Extension of myeloid tissue into the lower extremities in polycythemia.

Biopsies of the posterior iliac crest, greater trochanter, and proximal tibia were done for 27 polycythemic patients before myelosuppressive therapy was begun. Five had relative polycythemia, thirteen had secondary polycythemia, and nine had polycythemia vera. None of five biopsy specimens of the greater trochanter in cases of relative polycythemia contained myeloid tissue (erythroblasts, granulocytic precursors, and megakaryocytes). Four of six biopsy specimens of the greater trochanter and one of eight of the tibia in cases of secondary polycythemia contained myeloid tissue. All seven biopsy specimens of the greater trochanter and two of five biopsy specimens of the proximal tibia in cases of polycythemia vera contained myeloid tissue. A trochanter biopsy specimen devoid of myeloid tissue probably eliminates the diagnosis of polycythemia vera. Myeloid tissue extends from the axial skeleton to the greater trochanter, therafter to the tibia. Extension of myeloid tissue does not imply that marrow failure is imminent in polycythemia vera.

Colorectal cancer detection in a Community Hospital Screening Program.

In its first 4 1/2 years of operation in the Long Beach Community Hospital Cancer Detection Center, among the 5,595 persons examined, 16 cases of colorectal cancer were discovered. Fourteen of the 16 had symptoms referable to neoplasms. Eight had lesions found on proctosigmoidoscopic examination. Nine had positive findings for occult blood in stool samples, a 7.5% cancer detection rate among the 120 with positive stool sample findings. Six patients with cancer submitted one to four stool specimens that showed negative findings on occult blood testing, and one patient submitted no specimen. Although valuable in screening, stool testing for occult blood will not detect all colonic neoplasms. The complaints of pain, altered bowel habits, or tenesmus warrant sigmoidoscopic examination, barium enema studies, or both, whether findings in stool samples are positive or negative.

Chromosome deletion [46,XX,del(20)(q11)] in agnogenic myeloid metaplasia.

A woman in the fourth year of agnogenic myeloid metaplasia was found to have partial deletion of the long arm of chromosome 20 [46,XX,del(20)(q11)] in mitoses of presumably immature myeloid cells from unstimulated cultures of peripheral blood and bone marrow. Cytogenetic studies of peripheral blood lymphocytes showed a normal female karyotype.

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.

Acquired hemoglobin H in refractor sideroblastic anemia. A preleukemic marker.

Two patients with idiopathic refractory sideroblastic anemia (IRSA) were found to have acquired hemoglobin H. Both developed leukemic syndromes. Six other patients with IRSA had normal hemoglobin electrpohoretic patterns, and none has developed acute leukemia in up to five years. We suggest that hemoglobin electrphoresis be performed routinely in IRSA. The finding of hemoglobin H in this population may be a relatively frequent occurrence and may serve to distinguish the preleukemic patients from those not destined to develop leukemia.

Prolonged administration of bleomycin without clinical toxicity. Therapy with 2,700 units over four years.

A 26-year-old white man with stage 4-B Hodgkin's disease resistant to conventional chemotherapy obtained complete remission with administration of bleomycin. Maintenance of this remission required continued therapy with bleomycin. The patient received a total of 2,700 units of bleomycin over a 51-month period without signs or symptoms of pulmonary toxicity. Serial studies of pulmonary function have shown a stable forced vital capacity and minimally decreased total lung volume and pulmonary diffusing capacity. This case demonstrates the ability of a patient to tolerate massive cumulative doses ob bleomycin over a protracted period without severe loss of pulmonary function.

Granulopoietic and erythropoietic activity in patients with anemias of iron deficiency and chronic disease.

The serum levels of granulocyte colony-stimulating factor (CSF) and erythropoietin (Ep) were measured in 16 patients with iron-deficiency anemia and 15 patients with the anemia of chronic disease. Levels of both CSF and Ep in the serum of patients with iron-deficiency anemia had an inverse linear relationship to the level of the packed cell volume (PCV). There was no correlation between PCV and the levels of CSF or Ep in the serum of patients with the anemia of chronic disease. The similarity in the behavior of CSF and Ep in iron-deficiency anemia suggests that they may be influenced by similar control mechanisms or have a common cellular or molecular source.

Colony growth of normal human bone marrow in agar-gel.

A study of the colony forming ability of 99 normal human bone marrows using the semi-solid agar technique is presented. Feeder layers of 10(6) normal human peripheral white blood cells were used as the stimulus, and were overlaid with 2 X 10(5) bone marrow cells. The presence of human plasma either in feeder layers or bone marrow overlays inhibited colony formation when compared with studies performed with cells washed free of plasma. The number of colonies grown varied, but not significantly when the same marrow was grown on feeder layers from different donors. The inhibitory effect of normal human plasma was also demonstrated when unwashed and washed bone marrow cells were plated over feeder layers with no stimulus. Further confirmation of the inhibition by normal human plasma was made in 10 cases by the addition of 0.1 ml plasma to cultures of washed marrow over washed feeder layers. These data suggest that optimum results from in vitro culture of normal human bone marrow can be obtained only when all plasma is washed from both the feeder layer cells and the marrow cells before culturing.

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.

The effect of serum from uremic patients on erythropoietin.

Serum from patients with chronic renal failure (CRF serum) contains a substance inhibitory to erythropoiesis in vitro. This paper explores the mechanism of the inhibition. Four experiments were performed to evaluate the effects of CRF serum on erythropoietin (EP). In the first 2 experiments, the effect of exposure of EP solutions to CRF serum was evaluated using the plethoric mouse EP assay system and a tissue culture system containing normal dog marrow cells. In the third study, dog marrow cells were preincubated with CRF serum before being stimulated with EP. Finally, EP-dose response curves were constructed in the dog marrow tissue culture system and analyzed using an enzyme kinetic model. The results show no evidence of inhibition or inactivation of EP by CRF serum, although in vitro heme synthesis is clearly depressed in the presence of CRF serum. We conclude that CRF serum inhibits erythropoiesis by directly, although reversibly, impairing the ability of erythroblasts to synthesize heme.

Abnormal sella turcica. A tumor board review of the clinical significance.

Sixty of 146 patients with intracranial neoplasms or arterial aneurysms had roentgenographic abnormalities of the sella turcica. These abnormalities were most commonly due to chromophobe adenoma, craniopharygioma, and acromegaly, but ten of them were caused by lesions arising distant to the sella. There were also three cases of empty sella syndrome. Headache, visual disturbance, and sexual dysfunction were the most frequent presenting complaints, with visual field abnormality being most common. Pituitary dysfunction was manifested most frequently by alterations in growth hormone level and gonadotrophin secretion and less frequently by hypothyroidism and adrenocortical insufficiency. When the abnormal sella was associated with evidence of symptomatic intracranial disease, endocrine dysfunction, or visual field compromise as evidence of an anatomically aggressive intracranial neoplasm, specialized neuroroentgenographic localizing procedures were usually positive, and treatment for most of the causative lesions was highly effective.

Involvement of the heart and pericardium in the malignant lymphomas.

Seventeen patients with lymphomatous involvement of the heart or pericardium were studied. The series includes eight patients with Hodgkin's disease and nine with non-Hodgkin's lymphoma. All 17 had radiologia evidence of pulmonary, or mediastinal involvement. Cardiac or pericardial disease in seven was apparently due to direct extension of other intrathoracic tumor masses. Cardiac involvement was usually a late manifestation of lymphoma with median onset 20 months after initial diagnosis. Fourteen patients had been treated for stage IV disease prior to the onset of cardiac lymphoma. Only seven of the 17 patients with cardiac involvement were diagnosed antemortem. Four of them are alive without evidence of disease 8 to 68 months after diagnosis and treatment. Because cardiac lymphomas may respond to therapy with prolonged survival, it is imperative that clinicians suspect cardiac or pericardial involvement in lymphoma patients who have radiographic evidence of intrathoracic lesions (especially adjacent to cardiac borders), unexplained tachyarrhythmia or conduction disturbance, evidence of outflow obstruction, or signs and symptoms suggesting pericardial effusion or tamponade.

Felty's syndrome. Effect of lithium on granulopoiesis.

The effect of lithium carbonate upon granulopoiesis was studied in eight patients with Felty's syndrome. Absolute granulocyte counts increased in all patients receiving 900 mg lithium carbonate daily for six weeks. Increased urinary and serum granulocyte colony-stimulating activity was observed in all patients during lithium therapy. A casual relationship between increases in colony-stimulating activity and increased granulocytes is postulated.

The anemia of chronic renal failure and chronic diseases: in vitro studies of erythropoiesis.

The presence of a serum factor in chronic renal failure (CRF) which inhibits erythropoietin-stimulated erythropoiesis was studied, using a technique in which dog marrow cells were stimulated to produce heme in the presence of human serum. In the total series comparing 27 normal sera with 52 CRF sera, less heme was synthesized when the system contained CRF sera (total series, p = 0.0001). There was no evidence of inhibition of heme synthesis by serum from 12 patients with the anemia of chronic diseases (CD). Mixing experiments with normal and CRF sera suggested that this defect in CRF serum was not due to lack of a factor necessary for heme synthesis. Addition of urea, creatinine, and guanidinosuccinic acid to normal serum did not impair its ability to support erythropoiesis in this system. These data demonstrated that serum from patients with CRF contains a material inhibiting erythropoiesis in vitro, We propose that the material is responsible, in part, for the clinically severe anemia seen in these patients.

Bleomycin (NSC-125066) and CCNU (NSC-79037) in the combination chemotherapy of mopp-resistant hodgkin's disease.

Twenty-two patients with MOPP-resistant stage IVB Hodgkin's disease were treated with a combination of bleomycin and CCNU. The response rate in 18 patients surviving at least 1 month was 72% with 11 partial and two complete responses. The mean duration of response and survival in partial responders were 12.2 and 17.5 months respectively. The two complete responses resulted in survivals of 20 and 36 + months. Bleomycin toxicity contributed to two deaths, one pulmonary and and one hypotensive. Severe CCNU toxicity occurred after three of 82 administrations but there were no CCNU-related deaths. The majority of patients in the study tolerated the regimen without serious toxicity. Although highly effective in the temporary control of advanced resistant Hodgkin's disease, the program will hopefully be improved by the addition of longer-acting agents.