Biomedical subjects
Publications and source records attributed to D R Miller.
An unusual case of acute leukemia with basophilic cytoplasmic inclusion bodies in a child is described. Certain aspects of the case suggested a lymphoblastic phenotype and others a myeloid origin. The inclusions stained positively for acid phosphatase and toluidine blue. Too few patients have been reported to determine the prognostic significance of acute leukemia with inclusion bodies.
Explore the source record for details and available documents.
The macrocreatine kinase type 2 isoenzyme (MCK-2) was investigated as a marker for colonic cancer. It was sought in 252 serum samples from 231 patients: 69 with active colonic cancer, 49 in whom colonic cancer had been successfully resected, 58 with nonmalignant diseases of the colon, and 76 patients immediately following colonic surgery. MCK-2 was detected in the serum of 39 of the patients with cancer (57%) and in one patient with diverticulitis. MCK-2 and carcinoembryonic antigen (CEA) were both measured in 47 colonic cancer patients. Both markers were detected in 19 cases, MCK-2 alone in eight and CEA alone in eight. We conclude that MCK-2 is a promising tumor marker for carcinoma of the colon and that its value might be complementary to that of CEA.
The relation between the risk of breast cancer and the use of noncontraceptive estrogens was investigated in a hospital-based study of 1,610 women with breast cancer and 1,606 with other conditions. The overall relative risk estimate for conjugated estrogens first taken at least 18 months before admission, compared with never-use of any noncontraceptive estrogens, was 0.9 (95% confidence interval, 0.7 to 1.1). For other estrogens first taken at least 18 months before admission, the estimate was 0.8 (0.6 to 1.1). The results were similar when known risk factors for breast cancer were taken into account. Among postmenopausal women, conjugated estrogens did not appear to increase the risk of breast cancer, even when taken for many years or in the distant past. There was no evidence of an increased risk due to conjugated estrogen use among subgroups of women defined according to various risk factors for breast cancer. The results of this study suggest that noncontraceptive estrogens do not increase the risk of breast cancer.
It has been suggested that cigarette smoking may reduce the incidence of breast cancer, perhaps by as much as 20 per cent. To evaluate the relation between breast-cancer risk and smoking, we studied 2160 women with breast cancer and 717 controls who had been admitted to the hospital for cancer of the ovary, cancer of the colon or rectum, malignant melanoma, or lymphoreticular cancers. As compared with women who had never smoked, the estimated relative risk of breast cancer was 1.1 for current smokers of any amount (95 per cent confidence interval, 0.9 to 1.3), and 1.0 (0.8 to 1.3) for heavy smokers (15 or more cigarettes per day). Allowance for all identified potential confounding factors did not materially alter the results. There was no indication that age at commencement of smoking was related to the risk, nor was there evidence of an effect of smoking within the categories of age at first pregnancy or age at menopause. The data provide evidence against the hypothesis that smoking may reduce the incidence of breast cancer by 20 per cent.
Staphylococcus epidermidis is emerging as a cause of morbidity and mortality in immunocompromised patients. From January 1980 through June 1982, there were 150 episodes of septicemia in 92 children with leukemia and lymphoma at Memorial Sloan-Kettering Cancer Center, New York. Staphylococcus epidermidis was the fourth most common organism isolated, responsible for 12.7% of all septicemic episodes. Only nine of 53 isolates were sensitive to methicillin; all were sensitive to vancomycin. Staphylococcus epidermidis septicemia was associated with immunosuppressive chemotherapy (94.7%); broad-spectrum antibiotics (79.0%); catheters and drains (73.7%); neutropenia (63.2%); skin or soft-tissue infections (42.1%); prior septicemia (42.1%); concurrent polymicrobial septicemia (21.1%); and prolonged hospitalization (mean, 39 days). Of 19 patients, two died. Increased awareness of the pathogenic potential of S epidermidis in children with hematologic malignancies and prompt alteration of therapy to an effective antimicrobial agent, in most cases vancomycin hydrochloride, is required when the organism is isolated in patients known to be at risk with clinical evidence of septicemia.
The diagnosis of idiopathic pulmonary hemosiderosis (IPH) may be elusive. A 6-year-old boy had microcytic hypochromic anemia and a hemolytic component. Hemosiderin-laden macrophages were not found in the gastric aspirate. He had no pulmonary signs or symptoms. Extensive hematologic and roentgenologic investigations failed to reveal the cause of the anemia. Quantitative serial scintigraphic scanning showed significant (35%) pulmonary sequestration of autologous erythrocytes labeled with sodium chromate Cr51. The half-life of the RBCs was moderately decreased (half-life, 15 days; normal, 25 to 35 days). An open-lung biopsy specimen confirmed the diagnosis of IPH. A diagnosis of IPH should be considered when children have iron deficiency anemia and pulmonary signs or symptoms. Organ sequestration studies may be helpful in equivocal cases.
We retrospectively reviewed the clinical data of 17 selected patients who underwent hepatobiliary imaging studies using technetium Tc 99m iprofenin that demonstrated acute complete common bile duct obstruction, and who also had a temporally related ultrasonographic study of the hepatobiliary tree. We compared the accuracy of the two methods in the detection of common duct obstruction. The average duration of symptoms was 2.9 days. Serum bilirubin levels averaged 3.3 mg/dL and the average alkaline phosphatase level was 336 mg/dL. The serum amylase level was elevated in only three patients. Ultrasonographic dilatation of the ductal structures was present in seven (41%) of 17 patients; 88% of the patients had other manifestations of gallbladder disease on ultrasonography--either cholelithiasis, dilatation of the gallbladder, or wall thickening. Of 15 patients who were operated on, 11 had stones impacted at the ampulla of Vater. There was a poor correlation of ultrasonographic ductal dilatation and operative findings of ductal dilatation. This study shows the superiority of nuclear imaging over ultrasonography in the early detection of acute, common bile duct obstruction.
An 8-month-old male with acute monoblastic leukemia died during induction chemotherapy of severe bleeding refractory to repeated infusions of platelets and clotting factors. A heparin effect was suggested by prothrombin time (PT) of 26 seconds, partial thromboplastin time (PTT) of 94 seconds, thrombin time 240 seconds, and reptilase time 18.4 seconds, with a fibrinogen of 88 mg/dl. Both plasma mixed with the patient's urine and the patient's plasma had their thrombin times corrected toward normal by both PF4 and protamine. Synergism of the anticoagulant with antithrombin III was demonstrated not only by enhanced inhibition of thrombin but also by an increased rate of formation of thrombin--antithrombin III complexes in the presence of the anticoagulant, which was eliminated by preincubation with heparinase. Since the anticoagulant activity was not found in the blasts themselves, it is presumed that the anticoagulant is heparin/heparan liberated from the endothelial lining by products of the cell destruction secondary to chemotherapy.
Cerebrospinal fluid of 24 patients with acute leukemia was studied by DNA/RNA flow cytometry. In six of 15 patients with central nervous system (CNS) relapse, the spinal fluid cells had abnormal DNA stemlines, ranging from near haploid to hyperdiploid. In two additional cases, leukemic cells were identified by a abnormally high RNA content only. One patient had two different aneuploid cell populations in spinal fluid not distinguished by cytologic morphology. Another patient with initial diploid leukemia had CNS relapse characterized by the same DNA stemline long after a triploid DNA stemline emerged in the marrow. DNA/RNA flow cytometry detected leukemic cells that were not identified ("uniform" or "reactive") by cytological criteria in 5/6 patients studied and in addition differentiated lymphoblastic from nonlymphoblastic cell types according to low and high RNA content.
Serum lactate dehydrogenase activity (LDH) was examined in 66 children with acute lymphoblastic leukemia (ALL), 26 with acute non-lymphocytic leukemia (ANLL), and 116 with non-Hodgkin's lymphoma (NHL). The mean serum LDH value for the ALL and ANLL groups was not significantly different: 970 +/- 105 units/L (mean +/- standard error of the mean) and 817 +/- 161 units/L, respectively. The difference between the LDH values in patients with ALL (970 +/- 105 units/L) and NHL (551 +/- 51 units/L) was significant (P = .001). In 32% of the patients with ALL and 23% of the patients with ANLL, serum LDH values were above 1000 units/L, whereas only 13% of the cases with NHL had values above 1000 units/L. In patients with ALL the LDH levels were correlated with white blood cell counts at the time of diagnosis. In NHL, there was no difference in serum LDH levels among the various histologic subtypes. Values of LDH in stage IV NHL and in ALL were similar.
Upon exposure to methylmercury chloride, the whole-cell oxygen uptake by the yeast Saccharomyces cerevisiae ceases. On a fermentable carbon source, carbon dioxide continues to be evolved after respiration has stopped, indicating that fermentation is still active. Dextrose and glycerol uptake also persists until the respective processes, fermentation and respiration, are totally inhibited. Protein and nucleic acid synthesis are blocked with similar concentrations of methylmercury, while cytochrome c, the terminal component of the electron transport chain, is unaltered by the toxicant. Surprisingly, the intracellular ATP is higher in the treated cells than in the controls, although they eventually fall in response to higher concentrations of methylmercury, while cytochrome c, the terminal component of the electron transport chain, is unaltered by the toxicant. Surprisingly, the intracellular ATP is higher in the treated cells than in the controls, although they eventually fall in response to higher concentration or longer exposure. High-pressure liquid chromatography profiles show that the amounts of the other nucleotides are either unaltered or increased. The entire inhibitory process is reversible with time or fresh medium at low methylmercury concentrations. These results do not support the hypothesis expressed by several authors of an inhibition of ATP biosynthesis resulting from membrane perturbation. These data suggest that the decrease in ATP--when induced by the organomercurial--is a secondary process and is not the result of direct mitochondrial toxicity.
It has been reported that the addition of nonaggregating concentrations of collagen, epinephrine, thrombin or arachidonic acid to platelets potentiate their responses to subsequent subthreshold concentrations of aggregating agents. We have previously reported that low concentrations of methylmercury will potentiate human platelet ATP secretion and that this effect is blocked by aspirin. Using rat platelets we have examined the effect of low concentrations of methylmercury on the metabolism of arachidonic acid. Low concentrations of methylmercury (20-100 microM) inhibit washed platelet lipoxygenase activity. In experiments using platelet rich plasma a higher concentration of methylmercury was required to produce a comparable inhibition of arachidonic acid metabolism. At these concentrations no inhibition of platelet thromboxane synthetase was seen. These findings suggest that methylmercury potentiates platelet aggregation and secretion by reducing the inhibitory effect of 12 HPETE on thromboxane biosynthesis.
Guinea pigs were given radiolabelled methyl(203)mercuric chloride at a dose of 3 mg/kg p.o. alone or with an equimolar dose of sodium selenite, every second day for 3 weeks (10 doses). Whole-body mercury levels were measured during the course of the study and multi-compartment analysis carried out by computer least-squares curve fitting. Results indicated that mercury given alone behaved according to a single compartment model with half-life of 23.6 days, while in the presence of selenium a two-compartment behaviour resulted with one clearing rapidly (half-life 8.7 +/- 5.3 days) and the other clearing more slowly (half-life 40.8 +/- 13.0 days). Selenium decreased excretion of mercury in feces (2-fold) and urine (7-fold). Approximately 70% of the total mercury in the feces and 90% of that in the urine was in organic form. Tissue distribution of total, organic and inorganic mercury was determined 1, 14 and 28 days after the final dose. Selenium decreased the levels of mercury 1 day after the final dose, but produced a slower clearance after that. In all organs examined most of the mercury was in the organic form, except in the kidney which had over 70% inorganic mercury. Selenium increased the relative amounts of inorganic mercury in the liver, spleen, pancreas, large and small bowels, but not in the kidney.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The risk of breast cancer in relation to oral contraceptive use was evaluated in a case-control study of 1191 patients with breast cancer and 5026 control patients. For ever-use compared with never-use, the estimated relative risk of breast cancer was 1.0 (95% confidence interval 0.9-1.2). Use of oral contraceptives for five or more years was not associated with breast cancer, regardless of whether use had ended as much as 10 or more years previously, or more recently. Within categories of women whose baseline risk was elevated, including nulligravidae, premenopausal women, and those with benign breast disease or history of breast cancer in first-degree relatives, the relative risk estimates for five or more years of oral contraceptive use approximated 1.0. For any use before first pregnancy, the relative risk estimate was 1.3, and for use lasting three or more years it was 0.9. These data suggest that long-term oral contraceptive use does not increase the risk of breast cancer even after a latent interval in excess of one decade; nor do oral contraceptives appear to increase the risk within categories of women at relatively high baseline risk.
A therapeutic synergistic effect is seen in animal models when vinca alkaloids are administered after methotrexate. To examine further this interaction in clinical studies, a phase I-II trial was conducted in children with hematologic malignancies in the Department of Pediatrics at Memorial Sloan-Kettering Cancer Center. A schedule of sequential of methotrexate and vindesine was developed which showed effect in acute lymphoblastic leukemia in children in relapse and which was relatively nontoxic. The regimen has also been useful for reinduction for patients who are candidates for bone marrow transplant.