Acridine orange potentiation of actinomycin D uptake and activity.

Acridine orange enhances the uptake of [(3)H]actinomycin D in disrupted and intact human lymphocytes, as measured by liquid scintillation and autoradiography. Proflavine, quinacrine, chloroquine, and ethidium bromide are not effective. In mice, acridine orange increases the capacity of actinomycin to reduce spleen weight. Type II acridine binding to DNA may be a prerequisite for actinomycin enhancement.

The effect of dead cells on the activity of actinomycin D against mouse sarcoma 180 ascites.

It has been demonstrated that cells killed by heat or irradiation have four times greater affinity for actinomycin D (AMD) than do viable tumor cells. By using a double labeling technique, we were able to show that, with increasing amounts of AMD bound in cells, the incorporation of RNA precursors is proportionally decreased. However, in the presence of nonviable cells or of native DNA, the AMD-induced inhibition of [3H]uridine incorporation is markedly reduced. This reduction does not occur if DNase is added to the system. The accumulation of dead cells in the tumor vicinity during the natural course of tumor growth or therapy must be taken into consideration in planning therapeutic regimens. We suggest that, in combined chemo- and radiotherapy, increased effectiveness of AMD may be obtained by its use prior to irradiation, thereby assuring its direct access to the tumor cells. The addition of DNase could eliminate or greatly diminish the dead cell competition for the drug.

Renal cell carcinoma in patients with tuberous sclerosis.

An adolescent with anemia and weight loss was found to have bilateral renal cell carcinoma (hypernephroma). Further investigation revealed an underlying tuberous sclerosis that had escaped previous clinical detection. Several reports of this association were subsequently found when the world's literature was reviewed. Physicians treating patients with tuberous sclerosis should be aware of the possible development of these renal malignancies in their patients.

False-positive FDG-PET imaging of the thymus of a child with Hodgkin's disease.

During the evaluation of a child who had completed treatment for Hodgkin's disease, a PET study strongly suggested recurrent disease in the mediastinum. Biopsies were obtained and revealed normal thymic tissue only, with no evidence of recurrent disease. The ongoing difficulty in establishing accurate disease status in patients treated for Hodgkin's disease is discussed, along with recommendations for treating pediatric patient populations.

Childhood acute lymphoblastic leukemia associated with an unusual 8;14 translocation.

An 8;14 chromosome translocation with the break points t(8;14(q11;q32) is described in bone marrow cells of a patient with null cell terminal deoxynucleotidyl transferase (TdT)-positive acute lymphoblastic leukemia. The patient, who is dysmorphic and mentally retarded, ha a normal 46,XY constitutional chromosome karyotype. A review of the more usual cytogenetic findings in this type of leukemia and a comparison of B-cell lymphoproliferative cytogenetic associations are presented.

Chronically transfused patients with increased hemoglobin Alc secondary to donor blood.

In an attempt to detect early evidence of hemochromatosis-induced diabetes mellitus, hemoglobin Alc (Hgb Alc) levels were determined in four patients treated with chronic transfusions. All four were found to have significantly elevated Hgb Alc levels on several occasions. On further investigation, it was discovered that elevated levels of glycosylated hemoglobin were present in donor blood stored in dextrose solutions, thus leading to a higher level in the recipients. Hemoglobin Alc levels appear to be unreliable in patients receiving large amounts of transfused blood.

Acquired coagulation inhibitor in association with Rocky Mountain spotted fever. With a review of other acquired coagulation inhibitors.

An acutely ill 4-year-old girl with Rocky Mountain spotted fever (RMSF) was found to have a coagulation inhibitor. This child had no serious bleeding manifestations and minimal hemorrhagic skin manifestations despite severe RMSF, concurrent thrombocytopenia, as well as the coagulation inhibitor. Hemostatic abnormalities that occur with RMSF as well as other infectious illnesses associated with coagulation inhibitors are reviewed.

The frequency of high/moderate lipoprotein risk factor for coronary artery disease is significant in juvenile-onset systemic lupus erythematosus.

To determine the prevalence of dyslipoproteinemia on a large juvenile systemic lupus erythematosus (jSLE) cohort, we selected 40 patients after rigorous exclusion criteria. Lipoprotein levels were determinated after 12 hours fast and risk levels for CAD were defined by standards of the Brazilian Guidelines for dyslipoproteinemia according to US-NCEP. All individuals were under steroid therapy and chloroquine and 43% had active disease. Thirty patients (75%) had high-risk levels for CAD (23 isolated low HDL, while in seven subjects low HDL was associated to high TG in four, high LDL in one, high TG/LDL in one and high TC/LDL in one). Remarkably, overall analysis revealed that 85% patients were included in high/medium risk levels group (29% for TC, 29% for LDL, 88% for HDL, and 18% for TG) and these disturbances occured mainly in the first four years of disease. Unexpectedly, one-third of the patients presented two or more high/medium lipoprotein risk factors. Independently, active jSLE was associated to TG (OR = 3.2; P < 0.001) and had a tendency towards reduction on HDL (OR = 8.5; P = 0.056). Considering improvements on jSLE outcome, the increased frequency of high/medium lipoprotein risk levels for CAD reinforces the need of prevention measures in order to minimize deleterious effects of this disturbance.

an unusual family cancer syndrome manifested in young siblings.

Three siblings whose mother had an ovarian mass excised as a teenager all developed malignancies in late childhood. Two were diagnosed as having malignant germ cell tumors of the ovary, whereas the third was found to have a soft tissue sarcoma. No underlying familial disease or constitutional chromosomal aberration has been detected and no known carcinogenic chemical exposure has been identified. All three children have been successfully treated with chemotherapy and are doing well off treatment. This is the first family cancer syndrome reported to have an association of ovarian germ cell tumors with embryonal sarcoma.

Further observations on the effects of lead implantation in rat brains.

Lead pellets were implanted into the forebrains of adult rats. Various cytoplasmic inclusions were found in macrophages, astrocytes, pericytes and microglia. Certain macrophages and reactive astrocytes displayed intranuclear inclusions as well. The hypothalamus, in some of the animals, showed sponginess which proved to be the result of swollen axons.

Some effects of intracerebral lead implantation in the rat.

Pellets of lead acetate were implanted into the forebrains of adult rats which were sacrificed at intervals between 4 days and 4 weeks thereafter. Parenchymal necrosis and a number of reactive changes including edema and macrophage invasion were observed. Lead deposits were found in the extracellular spaces and within macrophages but only to a slight extent within glial or meningeal cells. Vascular changes were quite remarkable and included proliferation and the appearance of fenestrated blood vessels as well as some with tubular bodies and striking increases in the number of pinocytotic vesicles.

Breast nodules as the initial site of relapse in childhood leukemia.

Two children with acute monoblastic leukemia in remission developed breast nodules that were the initial sites of disease relapse. Shortly after the appearance of disease in this site, the children developed marrow recurrence and, despite additional treatment, rapidly deteriorated and died from pancytopenia-related complications. The importance of careful breast examination is stressed as part of the surveillance physical examination for children with monoblastic leukemia.

Methyl mercury toxicity in the chick embryo.

The toxicity of methyl mercury (mHg) in the developing chick embryo was investigated. The relationship of dose, time of administration (i.e., days 4-9 of development), and body levels of mercury was examined. The LD50 for mHg injected into the yolk sac on day 5 of incubation was 40-50 micrograms. Embryos dying within 24 hours showed increased total body mHg levels when compared to survivors (219 +/- 67 vs. 105 +/- 41 micrograms/gm, mean +/- SD). Absorption was dose-related, with a good correlation between mortality and body, blood, and brain levels. Daily analysis of body mHg levels after injection on day 5 showed continued mHg accumulation (0.88 +/- 0.35 micrograms/embryo/day). However, the rate of embryo growth exceeded the rate of mHg absorption, resulting in a progressive decrease in mHg in concentration in tissues (from 94.5 +/- 34.2 micrograms/gm on day 6 to 45.3 +/- 13.4 on day 9). Administration after day 5 resulted in a significant reduction in levels of mHg in the brain on day 18 (from 11.4 +/- 2.1 micrograms/gm when given on day 5 to 8.4 +/- 2.3 when given on day 9) and in mortality (from 64% to 33%). Because blood mHg levels remained unchanged, the increased brain levels and higher mortality early in embryogenesis may reflect facilitated transfer of mHg across a poorly developed blood-brain barrier. Later in development, the reduced mortality and lower brain mHg levels correspond to the formation of specialized interendothelial junctions and a more effective blood-brain barrier.

In vitro studies on methyl mercury distribution in human blood.

Studies comparing the methyl mercury (mHg) content of maternal and newborn blood have shown increased levels in the newborn. This has been attributed to facilitated transplacental diffusion because of high fetal hematocrit (Hct). This study shows the converse, that the diffusion of mHg diminishes progressively with increasing Hct. The diffusion of m203Hg across a Millipore membrane (0.45 microns) separating compartments A and B of a diffusion cell was studied. When both compartments contained saline or plasma alone, equilibration from A to B occurred in 5 h. Introduction of human red blood cells (RBC) in saline (Hct 20%) into B resulted in a twofold increase in diffusion of mHg when compared to saline alone. Increasing Hct in saline in compartment B resulted in a progressive decrease in diffusion (r = -0.95, P less than 0.001). The presence of RBC in plasma (Hct 20%) in B resulted in a 70% decrease in diffusion; with increasing Hct, diffusion was further reduced (r = -0.95, P less than 0.001). Direct addition of mHg to RBC in saline resulted in 98% RBC uptake. Increasing concentrations of plasma (at a constant Hct) resulted in a progressive decrease in RBC uptake. In undiluted plasma at Hct 14%, RBC uptake of mHg was 35%. Plasma electrophoresis showed that much of the mHg was associated with a high-molecular-weight lipoprotein fraction. Plasma components appear to be important in the distribution of mHg in blood, and may be a factor in the relatively higher blood levels in the fetus.

Danazol for children with immune thrombocytopenic purpura.

Ten patients with steroid-dependent or refractory immune thrombocytopenic purpura were treated with danazol in an attempt to improve their platelet counts. Nine of the ten children exhibited an excellent initial response to the drug, with five achieving a complete, unmaintained remission. Two others were able to have their prednisone doses tapered with a resultant disappearance of steroid-induced adverse effects. No significant adverse effects of danazol were noted. Danazol seems to be effective in the treatment of children with immune thrombocytopenic purpura and would warrant additional studies to determine its proper role in the management of this common pediatric ailment.

Hyponatremia in sickle cell disease. A renal salt-losing state.

Severe hyponatremia has been observed in three children with sickle cell disease, and mild hyponatremia was noted during 36% of random hospitalizations for sickle crisis secondary to vasoocclusion or infection. Serum and urinary electrolytes were therefore studied in such patients. Hyponatremia was found in 52% of patients hospitalized with pain and/or fever, even though they received large amounts of sodium intravenously. Urine sodium losses were high with frequent negative sodium balance and weight loss. When well, these patients did not demonstrate hyponatremia, although urinary salt losses appeared to be just as high, suggesting compensatory salt intake when the children are well. It is essential to monitor electrolytes and urinary losses to manage sickle crisis properly. Six to 11 mEq/kg/day of sodium is suggested as a usual need of these patients during crisis. Sickle cell disease patients have, in addition to the better known defect in concentration of urine, a functional defect in dilution of urine at least during periods of "crisis".

Squamous cell carcinoma in the sacrococcygeal area: a case report and review of the literature.

Squamous cell carcinoma is a rare malignancy in the pediatric age group. We describe a 12-year-old boy with squamous cell carcinoma of the sacrococcygeal region. This is the first reported case of that pathology in this region. The patient was treated with surgery, chemotherapy and radiation therapy and is now free of disease 3 years later. The etiology of sacrococcygeal squamous cell carcinoma is unclear, and its possible pathophysiology in relation to its location is discussed.

Hemangioendothelioma with intravascular coagulation and ischemic colitis.

An infant who presented with a thigh mass and coagulopathy was found to have a hemangioendothelioma. The tumor rapidly enlarged despite accepted therapeutic modalities, and the child died after a sudden cardiac arrest. Postmortem examination revealed a highly invasive tumor mass that had infiltrated the bowel and involved the inferior mesenteric artery, resulting in ischemic colitis of the left colon. A discussion regarding the pathophysiology with respect to endothelial cell properties and other microscopic features of the tumor is presented.