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| ID | Type | Description | Link |
|---|---|---|---|
| K01HL096434-02 | U.S. NIH Grant/Contract | View source | |
| 5R21HL096123-02 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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An open label, prospective, randomized cross-over phase II study in up to 60 sickle cell patients who are either homozygous for Hb S or have HbSB0 thalassemia. Initially, each patient will be treated for 6 weeks with placebo or a standard dose of propranolol (40 mg) every 12 hrs. This will be followed by a 2-week washout period after which, patients will receive the other treatment modality (placebo or propranolol).
We Hypothesize that propranolol administered in vivo on a daily basis for 6 weeks (1) will decrease baseline adhesion to endothelial cells and will substantially abrogate epinephrine-stimulated adhesion to endothelial cells, as measured in vitro; (2) will improve biomarkers of endothelial activation and dysfunction; and (3) can be safely used in patients with SCD. Thus, the use of propranolol in SCD may represent a safe and effective means of anti-adhesive therapy in SCD.
Study Objectives:
Primary Objective:
• To establish the safety and efficacy of long-term therapy with propranolol as an anti-adhesive therapy for SCD.
Secondary Objective:
• To evaluate changes in soluble markers of endothelial activation and dysfunction.
Correlative Science Objective:
• To determine whether response to propranolol therapy is associated with polymorphisms in genes encoding the proteins involved in the upregulation of Sickle Red Blood Cell (SS RBC) adhesion by epinephrine.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Propranolol | Experimental | Drug arm |
|
| Sugar pill | Placebo Comparator | Placebo arm |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Propranolol | Drug | Treatment will be with a standard propranolol dose of 40 mg every 12 hrs.Each patient will participate in 6 weeks of treatment with placebo or study drug (propranolol), followed by a 2-week wash-out period and then 6 weeks of treatment with the other modality (placebo or propranolol). |
| Measure | Description | Time Frame |
|---|---|---|
| SS RBC Adhesion (Epi -1d/cm2- vs. Sham) by Treatment | The stickiness of SS RBC will be evaluated by a well-established in vitro assay of adhesion of SS RBCs to cultured endothelial cells using a flow chamber. Overall change of adhesion from baseline to post intervention( Week 0 to 6 and week 8 to 14) in unstimulated cells (Sham treated) vs. Stimulated Red Blood Cells (Epi-treated) at 1 dyne/cm2 | Week 0 to 6 and week 8 to 14 |
| SS RBC Adhesion (Epi -2d/cm2- vs. Sham) by Treatment | The stickiness of SS RBC will be evaluated by a well-established in vitro assay of adhesion of SS RBCs to cultured endothelial cells using a flow chamber. Overall change of adhesion from baseline to post intervention( Week 0 to 6 and week 8 to 14) in unstimulated cells (Sham treated) vs. Stimulated Red Blood Cells (Epi-treated) at 2 dyne/cm2 | Week 0 to 6 and week 8 to 14 |
| SS RBC Adhesion (Epi -3d/cm2- vs. Sham) by Treatment | The stickiness of SS RBC will be evaluated by a well-established in vitro assay of adhesion of SS RBCs to cultured endothelial cells using a flow chamber. Overall change of adhesion from baseline to post intervention( Week 0 to 6 and week 8 to 14) in unstimulated cells (Sham treated) vs. Stimulated Red Blood Cells (Epi-treated) at 3 dyne/cm2 | Week 0 to 6 and week 8 to 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Change of Plasma Levels of sE-selectin | Biomarkers of Endothelial Activation and Dysfunction: Overall change of Plasma levels of sE-selectin measured in triplicate on plasma samples using commercially available ELISA kits from baseline to post intervention ( Week 0 to 6 and week 8 to 14). | Week 0 to 6 and week 8 to 14 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15308566 | Background | Zennadi R, Hines PC, De Castro LM, Cartron JP, Parise LV, Telen MJ. Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-alphavbeta3 interactions. Blood. 2004 Dec 1;104(12):3774-81. doi: 10.1182/blood-2004-01-0042. Epub 2004 Aug 12. | |
| 17609430 | Background | Zennadi R, Moeller BJ, Whalen EJ, Batchvarova M, Xu K, Shan S, Delahunty M, Dewhirst MW, Telen MJ. Epinephrine-induced activation of LW-mediated sickle cell adhesion and vaso-occlusion in vivo. Blood. 2007 Oct 1;110(7):2708-17. doi: 10.1182/blood-2006-11-056101. Epub 2007 Jul 3. |
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Eighty-four patients were approached for the study, of those 28 declined to participate, 14 remained undecided. Forty-two patients consented. Thirthy-one of those consenting were enrolled and 27 randomized to the study.
Subjects were recruited from the Duke adult sickle cell clinic. Those that consented underwent a screening visit to determine eligibility. If eligible they were enrolled on the study and received study drug within 30 days of screening
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| ID | Title | Description |
|---|---|---|
| FG000 | Propranolol-first | Cross-over study comprising treatment with propranolol for 6 weeks with a standard dose of 40 mg every 12 hrs, followed by a 2 weeks period washout, then similar treatment period with placebo followed by another 2 weeks washout period |
| FG001 | Placebo-first | Cross-over study comprising treatment with placebo for 6 weeks, followed by a 2 weeks period washout, then similar treatment period with propranolol with a standard dose of 40 mg every 12 hrs., followed by another 2 weeks washout period. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention |
| |||||||||||||
| Washout |
| |||||||||||||
| Second Intervention |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Propranolol-first | Cross-over study comprising treatment with propranolol for 6 weeks with a standard dose of 40 mg every 12 hrs, followed by a 2 weeks period washout, then similar treatment period with placebo followed by another 2 weeks washout period |
| BG001 | Placebo-first |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | SS RBC Adhesion (Epi -1d/cm2- vs. Sham) by Treatment | The stickiness of SS RBC will be evaluated by a well-established in vitro assay of adhesion of SS RBCs to cultured endothelial cells using a flow chamber. Overall change of adhesion from baseline to post intervention( Week 0 to 6 and week 8 to 14) in unstimulated cells (Sham treated) vs. Stimulated Red Blood Cells (Epi-treated) at 1 dyne/cm2 | Posted | Mean | Standard Deviation | Percentage of total RBC | Week 0 to 6 and week 8 to 14 |
|
Not provided
All patients who were enrolled and had at least one baseline visit are included in the "at risk" category.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Propranolol | Propranolol: Treatment will be with a standard propranolol dose of 40 mg every 12 hrs.Each patient will participate in 6 weeks of treatment with placebo or study drug (propranolol), followed by a 2-week wash-out period and then 6 weeks of treatment with the other modality (placebo or propranolol). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vaso-occlusive crisis resulting in hospitalization | Musculoskeletal and connective tissue disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphadenopathy | Blood and lymphatic system disorders |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Laura De Castro, MD, MHSc | Duke University Medical Center | (412) 623-7026 | laura.decastro@dm.duke.edu |
Not provided
| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| D000267 | Tissue Adhesions |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
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| ID | Term |
|---|---|
| D011433 | Propranolol |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
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|
| Placebo | Drug | Treatment will be with a standard propranolol dose of 40 mg every 12 hrs.Each patient will participate in 6 weeks of treatment with placebo or study drug (propranolol), followed by a 2-week wash-out period and then 6 weeks of treatment with the other modality (placebo or propranolol). |
|
| Overall Change of Plasma Levels of sP-selectin |
Biomarkers of Endothelial Activation and Dysfunction: Overall change of Plasma levels of sP-selectin measured in triplicate on plasma samples using commercially available ELISA kits from baseline to post intervention ( Week 0 to 6 and weeks 8 to 14). |
| Week 0 to 6 and week 8 to 14 |
| Overall Change of Plasma Levels of sICAM-1 | Biomarkers of Endothelial Activation and Dysfunction: Overall change of Plasma levels of sICAM-1 measured in triplicate on plasma samples using commercially available ELISA kits from baseline to post intervention ( Week 0 to 6 and week 8 to 14) | Week 0 to 6 and week 8 to 14 |
| Overall Change of Plasma Levels of sVCAM-1 | Biomarkers of Endothelial Activation and Dysfunction: Overall change of Plasma levels of sVCAM-1 measured in triplicate on plasma samples using commercially available ELISA kits from baseline to post intervention ( Week 0 to 6 or week 8 to 14) | Week 0 to 6 and week 8 to 14 |
| Overall Change of Hemoglobin (Hgb) Levels | Overall change of Hemoglobin (Hgb) levels from baseline to post intervention( Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated | Week 0 to 6 and week 8 to 14 |
| Overall Change of Hematocrit (Hct) Levels | Overall change of Hematocrit (Hct) levels from baseline to post intervention( Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated | Week 0 to 6 and week 8 to 14 |
| Overall Change of Lactate Dehydrogenase (LDH) Levels | Overall change of LDH levels from baseline to post intervention( Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated | Week 0 to 6 and week 8 to 14 |
| Overall Change of Oxygen Saturation (02Sat) Levels | Overall change of Oxygen Saturation (02Sat) levels from baseline to post intervention( Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated | Week 0 to 6 and week 8 to 14 |
| Overall Change of Systolic Blood Pressure Levels | Overall change of Systolic Blood Pressure levels from baseline to post intervention (Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated | Week 0 to 6 and week 8 to 14 |
| Overall Change of Diastolic Blood Pressure Levels | Overall change of Diastolic Blood Pressure levels from baseline to post intervention (Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated | Week 0 to 6 and week 8 to 14 |
| 18664622 | Background | Zennadi R, Chien A, Xu K, Batchvarova M, Telen MJ. Sickle red cells induce adhesion of lymphocytes and monocytes to endothelium. Blood. 2008 Oct 15;112(8):3474-83. doi: 10.1182/blood-2008-01-134346. Epub 2008 Jul 29. |
| 18324973 | Background | Eyler CE, Jackson T, Elliott LE, De Castro LM, Jonassaint J, Ashley-Koch A, Telen MJ. beta(2)-Adrenergic receptor and adenylate cyclase gene polymorphisms affect sickle red cell adhesion. Br J Haematol. 2008 Apr;141(1):105-8. doi: 10.1111/j.1365-2141.2008.07008.x. |
| 23253664 | Background | De Castro LM, Zennadi R, Jonassaint JC, Batchvarova M, Telen MJ. Effect of propranolol as antiadhesive therapy in sickle cell disease. Clin Transl Sci. 2012 Dec;5(6):437-44. doi: 10.1111/cts.12005. Epub 2012 Oct 17. |
| NOT COMPLETED |
|
| NOT COMPLETED |
|
Cross-over study comprising treatment with placebo for 6 weeks, followed by a 2 weeks period washout, then similar treatment period with propranolol with a standard dose of 40 mg every 12 hrs., followed by another 2 weeks washout period |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | Overall Change of Plasma Levels of sE-selectin | Biomarkers of Endothelial Activation and Dysfunction: Overall change of Plasma levels of sE-selectin measured in triplicate on plasma samples using commercially available ELISA kits from baseline to post intervention ( Week 0 to 6 and week 8 to 14). | Posted | Mean | Standard Deviation | ng/ml | Week 0 to 6 and week 8 to 14 |
|
|
|
| Primary | SS RBC Adhesion (Epi -2d/cm2- vs. Sham) by Treatment | The stickiness of SS RBC will be evaluated by a well-established in vitro assay of adhesion of SS RBCs to cultured endothelial cells using a flow chamber. Overall change of adhesion from baseline to post intervention( Week 0 to 6 and week 8 to 14) in unstimulated cells (Sham treated) vs. Stimulated Red Blood Cells (Epi-treated) at 2 dyne/cm2 | Posted | Mean | Standard Deviation | Percentage of total RBC | Week 0 to 6 and week 8 to 14 |
|
|
|
| Primary | SS RBC Adhesion (Epi -3d/cm2- vs. Sham) by Treatment | The stickiness of SS RBC will be evaluated by a well-established in vitro assay of adhesion of SS RBCs to cultured endothelial cells using a flow chamber. Overall change of adhesion from baseline to post intervention( Week 0 to 6 and week 8 to 14) in unstimulated cells (Sham treated) vs. Stimulated Red Blood Cells (Epi-treated) at 3 dyne/cm2 | Posted | Mean | Standard Deviation | Percentage of total RBC | Week 0 to 6 and week 8 to 14 |
|
|
|
| Secondary | Overall Change of Plasma Levels of sP-selectin | Biomarkers of Endothelial Activation and Dysfunction: Overall change of Plasma levels of sP-selectin measured in triplicate on plasma samples using commercially available ELISA kits from baseline to post intervention ( Week 0 to 6 and weeks 8 to 14). | Posted | Mean | Standard Deviation | ng/ml | Week 0 to 6 and week 8 to 14 |
|
|
|
| Secondary | Overall Change of Plasma Levels of sICAM-1 | Biomarkers of Endothelial Activation and Dysfunction: Overall change of Plasma levels of sICAM-1 measured in triplicate on plasma samples using commercially available ELISA kits from baseline to post intervention ( Week 0 to 6 and week 8 to 14) | Posted | Mean | Standard Deviation | ng/ml | Week 0 to 6 and week 8 to 14 |
|
|
|
| Secondary | Overall Change of Plasma Levels of sVCAM-1 | Biomarkers of Endothelial Activation and Dysfunction: Overall change of Plasma levels of sVCAM-1 measured in triplicate on plasma samples using commercially available ELISA kits from baseline to post intervention ( Week 0 to 6 or week 8 to 14) | Posted | Mean | Standard Deviation | ng/ml | Week 0 to 6 and week 8 to 14 |
|
|
|
| Secondary | Overall Change of Hemoglobin (Hgb) Levels | Overall change of Hemoglobin (Hgb) levels from baseline to post intervention( Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated | Posted | Median | Inter-Quartile Range | gm/dL | Week 0 to 6 and week 8 to 14 |
|
|
|
| Secondary | Overall Change of Hematocrit (Hct) Levels | Overall change of Hematocrit (Hct) levels from baseline to post intervention( Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated | Posted | Median | Inter-Quartile Range | percentage of red blood cells | Week 0 to 6 and week 8 to 14 |
|
|
|
| Secondary | Overall Change of Lactate Dehydrogenase (LDH) Levels | Overall change of LDH levels from baseline to post intervention( Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated | Posted | Median | Inter-Quartile Range | IU/L | Week 0 to 6 and week 8 to 14 |
|
|
|
| Secondary | Overall Change of Oxygen Saturation (02Sat) Levels | Overall change of Oxygen Saturation (02Sat) levels from baseline to post intervention( Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated | Posted | Median | Inter-Quartile Range | percentage of oxygen saturation | Week 0 to 6 and week 8 to 14 |
|
|
|
| Secondary | Overall Change of Systolic Blood Pressure Levels | Overall change of Systolic Blood Pressure levels from baseline to post intervention (Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated | Posted | Median | Inter-Quartile Range | mmHg | Week 0 to 6 and week 8 to 14 |
|
|
|
| Secondary | Overall Change of Diastolic Blood Pressure Levels | Overall change of Diastolic Blood Pressure levels from baseline to post intervention (Week 0 to 6 and week 8 to 14) Placebo vs. Propranolol treated | Posted | Median | Inter-Quartile Range | mmHg | Week 0 to 6 and week 8 to 14 |
|
|
|
| 4 |
| 27 |
| 22 |
| 27 |
| EG001 | Placebo | Placebo: Treatment will be with a standard propranolol dose of 40 mg every 12 hrs.Each patient will participate in 6 weeks of treatment with placebo or study drug (propranolol), followed by a 2-week wash-out period and then 6 weeks of treatment with the other modality (placebo or propranolol). | 3 | 27 | 19 | 27 |
| Thrombocytopenia | Blood and lymphatic system disorders |
|
| Atrioventricular (AV) block | Cardiac disorders |
|
| Bradycardia | Cardiac disorders |
|
| Drop in Blood Pressure | Cardiac disorders |
|
| Bilateral conjunctivitis | Eye disorders |
|
| Abdominal Paiin | Gastrointestinal disorders |
|
| Abdominal cramping | Gastrointestinal disorders |
|
| Abdominal pain and bloating | Gastrointestinal disorders |
|
| Blood per rectum | Gastrointestinal disorders |
|
| Diarrhea | Gastrointestinal disorders |
|
| Diarrhea, intermittent | Gastrointestinal disorders |
|
| Nausea | Gastrointestinal disorders |
|
| Nausea and vomiting | Gastrointestinal disorders |
|
| Stomach ache | Gastrointestinal disorders |
|
| Extreme tiredness | General disorders |
|
| Fatigue | General disorders |
|
| Feeling of internal heat | General disorders |
|
| Increased Fatigue | General disorders |
|
| Shakes | General disorders |
|
| E Coli Bacteremia | Infections and infestations |
|
| Fever | Infections and infestations |
|
| MRSA Positive | Infections and infestations |
|
| Sinus Infection | Infections and infestations |
|
| Sore throat | Infections and infestations |
|
| Sensitivity to cold | Metabolism and nutrition disorders |
|
| Pain Crisis | Musculoskeletal and connective tissue disorders |
|
| Pain, Back | Musculoskeletal and connective tissue disorders |
|
| Pain, Bone | Musculoskeletal and connective tissue disorders |
|
| Pain, Increased knee pain | Musculoskeletal and connective tissue disorders |
|
| Pain, Jaw | Musculoskeletal and connective tissue disorders |
|
| Pain, Joint | Musculoskeletal and connective tissue disorders |
|
| Pain, Knee | Musculoskeletal and connective tissue disorders |
|
| Pain, Left chest wall | Musculoskeletal and connective tissue disorders |
|
| Pain, Leg | Musculoskeletal and connective tissue disorders |
|
| Pain, Musculoskeletal | Musculoskeletal and connective tissue disorders |
|
| Pain, back and chest | Musculoskeletal and connective tissue disorders |
|
| Toothache | Musculoskeletal and connective tissue disorders |
|
| Vaso-occlusive Crisis | Musculoskeletal and connective tissue disorders |
|
| Dizziness | Nervous system disorders |
|
| Headache | Nervous system disorders |
|
| Headache, extreme | Nervous system disorders |
|
| Worsening depression | Psychiatric disorders |
|
| Pylonephritis due to E. Coli | Renal and urinary disorders |
|
| Smelly urine and bladder spasms | Renal and urinary disorders |
|
| Delayed menstrual period | Reproductive system and breast disorders |
|
| Prolonged menstrual period | Reproductive system and breast disorders |
|
| Congestion, Upper Chest | Respiratory, thoracic and mediastinal disorders |
|
| Cough | Respiratory, thoracic and mediastinal disorders |
|
| Coughing, congestion | Respiratory, thoracic and mediastinal disorders |
|
| Hoarseness | Respiratory, thoracic and mediastinal disorders |
|
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders |
|
| Sneezing/Allergies | Respiratory, thoracic and mediastinal disorders |
|
| Rash | Skin and subcutaneous tissue disorders |
|
| Skin abrasions due to pruritus | Skin and subcutaneous tissue disorders |
|
| Thrush | Respiratory, thoracic and mediastinal disorders |
|
| Atypical mycoplasma pneumonia, Suspected | Infections and infestations |
|
| Fracture, left foot | Musculoskeletal and connective tissue disorders |
|
| Fatigue with chest tightness | Musculoskeletal and connective tissue disorders |
|
| Pain, Hip | Musculoskeletal and connective tissue disorders |
|
| Pain, Migrating | Musculoskeletal and connective tissue disorders |
|
| Pain episode | Musculoskeletal and connective tissue disorders |
|
| Pain, Right foot, plantar | Musculoskeletal and connective tissue disorders |
|
| Pain, Leg, sharp shooting | Musculoskeletal and connective tissue disorders |
|
| Pain, Shoulder/Chest | Musculoskeletal and connective tissue disorders |
|
| Weakness | Musculoskeletal and connective tissue disorders |
|
| Dizziness/Vertigo | Nervous system disorders |
|
| Headache, Intermittent | Nervous system disorders |
|
| Lightheadness | Nervous system disorders |
|
| Vertigo | Nervous system disorders |
|
| Cold symptoms | Respiratory, thoracic and mediastinal disorders |
|
| Shortness of breath on exertion | Respiratory, thoracic and mediastinal disorders |
|
| Sore throat, intermittent | Respiratory, thoracic and mediastinal disorders |
|
| Runny nose | Respiratory, thoracic and mediastinal disorders |
|
| Shortness of breath | Respiratory, thoracic and mediastinal disorders |
|
| sinus allergies | Respiratory, thoracic and mediastinal disorders |
|
| Congestion, Sinus | Respiratory, thoracic and mediastinal disorders |
|
| Sore throat, worsening | Respiratory, thoracic and mediastinal disorders |
|
| Skin abrasions due to pruritis | Skin and subcutaneous tissue disorders |
|
| ED Visit | General disorders |
|
Not provided
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| D006425 |
| Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D002921 | Cicatrix |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |