Please select the eligibility criteria that correspond to the clinical trial below.
Title: Adverse Effects of RBC Transfusions: A Unifying Hypothesis
Brief Summary: Transfusion of red blood cells is often used in critically ill patients with low red blood cell counts to prevent disease progression and death. Recent studies suggest that the use of "aged" versus "fresh" red blood cells are associated with worse clinical outcomes. There is evidence that red blood cells work with the cells lining our blood vessels to produce a variety of substances that normally cause arteries to relax and increase blood supply. Two of these substances are called nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). The investigators are trying to determine the nature of these substances in human beings when they are transfused "aged" versus "fresh" red blood cells. It is their thought that "aged" red blood cells have less of the substances (NO and EDHF) that naturally relax our arteries and further changes the blood supply. One way to determine this is to transfuse a subject's own "aged" and "fresh" red blood cells and inject substances such as L-NMMA (L-NG monomethyl arginine) and TEA (tetraethylammonium chloride), which block the production of NO and EDHF respectively, and then, study what happens to the blood flow.

There is evidence that red blood cells produce NO, which normally causes arteries to relax and increase blood supply. The investigators will try to determine the nature of NO in red blood cells and whether the amount of this substance is altered because of different blood processing and storage techniques. It is their thought that "aged" red blood cells have less NO that naturally relaxes our arteries and further changes the blood supply. This study is designed to determine the most ideal way of storing and processing blood.


Options:
A: Inclusion Criteria:

* Patients hospitalised in ICU with an anticipated ICU stay of at least 24 hours, in whom the decision has been made by medical staff to transfuse at least one RBC unit.

Exclusion Criteria:

* Age younger than 18
* Previous RBC transfusion during the current hospital admission (including transfusion in another hospital for transferred patients)
* Diagnosis of transplantation or hematologic diseases
* Pregnancy
* Cardiac surgery during the present hospital admission
* Expected to die imminently (\<24hrs)
* The treating physician believes it is not in the best interest of the patient to be randomised in this trial.
* Known objection to the administration of human blood products
* Participation in a competing study (see below)
B: Inclusion Criteria:

* Patients with sepsis, severe sepsis or septic shock who, according to clinical evaluation, need a hemotransfusion.

Exclusion Criteria:

* Patients under 18 years of age; Pregnancy; Coagulative disorders; Cardiogenic shock (Met\<4;)Acute massive bleeding (\>8 U)
C: Aim 1:

Inclusion Criteria:

* Healthy male or female volunteers (age 21-60 years)

Must meet guidelines for blood donors including:

* standard blood donor history questionnaire
* body weight of at least 110 lbs
* hemoglobin concentration of at least 12.5 gm/dL
* body temperature of no more than 99.5 oF
* pulse of 50-100 bpm
* blood pressure \< 180/100
* test negative for the standard battery of blood donor screening tests (anti-HIV, HIV RNA, anti-HCV, HCV RNA, HBsAg, anti-HBc, anti-HTLV-I/II, and WNV RNA)

Aim 1:

Exclusion Criteria:

* Failure to pass the blood donor history questionnaire
* Positive results on the standard battery of blood donor screening tests
* Failure to meet criteria for donation

Aim 2:

Inclusion Criteria:

* Healthy male or female volunteers (age 21-80 years)

Exclusion Criteria:

* Presence of intercurrent illness or other chronic diseases
* Renal failure (creatinine\>1.4 mg/dl)
* Pregnancy
* Allergies to aspirin
* Bleeding disorders
* Uncontrolled hypertension with BP \> 180 mmHg systolic and \> 120 mmHg diastolic
* Acute infection in previous 4 weeks
* History of substance abuse
* Liver failure (Liver enzymes \>2x normal)
* Inability to give informed consent
* Inability to return to Emory for follow-up
D: Inclusion Criteria:Children aged 6 - 59 months admitted at Acute care Unit - Mulago hospital with;

1. A positive B/S for malaria
2. Severe anemia ( Hb ≤ 5 g/dl) and
3. Lactic Acidosis (Blood lactate ≥ 5 mmol/l)
4. Written informed consent from the caretaker.

Exclusion Criteria:

1. Children undergoing transfusion with blood products other than packed cells.
2. Children with known or concurrent cardiac disease.

Answer: C