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Biomedical subjects

S A Landaw

Publications and source records attributed to S A Landaw.

At least 19 recordsLinked to original sources
PubMed1990

Polycythemia vera and other polycythemic states.

The diagnosis of polycythemia requires an accurate and independent assessment of both plasma volume and red blood cell mass. Patients with an increased red cell mass (absolute polycythemia) may be hypoxic or have an erythropoietin-secreting tumor or space-occupying lesion compressing the kidney. Those with a reduced plasma volume (relative polycythemia) most often are tobacco smokers, are taking diuretic or cardiac medications, or ingest increased quantities of caffeine-containing beverages. On the other hand, polycythemia vera is a systemic disease with multiple complications, which is best diagnosed through a complex of findings as outlined by the Polycythemia Vera Study Group.

Bone Marrow↗
PubMed1989

Targeting of heme oxygenase inhibitors to the spleen markedly increases their ability to diminish bilirubin production.

Incorporation of heme oxygenase inhibitors into phosphatidyl choline liposomes markedly enhanced localization of these agents within the spleen as compared with the localization observed following their administration in aqueous vehicle. The increased concentration of inhibitor within splenic microsomes led to a near complete and sustained blockade of heme oxygenase activity and thus to a marked diminution in biliary bilirubin output. These studies suggest that heme oxygenase inhibitors administered within liposomes may so effectively block bilirubin production in the human newborn that ancillary methods for treating this important clinical problem may be reduced to a minimum.

Animals↗
PubMed1988

Factors that accelerate or retard red blood cell senescence.

This article explores information concerning alterations in the time of age-related red blood cell (rbc) death (rbc senescence) in experimental animals and humans. Those factors that accelerate or retard the mean time for senescent death [the mean potential rbc life-span, (T)] are discussed; specifically excluded are conditions in which rbc survival is shortened due to an increase in the rate of age-independent [random hemolysis, (k)]rbc death. The factors prolonging senescence are reduction in metabolic rate through hibernation, reduced environmental temperature, hypophysectomy and thyroidectomy, and splenectomy. In general, these processes prolong rbc senescence by about 10%-15% in the models studied to date. The failure of splenectomy to prolong rbc senescence to any physiologically meaningful extent casts serious doubt on the concept that splenic processes are a major factor in the senescence process. Rbcs made under conditions of increased erythropoiesis and/or increased metabolic rate show acceleration of senescence. Thus, rbcs of animals treated with thyroxine show a 15% acceleration of senescence. "Stress reticulocytes" and normal full-term human newborn rbc may show up to 25% reduction in (T). The maximum acceleration seen to date is 50%-90%, as seen in the rbcs of the fetal and newborn rat. rbc senescence is not accelerated in rats with splenomegaly and increased rates of random hemolysis, again casting strong doubts on the spleen's ability to alter rbc senescence by progressively modifying the rbc during successive passages through that organ. It is postulated that rbc senescence is mainly a function of the red cell's initial endowment, particularly in the dynamic ability of that cell (and its membrane) to adapt to cumulative stresses that exist during its circulation through the body.

Animals↗
PubMed1987

Proof that Sn-protoporphyrin inhibits the enzymatic catabolism of heme in vivo. Suppression of 14CO generation from radiolabeled endogenous and exogenous heme sources.

Sn-protoporphyrin (SnPP) suppresses generation of 14CO from hepatic heme labeled with delta-aminolevulinic acid (5-[14C]ALA) or from infused [14C]hemin in rats. SnPP administered 1 h before administration of 5-[14C]ALA virtually abolished the peak output of 14CO occurring 2-3 h after injection of this heme precursor, and during the succeeding 12 h reduced 14CO excretion by approximately 61% compared with controls. When [14C]hemin was infused, SnPP diminished 14CO excretion by approximately 50%. These findings, derived from experiments using radiolabeled endogenous and exogenous heme sources, establish conclusively that the synthetic metalloporphyrin SnPP inhibits the oxidative degradation of heme in the intact animal.

Aminolevulinic Acid↗
PubMed1987

Thrombotic thrombocytopenic purpura: treatment with plasmapheresis.

Twenty-one episodes of thrombotic thrombocytopenic purpura (TTP) were treated with plasmapheresis. Adjunctive agents included corticosteroids, aspirin, dipyridamole, and vincristine. There were 17 patients; 12 were female. The median age was 41 years. Most patients presented with neurologic symptoms. Thrombocytopenia was profound with a mean initial platelet count of 14,900/mm3. The mean hematocrit on presentation was 26.7% and the mean LDH 1300 IU/L. Eighteen episodes responded completely following plasmapheresis/plasma exchange (86%). Response was prompt, the initial rise in platelet count occurred after a mean of four exchanges, and complete response (a platelet count over 150,000/mm3) was obtained after a mean of nine exchanges. Four of the episodes treated were relapses that occurred in three patients. All responders are alive with a median duration of follow-up of 20 months. The three patients who failed to respond have died. This report extends recent observations that the addition of plasmapheresis/plasma exchange to the therapy of TTP has significantly improved the outlook for patients with this disorder.

Adrenal Cortex Hormones↗
PubMed1985

Increased Heinz body formation and impaired erythrocyte pentose phosphate shunt function during pregnancy.

The erythrocytes of 90 pregnant women were evaluated for the presence of in vivo or in vitro oxidant damage. The reduced glutathione (P less than 0.005) and the membrane reduced sulfhydryl (P less than 0.001) concentrations were decreased in fresh erythrocytes. Following incubation with acetylphenylhydrazine, Heinz body formation was significantly increased (P less than 0.001). Both the increase in Heinz body formation and the reduction in membrane reduced sulfhydryl content correlated strongly with duration of pregnancy. Glucose consumption was significantly decreased before, but not after, new methylene blue stimulation. Pentose phosphate shunt activity was impaired both before (P less than 0.05) and after (P less than 0.001) stimulation. No changes were observed in pentose phosphate recycling. The only alteration observed in the activity of the enzymes of the pentose shunt was an elevation of 6-phosphogluconate dehydrogenase activity. Although the clinical significance of these findings remains to be determined, medications with an oxidant potential should be used judiciously during gestation.

Erythrocyte Aging↗
PubMed1985

Analysis of publication output of internal medicine faculty members.

The number of publications per year produced by a department of internal medicine faculty is analyzed. The output of the younger faculty members (40 years or less) averaged 1.4 publications a year, and the annual output of the older faculty (over 40 years) averaged 2.3 publications (p less than 0.05). The site of their primary clinical responsibilities did not significantly affect their publication productivity. In all subspecialty sections, the output of older faculty members correlated well with that of younger faculty members (p less than 0.005). The productivity of section chiefs correlated well with the productivity of younger faculty members in their respective sections (p less than 0.001). Younger faculty members who later entered private practice had a lower (p less than 0.02) publication output than those who left for another academic position. The output of faculty members is related to the age of the faculty members, overall sectional productivity, and productivity of the section chief.

Adult↗
PubMed1985

Bupivacaine alters red blood cell properties: a possible explanation for neonatal jaundice associated with maternal anesthesia.

Cord blood was incubated with lidocaine, mepivacaine, bupivacaine, or buffer and red blood cell filterability was determined. Only bupivacaine at either 1 or 2 micrograms/ml prolonged filterability by an average of 58 to 65% over red cells treated with buffer alone. Tritiated bupivacaine was bound to a greater extent to red cell ghosts from cord blood (24.6 +/- 5.8%) than to adult red cell ghosts (14.6 +/- 2.6%). Finally, we determined red cell survival in 13-day-old rats injected with bupivacaine or buffer. At 2 h after injection, buffer-treated animals had a red cell survival of 96.9 +/- 3.3%, whereas 2-h survival was reduced to 82.6 +/- 8.7% for the animals injected with bupivacaine. Our results suggest that the neonatal jaundice associated with maternal anesthesia, especially bupivacaine, may be related to the observations that these agents cross the placenta, bind to the red cell membrane and reduce its filterability, resulting in shortened red cell survival.

Adult↗
PubMed1979

Iron absorption in the thalassemia syndromes and its inhibition by tea.

To determine the hemoglobin concentration at which iron absorption is minimal, five subjects with thalassemia major and one with thalassemia intermedia underwent a series of iron-absorption studies. The effect of tea as an inhibitor of non-heme iron absorption was also tested. Iron absorption increased as the hemoglobin concentration decreased, although iron absorption was much higher at any given hemoglobin level in the subject with thalassemia intermedia. In the subjects with thalassemia major, iron absorption averaged 10 per cent at hemoglobin concentrations between 9 and 10 and 2.7 per cent between 11 and 13 g per deciliter. The percentage of iron absorbed could be accurately predicted from the nucleated red-cell count (r = 0.91, P less than 0.001). Tea produced a 41 to 95 per cent inhibition of iron absorption. Since patients with thalassemia intermedia may absorb a large percentage of dietary iron, inhibitors of iron absorption, such as tea, may be useful in their management.

Adolescent↗
PubMed1978

Smokers' polycythemia.

Twenty-two smokers with elevated hematocrits (mean, 54 per cent) had elevated blood carboxyhemoglobin (mean, 11.6 per cent; normal, less than 1 per cent) and a "left-shifted" oxygen-hemoglobin dissociation curve (mean P50, 21.6 +/- 2.3 [+/- S.D.] torr; normal, 26.7 +/- 1.1). Red-cell volume was increased in 14 of 18, and plasma volume reduced in 14 of 18. Fatigue and headache were common, and syncopal attacks occurred in four patients. Symptoms disappeared and the elevated red-cell volume decreased markedly in all five patients who were able to reduce severely their smoking habit; low plasma volume increased in three of four patients studied. We conclude that carbon monoxide exposure from cigar and cigarette smoke is a frequent cause of an elevated red-cell volume or a reduced plasma volume (or both). Measurement of carboxyhemoglobin should be a routine part of the evaluation of all polycythemic subjects.

Adult↗
PubMed1978

Alterations in erythrocyte survival parameters in rats after 19.5 days aboard Cosmos 782.

Rats were subjected to 19.5 d of weightless space flight aboard the Soviet biosatellite, Cosmos 782. Based on the output of 14CO, survival parameters of a cohort of erythrocytes labeled 15.5 d preflight were evaluated upon return from orbit. These were compared to vivarium control rats injected at the same time. Statistical evaluation indicates that all survival factors were altered by the space flight. The mean potential lifespan, which was 63.0 d in the control rats, was decreased to 59.0 d in the flight rats, and random hemolysis was increased three-fold in the flight rats. The measured size of the cohort was decreased, lending further support to the idea that hemolysis was accelerated during some portion of the flight. A number of factors that might be contributory to these changes are discussed, including forces associated with launch and reentry, atmospheric and environmental parameters, dietary factors, radiation, and weightlessness.

Animals↗
PubMed1977

Vitamin E and neonatal hemolysis.

A study was designed to determine if the presence of vitamin E deficiency during the first week of life played a contributory role in the shortened red cell life span observed in the premature infant. Carboxyhemoglobin values were used as an index of hemolysis. Ten infants received vitamin E administered intramuscularly in a total dose of 125 mg/kg during days 3 to 7 of life; ten infants served as controls. The mean percent carboxyhemoglobin level fell significantly from day 3 to day 8 in the treated group (1.08% to 0.78%) whereas the mean value remained unchanged at 0.96% in the control group. The administration of vitamin E appears to reduce but not eliminate the accelerated red cell destruction that characterizes the preterm infant. Pediatrics, 59:995-997, 1677, VITAMIN E, HEMOLYSIS, PREMATURE INFANT, CARBOXYHEMOGLOBIN.

Apgar Score↗
PubMed1977

Iron absorption from human milk, simulated human milk, and proprietary formulas.

Studies from our laboratory have shown that iron is better absorbed from human milk than from cow milk and that human milk can provide insufficient iron for infants during their first year. We compared iron availability from human milk with that from other formulas and determined the factors responsible for its superiority. Adults were fed 100 ml of human milk, simulated human milk, simulated human milk containing added lactoferrin, two commercial formulas containing iron, 12 mg/qt, and human milk that had been boiled. The simulated human milk resembled human milk in concentration of protein, fat, carbohydrate, iron, total minerals, calcium, and phosphorus. Iron 59 was added to each feeding and iron incorporation into RBCs was determined 14 days after each feeding. Percent iron absorption was highest from human milk and lowest from the commercial formulas. The simulated human milk supported a 9.0% absorption; addition of lactoferrin reduced this to 4.7%. Net iron absorption was 0.12 mg/liter from human milk and 0.40 and 0.37 mg/liter from the iron-enriched commercial formulas. Absorption of iron from boiled human milk was the same as from the unboiled milk. This study confirms the unique ability of human milk to promote iron absorption. Simple manipulation of the protein, fat, lactose, calcium, phosphorus, or lactoferrin content of proprietary milk did not reproduce the iron absorption demonstrated with human milk.

Adult↗
PubMed1977

Decreased surface charge and accelerated senescence of red blood cells following neuraminidase treatment.

Female LAF1 mice were given single or repeated injections of V. cholerae N'ase and the effects on circulating RBC surface charge and life span were determined. Intravenous injection of N'ase caused a rapid decrease in RBC surface charge of approximately 14 percent, and survival of such treated cells was reduced by approximately one fifth by virtue of an acceleration of senescence. When RBC's were treated in vitro with N'ase, a comparable (14 to 17 percent) reduction in surface charge was seen. Such cells, when injected into intact mice, showed a similar acceleration of senescence. When N'ase was injected intravenously into splenectomized mice, RBC survival was similar to that of controls. Intravenous injection of N'ase 1 hour before injection of labeled RBC's did not alter RBC survival nor did it accelerate the clearance of carbon particles by the RES. These results indicate that N'ase accelerates senescence in treated mouse erythrocytes by acting on the RBC's and not by activating the RES. Absence of this effect in splenectomized mice implicates the spleen as the sensor of the induced alterations in surface charge. These results and those recently reported for treated RBC's in the dog, rat, rabbit, and man suggest that at least a portion of the phenomenon of RBC senescence may be related to the loss of RBC surface charge.

Animals↗
PubMed1976

Acute leukemia in polycythemia vera.

Virtually every aspect concerning the occurrence of acute leukemia in polycythemia vera is controversial. However, a list of those factors believed to have importance in leukemogenesis in this disease includes: maleness, ethnic origin, the presence of myeloid metaplasia and/or early WBC precursors in the peripheral blood at the time of presentation, the influence of prolonged survival, and a possible dose-response relationship with 32P treatment. Many of the features of PV suggest that it is a malignant disease per se, with other factors (such as clones of cells, or altered host response) combining to increase the leukemogenic potential of the agents used to control the disease. It does appear that the incidence of AL in PV treated with 32P and/or x-ray is many times higher than that for PV treated with phlebotomy alone. However, overall survival for 32P-treated patients appears to be longer than that for phlebotomy treatment. Further, for both 32P and phlebotomy treatments, patients with AL do not die an an earlier age than do patients not developing this complication. Since the transformation of PV into AL has been described in more than 20 patients treated with phlebotomy alone, and in more than 30 patients treated with chemotherapy and phlebotomy, the question concerning the occurrence of AL in PV no longer appears to revolve around whether this is a function of the leukemogenicity of 32P or the effect of prolongation of survival. The occurrence of AL in multiple myeloma, lymphomas, other malignancies, and in nonmalignant diseases following treatment with myelosuppressive agents, forces one to consider the leukemogenic potential of any agent capable of suppressing the panmyelopathy of this disease, as well as the inherent tendency to AL of the "untreated" disease. Hopefully, the next decade will give us a more complete understanding of the complex interrelationships between PV, its treatment, and AL.

Female↗