Correlation of chromosome abnormalities with patient characteristics, histologic subtype, and induction success in children with acute nonlymphocytic leukemia.

Cytogenetic analyses of bone marrow cells were performed in 195 children with acute nonlymphocytic leukemia (ANLL) at diagnosis, as part of Childrens Cancer Study Group Study No. 251. Ninety-six patients (49%) exhibited clonal abnormalities, including trisomy 8 in 18 patients, t(8;21) in 11, t(15;17) in seven, loss of a sex chromosome in seven, monosomy 7 in seven, and the Philadelphia chromosome in four. Clonal abnormalities were found significantly more often in younger patients. Furthermore, recurring cytogenetic abnormalities tended to correlate with specific ages. For example, t(8;21) was associated significantly with children over four years of age, while -7 associated with overall loss of genetic material from the long arm of chromosome 7 (7q) and 11q- were associated significantly with younger children. Recurring chromosome abnormalities also correlated with specific ANLL histologic subtypes, such as t(8;21) with acute myelogenous leukemia and t(15;17) with acute promyelocytic leukemia. Presence or absence of cytogenetic abnormalities was compared with the ability of patients to achieve remission. Individuals exhibiting clonal abnormalities in bone marrow cells had an equally likely chance of achieving remission (74%) as those individuals with normal karyotypes (75%). Nonrandom chromosome abnormalities associated with a high induction success rate included +8 with a 94% induction success rate (P = .13) and t(8;21) with a 91% success rate (P = .46). Patients exhibiting the -7 abnormality associated with overall loss of 7q had a significantly less successful induction outcome, with only 28% achieving remission (P = .02); three of seven patients with t(15;17) died during induction therapy.

Cyclic neutropenia in identical twins.

Cyclic neutropenia developed in identical twin girls. The onset of neutropenia in these children occurred three years apart. Neutrophil cycling diminished, and symptoms decreased in the initially affected twin during a five-year follow-up. Some cases of cyclic neutropenia may be genetically determined; however, the onset and clinical manifestations may be modified by other internal and external factors. There may also be a prodromal period during which neutrophils cycle, but the patient is neither neutropenic nor symptomatic.

Ulcerative eosinophilic granuloma of the tongue. A light- and electron-microscopic study.

Ulcerative eosinophilic granuloma of the tongue simulates histiocytosis X or cancerous lesions, and may be subjected to unnecessary excessive treatment. This case report illustrates its benign, self-limited nature, discussed the differential diagnosis, and postulates its pathogenesis on the basis of light- and electron-microscopic findings.

A trial of ciprofloxacin and metronidazole vs gentamicin and metronidazole for penetrating abdominal trauma.

OBJECTIVES: To determine whether a combination of ciprofloxacin hydrochloride and metronidazole hydrochloride would be as effective or more effective than a combination of gentamicin sulfate and metronidazole hydrochloride for preventing infection in patients with penetrating abdominal trauma, to evaluate the factors associated with increased risk of infection, and to determine the serum peak and trough levels of gentamicin with the dosage regimen of 2.5 mg/kg every 12 hours. DESIGN: Randomized double-blind study. SETTING: Level I trauma center. PATIENTS: Eighty-four patients with penetrating intra-abdominal injuries (gunshot wound, 69; stab wound, 15) thought to require laparotomy. INTERVENTIONS: The patients were randomized during treatment in the emergency department to be given a combination of ciprofloxacin hydrochloride, 400 mg every 12 hours, and metronidazole hydrochloride, 500 mg every 6 hours, or a combination of gentamicin sulfate, 2.5 mg/kg every 12 hours, and metronidazole hydrochloride, 500 mg every 6 hours. RESULTS: Of 68 patients with intra-abdominal injuries who could be observed for at least 48 hours after laparotomy, posttraumatic infections developed in 12 (18%), and nosocomial infections developed in 6 (9%). The incidence of posttraumatic infections in patients who were given gentamicin and metronidazole (5/33 [15%]) was not significantly lower than the incidence in patients who were given ciprofloxacin and metronidazole (7 of 35 [20%]; P=.75). The presence of any infection increased the mean+/-SD length of hospital stay from 8.7+/-3.5 days to 23.3+/-10.9 days and increased the mean+/-SD hospital charges from $24 507+/-$9860 to $104920+/-$49083 (P<.001). Univariate analysis showed the factors most significantly associated with infection were as follows: (1) the use of blood transfusions (P<.001), (2) the penetrating abdominal trauma index of 35 or more (P<.002), (3) injury to the colon requiring a colostomy (P=.004), and (4) a trauma score of less than 12 (P<.02). Multivariate analysis showed the only significant factor was the receipt of blood transfusions (F=10.165; P<.005). CONCLUSIONS: Ciprofloxacin and gentamicin, each in combination with metronidazole, were equivalent in their ability to prevent infections after penetrating abdominal trauma; other factors, especially the receipt of blood transfusions, had much more effect on the incidence of infection. Infection greatly increases the length of hospital stay and hospital charges. The use of an increased dosing regimen of 2.5 mg/kg every 12 hours of gentamicin sulfate was effective at obtaining a therapeutic peak serum concentration.

Clinical and economic effectiveness of an inpatient anticoagulation service.

We conducted a prospective cohort study to evaluate clinical and economic end points achieved by a pharmacist-managed anticoagulation service compared with usual care (50 patients/group). The primary therapeutic end point was the time between starting heparin therapy and surpassing the activated partial thromboplastin time therapeutic threshold. The primary economic end point was the direct variable cost of hospitalization from admission to discharge. No significant differences between groups were noted for the primary therapeutic end point. Total hospital costs were significantly lower for patients receiving pharmacist-managed care than for those receiving usual care ($1594 and $2014, respectively, 1997 dollars, p=0.04). Earlier start of warfarin (p=0.05) and shorter hospital stay (5 and 7 days, p=0.05) were associated with the pharmacist-managed group.

Results in children with local and regional neuroblastoma managed with and without vincristine, cyclophosphamide, and imidazolecarboxamide. A report from the Children's Cancer Study Group.

Members of children's cancer study group designed Study CCG 351 to determine whether three drug chemotherapy improved the survival experience of children with localized neuroblastoma. Patients in stages I-III were treated with surgical removal of the primary tumor and those in stages II and III received radiation therapy to the tumor bed and chemotherapy. Treatment included cyclophosphamide, imidazolecarboxamide, and vincristine given in 5-day pulses each month for 12 courses. The results were compared to those from a previous study, CCG 011, for localized neuroblastoma, in which children were randomized between a treatment regimen that included cyclophosphamide and one with no chemotherapy. There were 133 evaluable patients, subdivided as follows: stages I-26, stages II-74, and stages III-33. The 3-year life-table survival rates by stage of 96, 89 and 50% were not significantly different from the patients in CCG 011 similarly staged who received either no chemotherapy or oral CPM. These data suggest that multiagent chemotherapy, as prescribed, did not improve the outlook for children with locally advanced but nonmetastatic neuroblastoma. The staging criteria employed showed a modest difference in outcome between patients in stages I and II, but a significant poorer survival for stage III as compared to either stage I or II.

Neonatal cystic choristoma in submandibular salivary gland simulating cystic hygroma.

A congenital cystic malformation occurred in the submandibular salivary gland of a neonate. The embryogenesis and differential diagnosis are discussed. Since it seems to be a product of endodermal heterotopic differentiation or entrapment of foregut epithelial rests in the submandibular gland, it is classified as a cystic choristoma.

Chronic myopathy associated with coxsackievirus type A9. A combined electron microscopical and viral isolation study.

Virus-like crystalline structures in human skeletal muscles have been observed by many electron microspists, but no viruses have been isolated and identified in such cases. An 11-year-old girl who had had muscular weakness and physical retardation since early infancy died of pneumonia due to atrophy of diaphragmatic and intercostal muscles. Electron microscopy of these muscles revealed a heavy infiltration of picornavirus-like particles that measured 19 to 23 nm in diameter. Subsequent inoculation of primary human-amnion cells with a sonic-treated suspension of the patient's diaphragmatic muscle induced an enterovirus-like cytopathic effect. The isolate was identified with use of Lim-Benyesh--Meinick enterovirus typing serum pools as coxsackievirus Type A-9. This viral isolation supports the belief that the organized electron-dense particles in human muscle are indeed virions.

Sodium o-iodobenzoate and hemoglobin-oxygen affinity: in vivo effects.

Sodium o-iodobenzoate (OISB) was given intravenously to 15 dogs to test the in vivo effect of this drug on the oxyhemoglobin dissociation curve. Administration of a single dose of 500 mg/kg was followed by an average increase in P50 (PO2 at 50% oxyhemoglobin saturation) of 3.6 mmHg from 26.8 +/- 0.5 to 30.4 +/- 1.8 mmHg (corrected to pH 7.4). This elevation was sustained for 7 days. During intravenous infusions of 200 mg/kg every other day for 3 wk, there was a sustained increase in P50 of 2.6 mmHg from 27.8 +/- 1.1 to 30.4 +/- 0.9 mmHg. All dogs survived the experiment and no ill effects of the drug were noted. An increase in serum lactate and pyruvate occurred in all animals following acute or chronic exposure to the drug. There was no significant change in whole blood pH, 2,3-diphosphoglycerate concentrations, intracellular pH, or serum total phosphate. Multiple infusions of sodium cyanate (50 mg/kg per day) reduced P50 by an average of 12.2 +/- 0.3 mmHg. A subsequent single infusion of OISB (500 mg/kg) failed to increase P50. Our preliminary data indicate that pharmacological manipulation of hemoglobin O2 affinity is possible with organic compounds unrelated to erythrocyte metabolism.

Pulmonary fiber embolism and granuloma.

Three infants had pulmonary fiber embolism and granuloma following cardiac catheterization. These complications were traced to the use of nondisposable woven synthetic fiber catheters. The fibrous linings of the catheter may fray and break, and the debris may become disseminated during angiography to the lungs to form emboli and intravascular and extravascular granulomas.

Nephroblastoma (Wilms tumor): tubule density and prognosis.

Relative differences in tubules density of the primary tumors have been suggested to be prognostically useful in nephroblastoma (Wilms tumor). Forty cases from our institution were retrospectively graded according to tubule density. There were significant differences in disease-free survivals between histologic grades. When compared to other clinical and pathologic staging criteria, tubule density was not more useful prognostically than the staging systems tested. However, when used in conjunction with clinical or pathologic stage, tumor grade improved prognostic sensitivity. Regardless of grade or stage, patients less than 24-months-old at diagnosis had better disease-free survival.

Reye syndrome. A correlated electron-microscopic, viral, and biochemical observation.

Liver biopsy specimens of two patients with Reye syndrome were examined for ultrastructural features, viral isolation, and urea-cycle enzyme activity. Concurrent presence of herpes-like virus and myxovirus/paramyxovirus was demonstrated by electron microscopy, and viral infections were confirmed by isolation or serologic tests. A concomitant hepatic ornithine transcarbamoylase deficiency was also noted. The pathogenesis in these instances seems to consist of an initial synergistic insult on the liver by mixed types of viruses and subsequent breakdown of urea cycle, Krebs cycle, and possible other hepatic functions. An exodus of glycogen granules into the hepatic spaces of Disse and sinusoids suggests that the viruses have injured the plasma membranes as well as the mitochondria of hepatocytes. Since Kapila et al reported similar disorders five years before Reye et al, the name of Kapila-Reye disease is suggested.

Improved remission induction rate with D-ZAPO but unimproved remission duration with addition of immunotherapy to chemotherapy in previously untreated children with ANLL.

In 163 children with acute nonlymphocytic leukemia (ANLL), a D-ZAPO induction program consisting of daunomycin, 5-azacytidine, cytosine arabinoside, prednisone, and vincristine resulted in a remission rate of 71.8%. Immunologic therapy was employed during maintenance with the aim of prolonging remission and improving survival. The administration of immunotherapy consisting of a mixture of bacillus Calmette-Guérin (BCG) and allogenic acute myelomonocytic leukemic cells injected intradermally on day 14 of each of the first three monthly cycles of 6-thioguanine for ten days, 5-azacytidine and cytosine arabinoside for four days, and vincristine for one day did not improve remission duration or survival compared to that due to chemotherapy alone. Important prognostic factors identified in this study included a remission induction rate significantly better for females than males (P = 0.04), for children between the ages of 5 and 10 years compared to those greater than this age group (P = 0.01), and a prolonged remission duration (P = 0.04), and survival (P less than 0.01) for patients with initial white blood counts of less than 20 x 10(9)/liter.

Increased survival in childhood acute nonlymphocytic leukemia after treatment with prednisone, cytosine arabinoside, 6-thioguanine, cyclophosphamide, and oncovin (PATCO) combination chemotherapy.

One hundred-sixty-three children with acute nonlymphocytic leukemia (ANLL) were treated with a multiple-drug induction program (PATCO) consisting of prednisone (PDN), cytosine arabinoside ((Ara-C), 6-thioguanine (6-TG), cyclophosphamide (CPM), and Oncovin (VCR). Ninety-six, 59%, obtained a remission. Remission was maintained with daily 6-TG and four-day pulses of Ara-C and CPM with a single dose of VCR every 28 days. The median duration of remission was 11.5 months. Certain prognostic factors affected induction rate and remission duration. Initial white blood count (WBC) was a significant factor in achieving a remission, whereas age, sex, and type of ANLL had no effect. Initial WBC, age, and sex had a significant effect on remission duration, but type of ANLL had no effect. Relapsing patients were treated with daunomycin and 5-azacytidine. The reinduction rate was 53% with a median second remission duration of 190 days. Overall survival for the 163 patients is 55.4% at 12 months, 31.5% at 24 months, 21.4% at 36 months, and 19% at 48 months.