Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical, molecular, and genetic advances have revealed new pathophysiologic insights and treatments for the growing number of recognized hematologic and nonhematologic abnormalities in sickle cell disease. Treatment targets of cellular dehydration, sickle hemoglobin concentrations, endothelial dysfunction, and abnormal coagulation regulation have been validated as potential therapy. New uses for transfusion therapy hold the promise of decreased major symptoms of acute chest syndrome, stroke, and severe pain crises, but at the expense of increased risk for transfusion reactions, infections, and iron overload. Accumulated experience with autologous, chimeric, and stem cell bone marrow transplantation holds promise for a small percentage of patients with disease. Patient selection, suitable donors, and early mortality are still limiting factors. Genetic manipulation, which offers hope for ameliorating the disease in a larger percentage of patients, is progressing slowly. Combination and staged therapies will be developed and matched to the severity and progression of the patient's disease. Strategies for prevention of major organ damage to the brain, heart, lungs, and kidneys will be prospectively evaluated and refined.
 ...
PMID:Major changes in sickle cell disease. 1095 46

Augmentation of the fetal hemoglobin (HbF) levels is of therapeutic benefit in patients with sickle cell anemia. Hydroxyurea (HU), by increasing HbF, lowers rates of pain crisis, episodes of acute chest syndrome, and requirements for blood transfusions. For patients with no HbF elevation after HU treatment, augmentation of HbF levels by 5-aza-2'-deoxycytidine (5-aza-CdR, decitabine) could serve as an alternate mode of treatment. Eight adult patients participated in a dose-escalating phase I/II study with 5-aza-CdR at doses ranging from 0.15 to 0.30 mg/kg given 5 days a week for 2 weeks. HbF, F cell, F/F cell, gamma-globin synthesis ratio, complete blood count, and chemistry were measured. The average gamma-globin synthesis relative to non-alpha-globin synthesis prior to therapy was 3.19% +/- 1.43% and increased to 13.66% +/- 4.35% after treatment. HbF increased from 3.55% +/- 2.47% to 13.45% +/- 3.69%. F cells increased from 21% +/- 14.8% to 55% +/- 13.5% and HbF/F cell increased from 17% to 24%. In the HU nonresponders HbF levels increased from 2.28% +/- 1.61% to 2.6% +/- 2.15% on HU, whereas on 5-aza-CdR HbF increased to 12.70% +/- 1.81%. Total hemoglobin increased by 1 g/dL in 6 of 8 patients with only minor reversible toxicities, and all patients tolerated the drug. Maximum HbF was attained within 4 weeks of treatment and persisted for 2 weeks before falling below 90% of the maximum. Therefore 5-aza-CdR could be effective in increasing HbF in patients with sickle cell anemia who failed to increase HbF with HU. Demonstration of sustained F levels with additional treatment cycles without toxicity is currently being performed.
 ...
PMID:2-deoxy 5-azacytidine and fetal hemoglobin induction in sickle cell anemia. 1100 87

A subset of 299 patients with homozygous sickle cell anaemia, enrolled in the cohort of the French Study Group on sickle cell disease (SCD), was investigated in this study. The majority of patients were children (mean age 10.1 +/- 5.8 yr) of first generation immigrants from Western and Central Africa, the others originated from the French West Indies (20.2%). We report the frequency of the main clinical events (mean follow-up 4.2 +/- 2.2 yr). The prevalence of meningitis-septicaemia and osteomyelitis was, respectively, 11.4% and 12% acute chest syndrome was observed in 134 patients (44.8%). Twenty patients (6.7%) developed stroke with peak prevalence at 10-15 yr of age. One hundred and seventy-two patients (58%) suffered from one or more painful sickle cell crises, while the others (42.5%) never suffered from pain. The overall frequency of acute anaemic episodes was 50.5%, (acute aplastic anaemia 46%; acute splenic sequestration 26%). A group of 27 patients were asymptomatic (follow-up > 3 yr). Epistatic mechanisms influencing SCD were studied. Coinherited alpha-thalassemia strongly reduced the risk of stroke (p <0.001) and increased that of painful crises (p < 0.02). There was a low prevalence of Senegal and Bantu (CAR) betas-chromosomes in patients with meningitis (p <0.04) and osteomyelitis (p < 0.03). Prevalence of Senegal betas-chromosomes was lower in the asymptomatic group of 27 patients (p < 0.02). The patients come from a population of unmixed immigrants in whom the beta-globin gene haplotype strongly reflects the geographic origin and identifies subgroups with a homogenous genetic background. Thus the observed effects might result more from differences in as yet unidentified determinants in the genetic background than from the direct linkage with differences in the beta-globin gene locus.
 ...
PMID:Acute clinical events in 299 homozygous sickle cell patients living in France. French Study Group on Sickle Cell Disease. 1100 50

Treatment advances over the past 25 years have significantly decreased morbidity and mortality in children with sickle cell disease. Aggressive management of fever, early diagnosis of acute chest syndrome, judicious use of transfusions and proper treatment of pain can improve quality of life and prognosis for these children. Prophylactic hydroxyurea therapy has been shown to reduce the incidence and severity of pain crises in adults with sickle cell disease and has been effective in limited studies conducted in children. Research into stem cell transplantation provides hope that a cure for sickle cell disease may be possible.
 ...
PMID:Sickle cell disease in childhood: Part II. Diagnosis and treatment of major complications and recent advances in treatment. 1101 59

Cholecystectomy is a common surgical procedure performed in patients with sickle cell disease (SCD). Postoperative complications, including acute painful vaso-occlusive crisis and acute chest syndrome, have been described frequently after either traditional or laparoscopic cholecystectomy (LC). It's still not clear if preoperative blood transfusion, hyperhydration, intraoperative body temperature conservation may reduce complications rate. The Authors reviewed the charts of seven patients with SCD operated on LC for symptomatic gallbladder lithiasis and describe their perioperative management. In 3 patients preoperative endoscopic removal of stones was achieved. Five patients with HB lower than 9 g/dl and/or HbS higher than 40% were transfused preoperatively and all the patients were hyperhydrated. Intraoperative monitoring was achieved for early recognition of ventilation to perfusion mismatch and acid-base balance or temperature modifications. The Authors reported only one case of postoperative lower extremities pain. This study suggests that LC is a safe procedure in SCD if appropriate monitoring and perioperative management are achieved.
 ...
PMID:Laparoscopic cholecystectomy in adult patients with sickle cell disease. 1127 37

Acute chest syndrome is a major cause of death and hospitalisation in children with sickle cell anaemia. It is often initiated by an infection, particularly pneumonia. Microbial agents previously not associated with acute chest syndrome are becoming increasingly important. Group A beta-haemolytic Streptococcus (GABHS) is thought to be an uncommon cause of pneumonia in children with sickle cell anaemia. We report a 15-year-old African-American girl who presented with an acute chest event characterised by fever, cough, chest pain, shortness of breath, right upper abdominal quadrant pain, jaundice and otitis media. Chest radiograph showed multi-lobar pneumonia with left pleural effusion. Group A beta-haemolytic Streptococcus was isolated from culture of pleural and middle ear fluids. She responded to therapy that included antibiotics, exchange blood transfusion, oxygen, thoracotomy chest tube drainage and decortication. In a child with sickle cell anaemia presenting with fever and an acute chest event, pneumonia should be considered and GABHS recognised as a possible aetiological agent. In addition, a chest X-ray should be obtained and antibiotics against agents causing community-acquired pneumonia instituted.
 ...
PMID:Group A beta-haemolytic streptococcal acute chest event in a child with sickle cell anaemia. 1147 Dec 64

Painful episodes are the most frequent complaints of patients with sickle cell disease. The Emergency Department (ED) has provided management for acute events using the usual triage format for emergencies. A prospective study evaluated the role of the ED in the care of adults with sickle cell disease (SCD). The protocol, thus, addressed issues of acute events related to SCD and provided better care for patients with SCD in the ED. Approximately 37% of ED visits were for painful events. An inciting cause was identified in 35% of painful events and 75% of these required admission to the hospital. A 15-year follow-up prospectively showed similar results and that uncomplicated pain crisis can be treated with ED protocols. Outpatient clinics and urgent centers could reduce these visits. Absolute indications for admission include sepsis, fever >102 degreeF, white cell counts >20 000, worsening anemia, hypoxemia, acute chest syndrome and new CNS events. Patient database in the ED must be revised annually to avoid extensive workup in the ED and a complete history/physical examination, and a CBC could be sufficient for triage in an uncomplicated pain crisis. An acceptable protocol for care should be available at all EDs and a registry and information system for SCD will discourage overutilization of investigational tests and visits to multiple EDs.
 ...
PMID:Evaluation and Management of Sickle Cell Disease in the Emergency Department (An 18-year Experience): 1974--1992. 1183 5

Splenectomy is frequently required in children with various hematologic disorders. The reported advantages of laparoscopic splenectomy (LS) include less pain, shorter hospital stay, and improved cosmesis. This report evaluates the outcome of children undergoing LS at a single children's facility. One hundred twelve children underwent LS by the lateral approach between August 1995 and February 2001. Indications for LS were hereditary spherocytosis in 58, idiopathic thrombocytopenic purpura in 21, sickle cell disease in 19, and other conditions in 14. LS alone was completed in 89 children and LS and cholecystectomy (LSC) in 20. Three required conversion to open splenectomy. Accessory spleens were identified in 19. Complications included ileus (four), acute chest syndrome (four), bleeding (two), pneumonia (one), and diaphragm perforation (one). There was no mortality. An accessory spleen was missed in one child with recurrent anemia. Average operative time for LS was 106 minutes and for LSC 135 minutes. Operative time for LS decreased with experience but the difference was not significant. Average length of stay was 1.51 days (range 1-11) and was longer in sickle cell disease (2.47 days) versus hereditary spherocytosis (1.29 days) and idiopathic thrombocytopenic purpura (1.16 days). We conclude that LS is safe and effective in children with hematologic disorders and is associated with minimal morbidity, zero mortality, and a short length of stay.
 ...
PMID:Laparoscopic splenectomy has become the gold standard in children. 1189 57

The phenotypic expression of sickle cell anaemia varies greatly among patients and longitudinally in the same patient. It influences all aspects of the life of affected individuals including social interactions, intimate relationships, family relations, peer interactions, education, employment, spirituality and religiosity. The clinical manifestations of sickle cell anaemia are protean and fall into three major categories: anaemia and its sequelae;pain and related issues; andorgan failure including infection. Recent studies on the pathogenesis of sickle cell anaemia have centred on the sequence of events that occur between polymerisation of deoxy haemoglobin (Hb) S and vaso-occlusion. Cellular dehydration, inflammatory response and reperfusion injury seem to be important pathophysiological mechanisms. Management of sickle cell anaemia continues to be primarily palliative in nature, including supportive, symptomatic and preventative approaches to therapy. Empowerment and education are the major aspects of supportive care. Symptomatic management includes pain management, blood transfusion and treatment of organ failure. Pain managment should follow certain priniciples that include assessment, individualisation of therapy and proper utilisation of opioid and nonopioid analgesics in order to acheive adequate pain relief. Blood selected for transfusion should be leuko-reduced and phenotypically matched for the C, E and Kell antigens. Exchange transfusion is indicated in patients who are transfused chronically in order to prevent or delay the onset of iron-overload. Acute chest syndrome is the most common form of organ failure and its management should be agressive, including adequate ventilation, multiple antibacterials and simple or exchange blood transfusion depending on its severity. Preventitive therapy includes prophylactic penicillin in infants and children, blood transfusion (preferably exchange transfusion) in patients with stroke, and hydroxyurea in patients with frequent acute painful episodes. Bone marrow and cord blood transplantation have been successful modalities of curative therapy in selected children with sickle cell anaemia. Newer approaches to preventative therapy include cellular rehydration with agents that inhibit the Gardos channel or the KCl co-transport channel. Curative gene therapy continues to be investigational at the level of the test tube and transgenic mouse models.
 ...
PMID:Sickle cell anaemia: progress in pathogenesis and treatment. 1201 77

Although the manifestations of sickle cell disease (SCD) do not typically necessitate critical care management, several life-threatening complications may require admission to the pediatric intensive care unit. Children with SCD are at risk for serious complications such as vaso-occlusive pain crises, cerebral vascular accidents, acute chest syndrome, severe anemia related to aplastic and splenic sequestration crises, infection, and multiorgan failure. Despite years of study, little progress has been made in understanding the pathophysiology of SCD. For this reason, management has been primarily focused on treating the negative sequelae of the disease. However, exciting ongoing research has led to great improvements not only in the understanding of the disease, but also in what was once considered routine therapy for SCD. Research on the use of modalities such as inhaled nitric oxide, L-arginine therapy, and transcranial Doppler ultrasound, and the development of blood transfusion programs are making strides in reducing morbidity and mortality, and in improving the quality of life for children with SCD. Perhaps most exciting are the advances in bone marrow and stem cell transplantation, which offer hope of an eventual cure for this debilitating and deadly disease. Advanced practice nurses play a pivotal role in coordinating care for these critically ill children. Knowledge of both current and investigational therapies allows the advanced practice nurse to provide comprehensive, state-of-the-art care to children with life-threatening complications of SCD.
 ...
PMID:Sickle cell anemia in the pediatric intensive care unit: novel approaches for managing life-threatening complications. 1201 90


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>