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Biomedical subjects

C P Alfrey

Publications and source records attributed to C P Alfrey.

At least 19 recordsLinked to original sources
PubMed1997

Neocytolysis: physiological down-regulator of red-cell mass.

It is usually considered that red-cell mass is controlled by erythropoietin-driven bone marrow red-cell production, and no physiological mechanisms can shorten survival of circulating red cells. In adapting to acute plethora in microgravity, astronauts' red-cell mass falls too rapidly to be explained by diminished red-cell production. Ferrokinetics show no early decline in erythropolesis, but red cells radiolabelled 12 days before launch survive normally. Selective destruction of the youngest circulating red cells-a process we call neocytolysis-is the only plausible explanation. A fall in erythropoietin below a threshold is likely to initiate neocytolysis, probably by influencing surface-adhesion molecules. Recognition of neocytolysis will require re-examination of the pathophysiology and treatment of several blood disorders, including the anaemia of renal disease.

Adaptation, Physiological↗
PubMed1996

Destruction of newly released red blood cells in space flight.

Space flight results in a rapid change in total blood volume, plasma volume, and red blood cell mass because the space to contain blood is decreased. The plasma volume and total blood volume decreases during the first hours in space and remain at a decreased level for the remainder of the flight. During the first several hours following return to earth, plasma volume and total blood volume increase to preflight levels. During the first few days in space recently produced red blood cells disappear from the blood resulting in a decrease in red blood cell mass of 10-15%. Red cells 12 d old or older survive normally and production of new cells continues at near preflight levels. After the first few days in space, the red cell mass is stable at the decreased level. Following return to earth the hemoglobin and red blood cell mass concentrations decrease reflecting the increase in plasma volume. The erythropoietin levels increase responding to "postflight anemia"; red cell production increases, and the red cell mass is restored to preflight levels after several weeks.

Adaptation, Physiological↗
PubMed1996

Regulation of body fluid compartments during short-term spaceflight.

The fluid and electrolyte regulation experiment with seven subjects was designed to describe body fluid, renal, and fluid regulatory hormone responses during the Spacelab Life Sciences-1 (9 days) and -2 (14 days) missions. Total body water did not change significantly. Plasma volume (PV; P < 0.05) and extracellular fluid volume (ECFV; P < 0.10) decreased 21 h after launch, remaining below preflight levels until after landing. Fluid intake decreased during weightlessness, and glomerular filtration rate (GFR) increased in the first 2 days and on day 8 (P < 0.05). Urinary antidiuretic hormone (ADH) excretion increased (P < 0.05) and fluid excretion decreased early in flight (P < 0.10). Plasma renin activity (PRA; P < 0.10) and aldosterone (P < 0.05) decreased in the first few hours after launch; PRA increased 1 wk later (P < 0.05). During flight, plasma atrial natriuretic peptide concentrations were consistently lower than preflight means, and urinary cortisol excretion was usually greater than preflight levels. Acceleration at launch and landing probably caused increases in ADH and cortisol excretion, and a shift of fluid from the extracellular to the intracellular compartment would account for reductions in ECFV. Increased permeability of capillary membranes may be the most important mechanism causing spaceflight-induced PV reduction, which is probably maintained by increased GFR and other mechanisms. If the Gauer-Henry reflex operates during spaceflight, it must be completed within the first 21 h of flight and be succeeded by establishment of a reduced PV set point.

Adult↗
PubMed1996

Control of red blood cell mass in spaceflight.

The effect of spaceflight on red blood cell mass (RBCM), plasma volume (PV), erythron iron turnover, serum erythropoietin, and red blood cell (RBC) production and survival and indexes were determined for six astronauts on two shuttle missions, 9 and 14 days in duration, respectively. PV decreased within the first day. RBCM decreased because of destruction of RBCs either newly released or scheduled to be released from the bone marrow. Older RBCs survived normally. On return to Earth, plasma volume increased, hemoglobin concentration and RBC count declined, and serum erythropoietin increased. We propose that entry into microgravity results in acute plethora as a result of a decrease in vascular space. PV decreases, causing an increase in hemoglobin concentration that effects a decrease in erythropoietin or other growth factors or cytokines. The RBCM decreases by destruction of recently formed RBCs to a level appropriate for the microgravity environment. Return to Earth results sequentially in acute hypovolemia as vascular space dependent on gravity is refilled, an increase in plasma volume, a decrease in hemoglobin concentration (anemia), and an increase in serum erythropoietin.

Adaptation, Physiological↗
PubMed1995

Decreased production of red blood cells in human subjects exposed to microgravity.

The total-body red blood cell mass (RBCM) decreases during the first few days of spaceflight; however, the pathophysiology of "spaceflight anemia" noted on return to earth is poorly understood. In studies before, during, and after a 9-day mission we determined the rates of removal and replacement of RBCs by using chromium 51. The rate and efficiency of RBC production were assessed with iron 59. Serial measurements were made of plasma volume (PV), RBCM, serum ferritin level, and erythropoietin level. PV decreased within hours, resulting in an increased total body hematocrit during the first few days of the mission. Serum erythropoietin level decreased within 24 hours and remained low. Circulating RBCs disappeared at a normal rate during flight, but few new cells replaced those destroyed, resulting in a decrease in RBCM of 11% during the mission. After 22 hours in space, intramedullary formation of cells continued at near preflight levels as measured by erythron iron turnover. The coexistence of new cell formation in the bone marrow and failure of cells to be released into the blood is consistent with ineffective erythropoiesis. Microgravity causes blood located in gravity-dependent spaces to shift to a central volume. We conclude that the initial adaptation is a reduction in PV resulting in plethora. Increase in total body hematocrit causes a decrease in erythropoietin production. RBCM decreases because RBCs destroyed at a normal rate are not replaced.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Volume↗
PubMed1988

Lymphocyte surface ferritin in malignant and inflammatory diseases.

We developed a lymphocyte ferritin antibody-binding test (LFABT) to measure lymphocyte surface ferritin (LSF) and used it in cases of malignant and other diseases associated with elevated serum ferritin. LSF was elevated in 33 of 83 patients with a variety of malignant neoplasms in all stages of disease. LSF was also elevated in 2 of 5 patients with infectious mononucleosis, but was normal in all 15 patients with rheumatoid arthritis, bacterial infections and hemochromatosis. LSF and serum ferritin levels do not correlate. These findings suggest the usefulness of LFABT as a diagnostic tool and demonstrate the biologic significance of LSF.

Antigen-Antibody Reactions↗
PubMed1987

Suppression of hemoglobin H in disorders of iron metabolism.

Disorders of iron metabolism affect the expression of hemoglobin H in hemoglobin H disease. Two cases of iron deficiency with reduced synthesis of hemoglobin H are described in the literature. We report two more cases, one with anemia of chronic disease and another with alcoholic sideroblastic anemia where the hemoglobin H was not detected at presentation and appeared after treatment of the underlying disorder. The pathogenesis of suppression of hemoglobin H is discussed.

Adolescent↗
PubMed1980

Effect of transfusion on hemoglobin flow and oxygen delivery in patients with sickle cell anemia--in vitro evaluation.

A method is given for the in vitro evaluation of transfusion therapy of patients with sickle cell anemia. Changes in volumetric flow rate, hemoglobin flow rate, and oxygen delivery at three values of PO2 (25, 40, and 80 mmHg) induced by transfusion of two units of AA blood in three patients are evaluated. The viscosity-shear rate data are obtained in a precision cone and plate viscometer with controlled environment. This data is then used to calculate flow rates in model tubes of varying diameters (50-500 microns). The increase in oxygenated hemoglobin flow rates at low oxygen tensions after transfusion can be striking-sometimes greater than a factor of two. A preliminary evaluation of the potential effect of auto-transfusion or androgen therapy on these flow rates is also discussed.

Anemia, Sickle Cell↗
PubMed1978

Serum ferritin assay.

Ferritin is an iron storage protein of high-molecular weight which is primarily present in the liver, spleen, and bone marrow. A very sensitive immunoradiometric assay has been developed which permits determination of serum concentrations in normal persons and in patients with a variety of different disorders. In normal subjects, the serum ferritin concentration correlates very well with total body iron stores as measured by phlebotomy. The serum ferritin concentration is reduced in patients with iron-deficient anemia and is significantly higher in patients who are anemic for other reasons. Subject areas discussed in this review include the details of the immunoradiometric procedure, the sensitivity and accuracy of the assay, factors influencing the assay, values characteristic of a variety of clinical disorders, and the utility of the assay in clinical medicine and public health.

Female↗
PubMed1978

Platelet lysis and aggregation in shear fields.

A rotational viscometer was used to study the effects of shear stress on platelets in human platelet-rich plasma (PRP). For 5-min exposure times, shear stresses above 160 dynes/cm2 induced platelet lysis (as determined by release of platelet lactic dehydrogenase). For 30-s exposure times, shear stresses greater than 600 dynes/cm2 were required to induce platelet lysis. The platelet counts of sheared PRP were decreased to as low as one-fifth the original count due largely to shear-induced aggregation. The count is a minimum at intermediate stress levels (200-400 dynes/cm2). Higher stresses induce disaggregation as well as lysis. The diminution in the counts was partially reversed in 2 h incubation after cessation of shearing. Experiments were carried out with three different viscometer configurations so that the shear stress and the solid surface area access could be varied independently. Surface access was not a significant variable in the conditions of the experiments. Thus aggregation and lysis may be induced by stress effects alone as well as by solid surface effects. The results also show that the response of platelets to shear stress is strongly dependent on exposure time. Platelets are much less resistant to shear stress than red cells for relatively long exposure times. However, the converse is true for very short exposure times.

Blood Platelets↗
PubMed1976

Erythrokinetics and androgens in bone marrow cancer.

Erythrokinetic studies were conducted in 60 patients with chronic anemia due to bone marrow involvement by cancer and other diseases. Fifty-seven percent had evidence of ineffective erythropoiesis contributing to the severity of their anemia. Enhanced bone marrow activity in the extremities was detected in 14% of patients. Maximal doses of several oral androgens were given to 31 patients for at least 3 months. Only 26% of the patients increased their red cell mass by at least 20%. All who benefitted had a minimum level of effective erythropoiesis and showed a decline in serum iron concentration at least 30 mug/100 ml after 1 month of treatment. Erythropoietin values were not helpful in identifying responding patients. These findings indicated the value of erythrokinetic studies in defining the bone marrow capacity of patients with cancer who are considered for androgen treatment trials.

Androgens↗
PubMed1976

Influence of cephalosporin antibiotics on blood coagulation and platelet function.

Administration of cephalothin to normal volunteers in maximal doses of 300 mg/kg per day resulted in a combined defect of platelet function and blood coagulation. No such abnormalities were evident after infusion of cefazolin or cephapirin at a maximal dosage of 200 mg/kg per day. The observed thrombocytopathy was similar to but less severe than that induced by carbenicillin or ticarcillin and was not reflected by a prolonged bleeding time test or impaired prothrombin consumption. Moreover, it was not a consistent finding in those persons receiving cephalothin. A separate defect involving blood coagulation appeared to result from delayed fibrinogen-fibrin polymerization and was evidenced by extended values of the activated partial thromboplastin and thrombin time tests. It remains uncertain whether the abnormalities described may constitute clinically important hemostatic disorders in patients with normal renal function receiving large doses of cephalosporin antibiotics.

Blood Coagulation↗