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Biomedical subjects

S F Wallner

Publications and source records attributed to S F Wallner.

At least 19 recordsLinked to original sources
PubMed1987

The effect of topical agents on haematopoiesis following thermal injury: studies on an animal model.

Several investigators have described 'toxins' in the serum of burned patients that result in systemic alterations and in an overall breakdown of host defences. One of these toxins isolated from the burn eschar resulted in 80 per cent mortality when injected into non-burned mice. However, if the eschar was pretreated with cerium before isolating the toxin, the mortality in the recipients decreased. This experiment suggested that the cerium neutralized the toxin. We have partially isolated from the serum of burned patients and mice a substance that inhibits erythroid colony formation in vitro. To test if cerium neutralized this erythroid inhibitor, we applied cerium or silver nitrate to the eschar of a mouse model of thermal injury. We found that neither agent altered the level of inhibitor or any of the granulocyte or erythroid parameters measured.

Analysis of Variance↗
PubMed1987

The haematopoietic response to burning: studies in a splenectomized animal model.

Several haematopoietic changes occur following burning. These changes are important because they may effect a patient's ability to fight infection and to heal wounds. Studies of haematopoiesis in burned humans are difficult because of the complexity of these patients and because of the difficulty of collecting specimens. We therefore established a mouse model of these haematopoietic events; however, this model differed from the human situation as all three haematopoietic cell lines were being produced by the murine spleen. In this paper, we modified the model by removing the spleen and then repeating our previous studies. After splenectomy, granulocyte production, murine mortality and body weight did not change. Compared with the original model, the modified splenectomy model could not expand erythropoiesis. The result was greater anaemia. This model is, now, a closer simulation of the human situation and will prove useful in studies of haematopoiesis after thermal injury.

Animals↗
PubMed1986

Pancytopenia in propionic acidemia: hematologic evaluation and studies of hematopoiesis in vitro.

This study investigated the hematologic abnormalities of an infant with propionic acidemia and reversible pancytopenia. Light and electron microscopy of her bone marrow revealed severely disturbed cellular morphology with trilineage dysmyelopoiesis, hemophagocytosis, and numerous multinucleated histiocytes and megakaryocytes. The effects of her serum and of organic acids associated with propionic acidemia were studied on hematopoiesis in vitro. Mouse erythroid (CFU-E) and granulocyte-monocyte colonies (CFU-GM) were assayed by fibrin clot technique; human CFU-GM were grown in agar culture. The infant's serum reduced mouse CFU-E and CFU-GM by 43 and 32%, respectively, compared with normal human sera, but had no effect on human CFU-GM in our culture system. Buffered propionic acid caused concentration-dependent inhibition of mouse CFU-E and human CFU-GM over a range reported in sera of acutely ill infants with propionic acidemia. Neither cell viability nor subsequent colony formation was diminished by preincubation of bone marrow cells with propionic acid for 48 h. The three other organic acids studied, tiglic acid, 3-OH propionate, and glycine, did not inhibit growth of mouse CFU-E, CFU-GM, or human CFU-GM, and glycine significantly enhanced formation of the latter. Evaluation of the infant's hematologic abnormalities suggests that inhibition of bone marrow proliferation and maturation and, perhaps, shortened red blood cell survival were responsible for her pancytopenia. The studies performed in vitro implicate propionic acid in this hematopoietic dysfunction.

Amino Acid Metabolism, Inborn Errors↗
PubMed1986

The anemia of thermal injury: mechanism of inhibition of erythropoiesis.

The anemia of thermal injury is a multifactorial process and includes hemorrhage and hemolysis. Much evidence suggests that a reduced rate of erythropoiesis contributes to this anemia. Prior studies show that this anemia is temporally related to the appearance in burn patients sera of a substance(s) capable of inhibiting erythropoiesis in vitro. Four experiments were done to elucidate the mechanism of action of this inhibitor. In all experiments sera from burn patients previously shown to be inhibitory to erythropoiesis in vitro were studied. In the first, inhibitory sera were exposed to erythropoietin solutions without loss of erythropoietic activity. Second, mouse marrow cells were preincubated with serum without loss of their ability to form erythroid colonies. Third, the inhibitory effect could not be overcome with increasing amounts of erythropoietin. Finally, erythroid colony formation was effected only if the inhibitory serum was present during the first 8 to 12 hr of culture. The data suggest that the erythropoietic inhibitor in these sera acts directly on erythroid stem cells in vitro and not by inactivating or interference with erythropoietin.

Anemia↗
PubMed1985

The haematopoietic response to burning: an autopsy study.

Many haematopoietic changes follow severe burn injury. Abnormalities in the production and function of granulocytes have been reported, as have changes in peripheral blood platelet counts. Anaemia invariably occurs and has a multifactorial aetiology including haemorrhage and haemolysis. To study these changes further, haematopathological materials from 22 patients who had died of burning were compared with a control group of haematologically normal people who had died suddenly and a third group of patients who had died of sepsis. Granulocytes and megakaryocytes were increase in the marrow of burned patients while erythroid tissue was reduced compared with both control groups. There was no evidence of extramedullary haematopoiesis. This study provides morphological evidence that the rate of erythropoiesis is reduced post burn and suggests that this plays a role in the anaemia seen after burn injury.

Adult↗
PubMed1985

Granulocyte stem cells are decreased in humans with fatal burns.

The number of granulocytic stem cells (CFU-C) was measured in the peripheral blood of surviving and nonsurviving burned humans. It has been shown that the number of CFU-C in the peripheral blood of survivors increases over time and is elevated compared to the number found in normal humans. The number found in nonsurvivors, however, falls significantly in the later stages of burn injury, suggesting perhaps a defect in stem cell production and/or differentiation in patients with severe thermal injuries. The mechanism is unclear but its delineation may have an important bearing on understanding the nature of infectious complications following thermal injury.

Adult↗
PubMed1983

Cyclophosphamide, vincristine, lomustine, cisplatin, and doxorubicin in the treatment of non-small cell lung cancer.

Fifty-four patients (47 of whom were evaluable) with non-small cell lung cancer were treated with a five-drug regimen consisting of cyclophosphamide, vincristine, lomustine, cisplatin, and doxorubicin. Six complete and 16 partial responses were achieved, for an overall response rate of 47% (22 of 47 patients). Response by cell type was as follows: epidermoid carcinoma, 41% (seven of 17 patients); adenocarcinoma, 42% (eight of 19); and large cell carcinoma, 64% (seven of 11). Response in patients with limited disease was 48% (11 of 23 patients) and in patients with extensive disease, 46% (11 of 24). Previously untreated patients had response rates of 53%, versus 22% in those with prior therapy.

Adenocarcinoma↗
PubMed1982

The anemia of thermal injury: studies of erythropoiesis in vitro.

Anemia is invariably seen in patients who have been severely burned, and a number of factors have been implicated in its etiology. Prior studies have suggested that a depressed rate of erythropoiesis is involved. In order to study this, we evaluated the effect of serum from burned patients on red cell and white cell colony growth in vitro. We found that these sera were capable of inhibiting red cell, but not white cell, colony growth. Additional experiments indicated that this was related to the presence of some substance in the burned serum rather than the absence of a factor required for colony formation. Further studies, including review of clinical data, suggested that this effect was not due to topical medications nor to episodes of bacterial sepsis. Serial studies showed that inhibition was often not present in the immediate postburn period but developed gradually, reaching maximum intensity approximately 20 to 30 days following the burn and then returning toward normal as patients healed their injury. Our studies permit the hypothesis that inhibition of erythropoiesis plays a role in the pathogenesis of the anemia of thermal injury.

Adult↗
PubMed1981

Evidence that inhibition of erythropoiesis is important in the anemia of chronic renal failure.

Previous studies have documented that serum from patients with chronic renal failure is capable of inhibiting erythropoiesis in vitro. Few data, however, link this finding with the pathophysiology of the anemia of uremia. To study this, we correlated hematocrits from uremic patients with the degree to which serum from these patients inhibited erythropoiesis, using two different in vitro systems. We studied patients receiving hemodialysis and patients with varying degrees of uremia not receiving dialysis and did serial studies on patients in whom long-term hemodialysis was initiated. Study of patients with varying degrees of renal failure showed that levels of inhibitor developed and increased as renal failure worsened and the hematocrit level fell. Finally, we found a fall in inhibitor level in those patients who had an increase in hematocrit after long-term hemodialysis. We interpret these data as evidence that inhibition of erythropoiesis is involved in the anemia of chronic renal failure.

Anemia↗
PubMed1980

The anemia of chronic renal failure. Studies of iron transport in vitro.

Many studies indicate that serum from patients with CRF contains a material(s) which inhibits erythropoiesis in vitro. Little is known concerning the nature or mechanism of action of this inhibitory substance. Previous work has shown that 59Fe-heme synthesis rates of normal human or animal erythroblasts were suppressed in the presence of CRF serum. To further study the mechanism of inhibition of CRF serum, we evaluated the amount of iron present in various cellular fractions as a function of time in a fluid marrow culture system. Our data show that a reduction in heme synthesis occurs in plates prepared with uremic serum, which becomes most marked after 24 hr in culture. We were unable to find any significant difference in the amount of 59Fe attached to cellular membranes or in cell cytosol in cultures prepared with either normal or CRF serum. The data reject the hypothesis that the inhibitor somehow interferes with erythroblast membrane iron receptors or transport but suggest that it exerts its effort on heme synthesis.

Adult↗
PubMed1979

Macrocytic anemia, thrombocytosis and nonlobulated megakaryocytes: the 5q-syndrome, a distinct entity.

The clinical, hematologic and histologic characteristics of six patients with refractory anemia with deletion of the long arm of chromosome No. 5 are described. These patients had a distinct hematologic picture with macrocytic anemia of mild to moderate severity, normal to low leukocyte count and increased platelet count. The long arm of chromosome No. 5 was deleted in the majority of bone marrow metaphases. The main cause of anemia was underproduction with decreased erythroid precursors in the bone marrow and no increase in peripheral blood reticulocytes. Two of five patients responded transiently to the administration of androgens. In vitro evaluation of the bone marrow growth pattern in semisolid agar culture system was performed in three patients and was found to be normal and distinct from that in patients with preleukemia. In a follow up of up to five years, no patient had changed hematologically and in none had leukemia developed. The 5q-syndrome is a distinct hematologic entity and probably more common than hitherto realized. This diagnosis may have therapeutic and prognostic implications.

Adult↗
PubMed1978

Prognostic importance of pruritus in Hodgkin's disease.

In 1971 participants in the Ann Arbor Conference on Hodgkin's disease thought that pruritus had no independent prognostic importance. We reviewed our series of patients with Hodgkin's disease and found six patients in whom severe itching was a major clinical problem. When compared with similarly treated patients without pruritus, these patients appeared to have more-aggressive disease. Severe itching, alone or with B symptoms, needs further study, since it may presage a poor prognosis.

Adult↗
PubMed1978

Lack of usefulness of bone marrow enzymes and calcium in staging patients with prostatic cancer.

Bone marrow acid phosphatase has been reported to be a sensitive indicator of early bony metastasis from adenocarcinoma of the prostate. In order to evaluate this hypothesis, we measured bone marrow acid and alkaline phosphatase, lactic dehydrogenase, and calcium levels in a group of 84 patients with a variety of problems, including 18 with cancer of the prostate. We found that the bone marrow acid and alkaline phosphatase and lactic dehydrogenase were elevated and calcium was depressed in most patients. Among patients with prostate cancer, bone marrow acid phosphatase was not significantly different between those with or without bone metastases. In addition, the patients with prostatic cancer did not have higher levels of bone marrow acid phosphatase than subjects with other malignant and nonmalignant conditions. The level of acid and alkaline phosphatase, lactic dehydrogenase and calcium varied predictably with the aspiration technique used and was independent of sex, disease state or method of chemical determination. Due to this variation, we believe that bone marrow enzyme and calcium levels are of no value in the detection of metastases in patients with prostate cancer.

Acid Phosphatase↗
PubMed1978

Variables predictive of bone marrow metastasis.

Metastasis to bone marrow, though frequently occult, is an important clinical finding. Variables which correlate with carcinoma metastatic to bone marrow were studied retrospectively in 103 patients with malignancy whose bone marrow biopsies demonstrated metastatic disease. Sixty-six patients with metastatic cancer whose bone marrow biopsies were negative, served as controls. Since no single finding was diagnostic of marrow cancer, multiple variables were analyzed by stepwise discriminate analysis program. The four parameters which strongly correlated with marrow involvement were the leukoerythroblastic blood pattern, a serum lactic dehydrogenase over 500 IU/liter, a platelet count under 100,000/microliter and bone pain. Four parameters correlated less well and included a positive bone scan, hematocrit under 30%, uric acid over 10 mg/dl and blood urea nitrogen over 25 mg/dl. These data should help the clinician select those cancer patients with a high probability of marrow involvement.

Blood Cell Count↗
PubMed1978

The anemia of chronic renal failure: studies of the effect of organic solvent extraction of serum.

CRF serum contains a material(s) which is inhibitory to erythropoiesis in vitro. The chemical nature and mechanism of action of this material are unclear at the present time. To further study this problem, we extracted NL serum and CRF serum samples with two organic solvents, chloroform and petroleum ether. The serum samples were studied before and after extraction in a tissue culture system in which dog erythroblasts were stimulated by EP to synthesize heme. Before extraction, cells suspended in CRF serum synthesized less heme than cells cultured in NL serum. Extraction of CRF serum with chloroform, but not petroleum ether, resulted in an improvement in its ability to support heme synthesis. Studies of the material extracted by chloroform from CRF serum showed that it was inhibitory to erythropoiesis. We propose that the erythropoietic inhibitory substance in uremic serum in soluble in chloroform but not in petroleum ether, suggesting that it is a polar lipid.

Anemia↗
PubMed1978

The effect of serum from patients with chronic renal failure on erythroid colony growth in vitro.

Considerable evidence suggests that insufficient EP production and the presence of a toxic factor inhibiting erythropoiesis are two major factors responsible for the production of anemia in patients with CRF. The toxic factor can be detected in a number of tissue culture systems. In order to evaluate its mechanism of action in a proliferation-dependent system, we studied the formation of erythroid colonies in plasma clots containing normal serum and CRF serum, using normal mouse marrow cells as the target organ. Fewer colonies were found in cultures containing uremic serum. This effect was greater as the concentration of serum was increased. No differences were found in the size or morphology of colonies formed. Addition of urea and creatinine to normal sera did not affect their ability to support colony growth. Uremic sera had no effect on white cell colony growth in the plasma clot system. We conclude that materials inhibitory to erythroid proliferation are present in CRF serum.

Animals↗
PubMed1977

Levels of erythropoietin in patients with the anemias of chronic diseases and liver failure.

Two mechanisms are felt to be responsible for the production of anemia in patients with chronic diseases. The first is failure to produce adequate amounts of erythropoietin (EP), and the second is failure to deliver iron to the bone marrow in amounts sufficient to support normal erythropoiesis. In order to evaluate these hypotheses we studied urine and serum EP levels and levels of 2,3-diphosphoglycerate in normal subjects, in patients with the anemia of chronic diseases, in patients with chronic liver disease, and in patients with a variety of other anemias. Based on the results, we propose first that insufficient production of EP is one of the major mechanisms responsible for anemia in patients with chronic diseases. Second, insufficient production of EP is, in part, responsible for anemia seen in patients with chronic liver disease. Third, serum and urine EP levels decrease with aging, and this correlates with the fall of hemoglobin levels seen in older normal subjects.

Aging↗