

Catheter-related thrombosis in children with cancer.

OBJECTIVE: The prevalence of asymptomatic catheter-related thrombosis of the upper venous system in children with cancer has not been determined. We evaluated patients with cancer and implantable central venous catheters (ports) for this complication. STUDY DESIGN: Children with cancer undergoing port removal were eligible for this study. Vessel patency was evaluated by contrast venography. We examined each child for physical stigmata of thrombosis and retrospectively assessed catheter-related mechanical difficulties and infections. RESULTS: Thirty-one ports had been placed in 24 children (aged 20 months to 18 years; median age, 9 years) with diagnoses of leukemia/lymphoma (n = 10), solid tumor (n = 12), and histiocytosis (n = 2). Venography showed abnormalities in 12 of the 24 patients. Physical examination revealed dilated superficial veins on the chest in 3 patients. Venograms showed abnormalities in all 3 children with prominent superficial thoracic veins. Nine of the 21 other patients had clinically occult central venous occlusion. CONCLUSION: Fifty percent (95% CI, 30% to 70%) of children who had implantable ports removed during or after treatment of cancer exhibited deep venous thrombosis at the site of catheter placement. Future studies should determine the contribution of inherited and other acquired risk factors for thrombosis and assess measures to prevent and/or treat catheter-related thrombosis in this population.

Adolescent↗
PubMed2000

Oxidative stress-induced apoptosis of endothelial cells.

Endothelial cells (ECs) are subjected to oxidative stress during many pathological processes, including ischemia/reperfusion and general inflammation. In the present study, we examined the effects of oxidative stress on rates of apoptosis in EC cultures. We treated large and microvessel ECs with menadione for 1 h in vitro to simulate the most common physiological form of oxidative stress, exposure to O2*-. Capillary ECs were resistant to menadione-induced apoptosis when compared with large-vessel ECs. Treatment with 35 microM menadione resulted in an apoptotic rate of approximately 5% in capillary EC cultures compared with approximately 45% in large-vessel EC cultures. At higher concentrations of menadione (35-75 microM), both types of ECs exhibited a concentration-related increase in apoptosis. Necrotic cell death only became evident at menadione concentrations ranging from 75-100 microM for both cell types. The timing of the apoptotic response to a 1 h menadione exposure was very specific. For both EC types, peaks of apoptosis occurred in two distinct waves, at 6-8 and 18-22 h after treatment. Analysis of the events leading up to the first peak of apoptosis indicated that specific matrix metalloproteinases (MMPs) were activated, suggesting that MMPs may be involved in initiating the apoptotic process.

Animals↗
PubMed2000

Reported adoption of dietary fat and fiber recommendations among consumers.

OBJECTIVE: To identify constraints in adopting dietary fat and fiber recommendations. DESIGN: A questionnaire was mailed to a sample of the general population, a convenience sample of persons with heart disease and cancer in 11 states, and registered dietitians in 5 states. The survey included questions on demographic and attitudinal factors that were correlated with specific practices to reduce fat intake and increase fiber intake. SETTING: From the general population sample of 6,206 eligible respondents (return rate of 51.5%), those selected were respondents who indicated that they would adopt a dietary recommendation if it were good for them (n = 2,682). Subsamples from the general population were matched to 362 registered dietitians and 147 persons with cancer or heart disease on selected demographic variables. Factors associated with adoption of specific behaviors were identified. STATISTICAL ANALYSIS PERFORMED: Statistical analysis included chi 2, factor analysis, and analysis of variance. RESULTS: The majority of persons who said they would adopt a fat-reducing behavior if it were good for their health reported practicing that behavior often or usually. More than 60% reported consuming whole grains; however, only 15% reported eating fruits and vegetables frequently. Among the general population sample, those more likely to practice a behavior had the following characteristics: female, college educated, older than 60 years, white, higher income, no children younger than 18 years, perceived health status as excellent, and absence of chronic disease. Registered dietitians and those with chronic disease were also more likely to follow dietary fat and fiber recommendations. APPLICATIONS: Nutrition education messages that lead to increased consumption of dietary fiber need to be developed. Nutrition educators should provide strategies for consumers for increasing use of fruits and vegetables in all meals. Good taste and convenience are critical components. The food industry may assist by providing a wider array of convenience entrees or side dishes that feature produce and whole grains.

Adult↗
PubMed2000

Idiopathic thrombocytopenic purpura: beyond consensus.

Idiopathic thrombocytopenic purpura (ITP) is the most common acquired bleeding disorder encountered by pediatricians. Most children with ITP have minimal bleeding and complete platelet count recovery within weeks to months. Therapy for ITP has ranged from close observation without medical intervention to aggressive management with corticosteroids, intravenous immunoglobulin G, or anti-D immune globulin. The topic of ITP has incited great debate among practitioners, and this debate prompted the development of ITP practice guidelines by the British Paediatric Haematology Group in 1992 and by the American Society of Hematology in 1996. A better understanding of the clinical course of, risk for significant bleeding in, and optimal evaluation and therapy of childhood ITP will require carefully designed, multicenter, clinical trials.

Child↗
PubMed1998

Major hemorrhage in children with idiopathic thrombocytopenic purpura: immediate response to therapy and long-term outcome.

OBJECTIVES: We retrospectively characterized children with idiopathic thrombocytopenic purpura (ITP) who had major hemorrhage to determine response to therapy and long-term outcome. STUDY DESIGN: We reviewed the medical records of 332 children with ITP diagnosed at our center during the last 10 years for occurrence of major hemorrhage, defined as (1) intracranial hemorrhage, (2) epistaxis requiring cautery or nasal packing, (3) gross hematuria, or (4) other bleeding causing a decline in hemoglobin concentration. RESULTS: Of 332 patients with ITP, 58 (17%) had 68 episodes of major hemorrhage; 56 of these episodes were treated with corticosteroids, intravenous immunoglobulin, or both. The platelet count rose to > or =20,000/mm3 within 24 hours after presentation after only 18% of evaluated events, and 28% of patients with major hemorrhage still had a platelet count <20,000/mm3 after 7 days. Twenty-seven of 49 patients available for evaluation had resolution of ITP within 6 months, 21 had chronic ITP, and 1 died of sepsis. CONCLUSIONS: We observed that 17% of children with ITP had major hemorrhage. Only a minority of these patients had an immediate rise in platelet count after receiving intravenous immunoglobulin, corticosteroid treatment, or both. Prospective studies of childhood ITP focusing on short-term outcome variables in addition to platelet count should be performed to better define optimal treatment for each affected child.

Adolescent↗
PubMed1998

Implantable venous access devices in children with hemophilia: a report of low infection rates.

OBJECTIVE: The objective of this study was to define the efficacy and complications of implantable venous access devices (IVADs) in children with hemophilia. STUDY DESIGN: Records were reviewed on all patients with congenital blood coagulation disorders monitored at two children's hospitals in whom one or more central venous catheters had been placed. RESULTS: Since 1989 external and implantable central venous catheters have been inserted to enhance venous access for regular factor concentrate infusion in 45 patients with hemophilia ranging in age from 8 months to 19.5 years (median 7.4 years); 37 patients had factor VIII deficiency and 8 factor IX deficiency. Hemorrhagic complications of catheter placement were infrequent and minor. In the 41 patients having one or more IVADs in place for a median of 31 months, only six episodes of bacteremia occurred in 5 patients during 44,070 days of follow-up. The overall rate of bacteremia complicating IVADs in these patients was 0.14 episodes per 1000 catheter days. Other catheter-related complications were uncommon. Catheters are still in place in 33 patients for a median of 32 months. CONCLUSION: The low risk of infection and other complications associated with the use of IVADs makes the use of these devices attractive in the treatment of patients with hemophilia who require frequent venous access for factor concentrate infusions.

Anti-Bacterial Agents↗
PubMed1998

Contrast venography in young haemophiliacs with implantable central venous access devices.

To assess the risk of deep vein thrombosis in haemophiliacs with long-term central venous catheters, we studied haemophiliacs followed at our centre with implantable venous access devices (ports) in place for > 6 months. Medical records were reviewed for a history of catheter-related complications. Each patient was examined for physical stigmata of thrombosis. Patency of the vessels was evaluated by contrast venography. Of 21 males with ports, 19 had factor VIII deficiency and two factor IX deficiency. Nineteen ports were evaluable (i.e. were in place for > 6 months). Seventeen patients have their original ports in place; two ports were replaced for mechanical dysfunction (1) and recurrent infection (1). Difficulty withdrawing or infusing occurred with three ports, two of which were cleared with urokinase. Physical examination was normal on all 19 patients. Venograms were performed in 13 of 19 patients. Parents of the remaining six patients refused venography because of the need for peripheral venipuncture. One patient had a small nonocclusive thrombus on the same side as his functioning catheter, and another had minimal narrowing of the subclavian vein at the site of a prior catheter. The overall prevalence of clinically relevant upper venous system thrombosis identifiable by contrast venography was zero (95% CI, 0-23%). We conclude that haemophiliacs do not have as high a risk of thrombosis as other populations of patients with central venous catheters. The theoretical risk of thrombosis should not preclude use of central venous catheters in patients with haemophilia.

Adolescent↗
PubMed1997

Radiation-induced apoptosis in microvascular endothelial cells.

The response of the microvasculature to ionizing radiation is thought to be an important factor in the overall response of both normal tissues and tumours. It has recently been reported that basic fibroblast growth factor (bFGF), a potent mitogen for endothelial cells, protects large vessel endothelial cells from radiation-induced apoptosis in vitro. Microvessel cells are phenotypically distinct from large vessel cells. We studied the apoptotic response of confluent monolayers of capillary endothelial cells (ECs) to ionizing radiation and bFGF. Apoptosis was assessed by identifying changes in nuclear morphology, recording cell detachment rates and by detecting internucleosomal DNA fragmentation. Withdrawal of bFGF alone induces apoptosis in these monolayers. The magnitude of this apoptotic response depends upon the duration of bFGF withdrawal. Irradiation (2-10 Gy) induces apoptosis in a dose-dependent manner. Radiation-induced apoptosis occurs in a discrete wave 6-10 h after irradiation, and radiation-induced apoptosis is enhanced in cultures that are simultaneously deprived of bFGF. For example, 6 h after 10 Gy, 44.3% (s.e. 6.3%) of cells in the monolayer simultaneously deprived of bFGF exhibit apoptotic morphology compared with 19.8% (s.e. 3.8%) in the presence of bFGF. These studies show that either bFGF withdrawal or ionizing radiation can induce apoptosis in confluent monolayers of capillary endothelial cells and that radiation-induced apoptosis can be modified by the presence of bFGF.

Animals↗
PubMed1996

Current controversies in the management of idiopathic thrombocytopenic purpura during childhood.

Both acute and chronic ITP in children are generally benign conditions. Few patients develop serious complications or long-term sequelae. Therefore, most patients require little or no specific therapy. IVIG or high-dose steroids may benefit some patients who have evidence of clinical bleeding, and splenectomy may be of value in patients with chronic ITP whose lives are altered by low platelet counts or bleeding. It is difficult to predict which patients are at risk for the development of ICH, and severe hemorrhage is not always curtailed by prior or concomitant therapy. The decision to treat a child with ITP should be based on the entire clinical picture rather than on the platelet count alone.

Adolescent↗
PubMed1996

Tempol prevents impairment of the endothelial cell wound healing response caused by ionising radiation.

It is known that radiation therapy results in some form of damage to the microcirculation. In support of this view, we found that capillary endothelial cells (EC) treated with X-rays (8 Gy) were defective in their ability to recover a denuded area. A scrape wound of 2 mm width was produced in monolayers 30 min after X-ray or sham treatment. After 48 h, the number of cells migrating into each of five successive 125 microns zones from both sides of the original wound were determined. Greater numbers of sham-treated EC entered zones 3 and 4, compared with irradiated cultures, and only sham-treated EC entered the most distant zone 5. We examined actin fibre orientation within migrating irradiated and sham-treated EC using 2-(D-2-aminobutanoic acid)-7-(N6-((((3,6-bis(dimethylamino)xanthylium-9-yl) carboxyphenyl) amino)thioxomethyl)-L-lysine), chloride (NBD)-phalloidin, immunofluorescent microscopy and computer image analysis. After 48 h, sham-treated, but not irradiated EC, contained actin which was orientated perpendicular to the original wound edge. After 6-9 days, only sham-treated EC closed the wounds. Tempol (4 hydroxy-2,2,6,6-tetra methylpiperidine-1-oxyl)(0.5 or 2 mM)), included in the media during irradiation, prevented this wound healing delay, when measured within the first 24 h. In conclusion, radiation treatment of capillary EC results in a wound healing defect. This defect appears to be related to the EC's inability to realign actin. Tempol protects EC from exhibiting a wound healing delay.

Animals↗
PubMed1995

Basic fibroblast growth factor increases nitric oxide synthase production in bovine endothelial cells.

Basic fibroblast growth factor (bFGF) and nitric oxide (NO) are expressed by endothelial cells (EC) and are involved in regulation of endothelial functions. In vivo, bFGF has a hypotensive effect which is mediated, in part, through activation of nitric oxide synthase (NOS) and the subsequent generation of NO. Thus we hypothesized that regulation of NOS in EC might be modulated by bFGF. bFGF treatment of EC in vitro resulted in increased NADPH diaphorase staining, a histochemical marker associated with the presence of NOS. Using cGMP generation in a reporter cell as a bioassay for NO release, we demonstrated that bFGF treatment of EC leads to increased production of biologically active NO. Furthermore, bFGF treatment of EC resulted in an increase in cellular content of the endothelial form of NOS as shown by Western blot analysis. Finally, Northern blot analysis was used to demonstrate that message levels of the constitutive, calcium-dependent, endothelial form of NOS is increased in EC by treatment with bFGF in vitro. These results suggest that bFGF has potential to regulate vascular tone through the modulation of levels of endothelial NOS.

Animals↗
PubMed1994

Novel concepts in modification of radiation sensitivity.

PURPOSE: To determine whether biological effects of radiation, such as apoptosis, that differ from classical clonogenic cell killing, can be modified with agents that would not be expected to modify classical clonogenic cell killing. This would expand the range of potential modifiers of radiation therapy. METHODS AND MATERIALS: EL4 murine lymphoma cell apoptosis was determined by electrophoretic analysis of deoxyribonucleic acid (DNA) fragmentation. DNA was extracted 24 h after irradiation or addition of inducing agents. Modifiers of radiation-induced apoptosis were added immediately after irradiation. The effects of radiation on wounded endothelial monolayers were studied by scraping a line across the monolayer 30 min after irradiation. Cell detachment was used as an endpoint to determine the protective effect of prolonged exposure to retinol prior to irradiation. RESULTS: EL4 cell apoptosis can be induced by tert-butyl hydroperoxide or the glutathione oxidant SR-4077. Radiation-induced EL4 cell apoptosis can be inhibited with 3-aminobenzamide, an agent that sensitizes cells to classical clonogenic cell killing. Radiation-induced endothelial cell detachment from confluent monolayers can be modified by pretreatment with retinol. CONCLUSION: These results raise the possibility that radiation could induce apoptosis by an oxidative stress mechanism that is different from that involved in classical clonogenic cell killing. These and other recent findings encourage the notion that differential modification of classical clonogenic cell killing and other important endpoints of radiation action may be possible.

Animals↗