Bone marrow transplantation for acute leukemia and lymphoma with high-dose cytosine arabinoside and total body irradiation.
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Acute Disease↗
Biomedical subjects
S Gross
Publications and source records attributed to S Gross.
Congenital nuclear cataracts in the Morgan horse.
Nuclear cataracts were found in 2 groups of related Morgan horses. The cataracts were finely reticulated central spherical translucencies that sometimes extended to the region of the posterior "Y" suture. The cataracts were not associated with other ocular defects and did not impair vision. In 1 group of 8 horses, 5 were affected; in the other group, 6 of 8 were affected. Although a pattern of inheritance could not be determined, the familial distribution of the cataracts supported the conclusion that the defect was a heritable disorder.
Animals↗
Improved response of patients refractory to random-donor platelet transfusions by intravenous gamma globulin.
Because of frequent unavailability of HLA-compatible platelets or their inefficiency in increasing platelet counts in patients requiring platelet transfusions, platelet refractoriness remains a major problem. Since human gamma globulin has been shown to interfere with the binding of platelet-reactive immunoglobulin G (IgG) to platelets in vitro, and since gamma globulin has proved effective in reversing destruction of platelets in idiopathic thrombocytopenic purpura, we decided to investigate intravenous gamma globulin as an adjunct to random-donor platelet transfusions. We studied three patients, one with acute T-cell leukemia, and two with aplastic anemia. When a total dose of 2 g/kg of body weight of intravenous gamma globulin was infused over five to six days in these patients, two of them showed a remarkable increment in platelet counts and improved hemostasis with random-donor platelet transfusions. We conclude that intravenous gamma globulin may be used in critical situations to improve the response of patients refractory to random-donor platelet transfusions.
Adult↗
The effects of PGF2 alpha, PGI2, and TxB2 on human CFU-C in healthy and leukemic patients.
This study was undertaken to test the effects of certain arachidonate derivatives, PGF2 alpha, PGI2 and TxB2 on in vitro bone marrow granulocyte colony growth (CFU-C) in leukemia patients receiving maintenance chemotherapy and in normal controls. The addition of PGF2 alpha did not result in increased numbers of colonies, but it did cause a shift in the size of the colonies so that there was a significant increase in larger colonies (P less than 0.001) and significantly fewer small colonies (P less than 0.05) as compared to untreated samples. Of the prostenoids tested in a Tris-buffered system, PGI2 affected the greatest increase in CFU-C (P less than 0.01) followed by PGF2 alpha (P less than 0.05) whereas 6-keto-PGF1 alpha (the stable hydrate of PGI2) did not affect colony growth. Time-response curves revealed a linear growth pattern for PGF2 alpha with a peak at 10 days, whereas there was a 6-day growth lag with PGI2 followed by linear growth with a peak at 13 days. TxB2 added to cultures significantly reduced the number of bone marrow CFU-C at all doses tested. The prostanoid effects on CFU-C derived from leukemic patients on maintenance chemotherapy and from normal individuals were identical in every respect.
Adolescent↗
Cimetidine suppression of CFU-C in males.
A presumed cimetidine-induced granulocytopenia in a 6-year-old male with acute lymphocytic leukemia (ALL) prompted an investigation of the effects of cimetidine on in vitro bone marrow granulocyte colony growth (CFU-C) in normal individuals and ALL patients either on maintenance chemotherapy or off all therapy for at least 1 year. The addition of cimetidine resulted in a significant reduction of colony numbers as compared to untreated controls beginning at 1 x 10(-6) M (P less than 0.05) and increasing in significance as the concentration of cimetidine increased. Analysis of sex differences showed that CFU-C derived from females were not adversely affected by the addition of cimetidine (except at levels far in excess of recommended dosages) whereas CFU-C in males declined significantly from controls beginning at 1 x 10(-7) M (P less than 0.05) and became of greater significance as the concentration of cimetidine increased. These findings were identical for both normal individuals and ALL patients either receiving maintenance chemotherapy or off all therapy.
Adolescent↗
Thorn-induced non-specific granulomatous left biceps myositis with left subareolar lymphadenopathy.
In surveying the pediatric and orthopedic literature, very little has been written about foreign bodies in skeletal muscle or muscle tissue inflammation in response to foreign bodies. When it is known that a foreign body has penetrated the muscle or if it is externally visible, there is no diagnostic problem. However, this can become a perplexing problem when history and physical examination are not clearly diagnostic. We present a case in which a thorn penetrated the left biceps muscle of a 10-year-old girl. The thorn remained there for 3 weeks without disturbing the child. It produced a local sterile granulomatous reaction in the muscle. Two weeks later, left subareolar lymphadenopathy appeared with no involvement of the axillary lymph nodes.
Arm↗
High-dose melphalan therapy for the treatment of children with refractory neuroblastoma and Ewing's sarcoma.
Neuroblastoma and Ewing's sarcoma are examples of pediatric cancers in which disseminated disease is often present at diagnosis or develops later in spite of combination therapy. The demonstration that marrow-ablative doses of chemotherapy can increase tumor cell kill, and that autologous bone marrow can be cryopreserved and reinfused into the patient to reverse such marrow ablation, has stimulated interest in this approach to refractory childhood cancers. We present results of treating eighteen patients with recurrent neuroblastoma and Ewing's sarcoma resistant to conventional therapy. We used supralethal doses of melphalan, supported by reinfusion of previously cryopreserved autologous bone marrow. Seven of 10 neuroblastoma and six of eight Ewing's sarcoma patients had complete or partial responses, lasting for a median of 6 months (neuroblastoma) and 3 months (Ewing's sarcoma). Prolonged hospitalization, pancytopenia complicated by sepsis, and reversible gastrointestinal toxicity were the major side effects. These results suggest this approach should be tested in therapeutic trials at an earlier disease stage in children who have cancers with a predictably bad prognosis.
Abdominal Neoplasms↗
Incidence of acute graft-versus-host disease with and without methotrexate prophylaxis in allogeneic bone marrow transplant patients.
Methotrexate has been used as the mainstay therapy to prevent or ameliorate graft-versus-host disease (GVHD) in allogeneic bone marrow transplantation. We began a nonrandomized study in which methotrexate was not given routinely. Fifty-five patients underwent transplant for acute leukemia (44 patients), aplastic anemia (6 patients), and other malignancies (5 patients). Methotrexate was given to 34 patients (MTX +) and was withheld in 21 patients (MTX -). Median (range) age of patients was 12 (0.8-43) years in the MTX + group, and 16 (3-45) years in the MTX- group. Mean days (+/- SEM) to engraftment (neutrophils greater than 500/microL, and platelets greater than 20,000/microL untransfused) occurred earlier in the MTX- patients (19.6 +/- 1.4 v 24.9 +/- 1.8 days for granulocytes, and 19.3 +/- 1.5 v 27.4 +/- 2.8 days for platelets, P less than .05). There were no statistically significant differences between the patient groups for the incidence or severity of GVHD (10/34 in the MTX + group had grade O-l GVHD compared to 9/21 in the MTX- group). The interstitial pneumonitis occurred at a significantly increased rate in patients who received methotrexate (15/34) compared to those patients who did not (3/21) (P = .02). However, there was also a significant relationship between the interstitial pneumonitis and the preparative regimen: if the preparative regimen contained 1,000 rad single fraction total body irradiation, 8/14 patients were affected compared to 5/22 patients affected when 1,200 rad fractionated total body irradiation was used (P = .03). Because methotrexate significantly retards hematopoietic reconstitution, randomized trials for GVHD prevention are recommended.
Acute Disease↗
Bone marrow transplantation. Current limitations and future utilization.
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Animals↗
United States experience with oxprenolol in hypertension.
Double-blind, randomized, parallel-group studies have confirmed that oxprenolol, either alone or in combination with a thiazide, is effective in reducing elevated blood pressure. In 2 of 3 comparisons with placebo, the blood pressure reduction was significantly more effective with oxprenolol; in 1 study, even though the placebo response was pronounced, oxprenolol was still more effective than placebo. In 2 studies propranolol reduced blood pressure by about 2 mm Hg more than oxprenolol. In the larger, longer-term study this difference was significant at the end of the dose-titration period, but there were no significant differences between the 2 treatment groups at study end. Moreover, oxprenolol reduced heart rate less and was associated with fewer side effects. Oxprenolol effectively lowered blood pressure when given once daily and was well tolerated, even in large doses. Blood pressure was reduced less with oxprenolol than with hydrochlorothiazide, -14/-11 versus -20/-13 mm Hg. The mean reduction with oxprenolol was less for black patients than for white. In a 1-year safety study, 86% of the patients continued to have a diastolic pressure of less than 90 mm Hg at study end.
Blood Pressure↗
Cyclic parenteral nutrition during bone marrow transplantation in children.
Nine children underwent ten bone marrow transplants for malignancies and were supported by parenteral alimentation administered in cyclic fashion 18 hours daily. Children received cyclic parenteral nutrition for an average of 29 days, which provided a caloric intake (mean +/- SD) of 55.9 +/- 18.1 Kcal/kg/day, and a nitrogen intake of 0.28 +/- 0.08 g/kg/day. Nutritional status was assessed using nitrogen balance, creatinine-height index, and visceral protein concentrations including serum albumin, transferrin, and prealbumin. Minimal transient elevation in tests of liver function were observed without marked derangement in blood glucose, electrolytes, or osmolality. Unlike prealbumin, determinations of nitrogen balance, creatinine-height index, serum albumin and transferrin concentrations did not parallel changes in clinical status. Cyclic parenteral alimentation is a practical approach to the maintenance of nutrition during intensive antitumor therapy and provides an infusion-free period for the administration of drugs and blood transfusions without interfering with nutritional support. Prealbumin accurately reflects changes in the patient's clinical status at any point and is easily and reliably determined.
Adolescent↗
Tumor and urine catecholamines (CATs) in neurogenic tumors. Correlations with other prognostic factors and survival.
This study was undertaken to better define the relationship between catecholamine (CAT) metabolism within the malignant neuroblast and other factors known to influence clinical outcome in neuroblastoma (NB). Several CATs and their metabolites were measured in 32 tumors and 47 urines from 60 newly diagnosed children with neurogenic tumors. Absolute and relative CAT concentrations were correlated with age, clinical stage, histologic differentiation and survival duration. The major findings are: (1) urinary CAT excretion patterns often differ markedly from tumor CAT patterns in the same child, which may be explained by the continuous nature of tumor metabolism, hepatic and renal catabolism, and sampling errors; (2) definite patterns of biochemical maturation are apparent in tumors and urines, but standard light microscopy is insufficient to correlate this with degree of histologic differentiation; (3) more differentiated patterns of CAT metabolism, both in tumor and urine, are significantly associated with age less than 1 year at diagnosis, and with more favorable clinical Stage (I, II, IVS). Tumor NE was increased relative to DM and DA, and urine NMN and VMA were increased relative to DM and HVA, in these patients. (4) this more differentiated CAT pattern in infants and in less advanced stages was reflected in their better survival. Greater maturity of tumor enzyme systems is the probable reason for the better prognosis of NB in infants less than 1 year. Individual enzymes should be measured in fresh tumor tissues, and related to relative and absolute CAT concentrations in tumor and urine, to try to categorize patients on the basis of clearcut biological differences when planning new treatment strategies for NB.
Age Factors↗
A double-blind study of oxprenolol once and twice daily in hypertensive patients.
In a randomized double-blind study of 175 patients with mild-to-moderate hypertension, oxprenolol hydrochloride (160-480 mg) given once daily was compared with the same drug given twice daily for efficacy, safety, and tolerability. Of these patients, 123 (58 receiving the once daily regimen and 65 receiving the twice daily regimen) were included in the analysis of efficacy. Both groups showed similar significant (p less than 0.01) reductions in mean blood pressure during the 6-week titration period and for the remainder of the trial. A comparison of mean standing diastolic blood pressure and supine systolic and diastolic blood presses showed no significant difference between groups during the fixed dosage period. The number of patients reporting adverse experiences was not significantly different for the two regimens. Plasma triglycerides increased in both groups, but there were no other laboratory abnormalities related to treatment. This study shows that oxprenolol given once daily is effective, safe, and well tolerated in the treatment of mild-to-moderate hypertension.
Adult↗
Analgesic properties of meperidine, amitriptyline and phenelzine in mice.
Sixty-three white Swiss Webster mice were divided into seven equal groups. Their tolerance to pain (heat applied to the tail by a test tube containing hot water at a temperature measured by telethermometry) was assessed before and after intraperitoneal injection of (1) physiologic saline; (2) meperidine 14 micrograms X g-1; (3) amitriptyline 6 micrograms X g-1 (4) amitriptyline 12 micrograms X g-1; (5) phenelzine 1.5 micrograms X g-1; (6) phenelzine 3 micrograms X g-1; and (7) amitriptyline 6 micrograms X g-1 plus phenelzine 1.5 micrograms X g-1. All post-injection tests were conducted 45 and 90 minutes after administration, and repeated 24 hours later. No significant difference in pain threshold was noted in any pre-injection test or in any test conducted with physiologic saline. By 90 minutes post-injection, all groups receiving drugs developed increased tolerance to pain. Mice which had received phenelzine plus amitriptyline, or either dose of phenelzine were more tolerant to pain for up to 24 hours than mice which had received physiologic saline. The most marked increases in tolerance to pain were seen with 1.5 micrograms X g-1 and 3 micrograms X g-1 of phenelzine and phenelzine plus amitriptyline. However, phenelzine was more effective and had a longer-lasting effect than either dose of amitriptyline, or meperidine. The combination of phenelzine plus amitriptyline was no more effective than phenelzine alone.
Amitriptyline↗
Slow-release oxprenolol compared with oxprenolol in hypertensive patients: a multicenter clinical trial.
Oxprenolol (OX) is a nonselective, beta-adrenergic blocking agent with intrinsic sympathomimetic activity. We studied 178 patients in five centers to determine whether a polymer-matrix-based, slow-release preparation of oxprenolol (SR-OX) given once daily was as effective as the standard preparation given twice daily for the treatment of patients with mild to moderate hypertension. After a placebo washout phase, patients were treated with OX until blood pressure was controlled. They were then randomized in a double-blind fashion to continue the same dose, given as either OX bid or SR-OX qd with a placebo as the second dose. All patients took hydrochlorothiazide 50-100 mg/d throughout the study. Blood pressure was reduced 23/15 mm Hg (p less than 0.001) and pulse 8 beats/min in the SR-OX group (n = 67) and 24/17 mm Hg (p less than 0.001) and 8 beats/min in the OX group (n = 72) by titrating standard OX. After randomization to SR-OX or OX, there were no further changes over six weeks. Home-determined blood pressures showed no loss of control in the evening. There were no unexpected adverse effects. We conclude that SR-OX given once daily is as effective as OX given twice daily for the treatment of hypertension.
Adult↗
Neonatal hematological problems.
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ABO Blood-Group System↗
Mitral anulus and valvular calcification.
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Aged↗
Intrauterine exposure to halothane increases murine postnatal autotolerance to halothane and reduces brain weight.
The effect of halothane on prenatal development was assessed using the appearance of postnatal tolerance to the anesthetic and its effect on brain weight. Eighteen 3-month-old mice were repeatedly tested in a rotating cage for loss of righting reflex during exposure to increasing concentrations of halothane on 15 occasions to determine whether or not tolerance to halothane developed. Of these, nine mice were born to dams exposed for 30 min to 2% halothane on days 14 and 17 of gestation. The other nine mice (controls) were born to dams exposed to 100% oxygen for 30 min at the same stage of pregnancy. There was no significant difference in tolerance to halothane between the groups during the first nine days of repeated exposure to halothane. By the 13th and 15th days, however, mice exposed to halothane in utero became more tolerant to 1% halothane than did controls (P less than 0.025). In addition, the mean total brain weight of six 7-week-old mice exposed to 2% halothane in utero for 30 min on days 14 and 17 of gestation was found to be significantly less than the mean total brain weight of six control mice not exposed to halothane in utero (20.83 +/- 0.27 g and 23.07 +/- 0.51 g, respectively, P less than 0.0025). This difference occurred mainly in the brain stem rather than in the forebrain and cerebellum.
Animals↗