The response of Ewing's sarcoma to sequential cyclophosphamide and adriamycin induction therapy.

Twenty-four consecutive patients with Ewing's sarcoma were treated in a protocol designed to deliver induction chemotherapy with postinduction surgical-pathologic evaluation of the primary tumor site. This was followed by delayed radiotherapy, the dose and port of which was dependent on the response to induction chemotherapy. All patients received 5 courses of sequential cyclophosphamide and adriamycin during the 3-mo induction period. Nineteen of 23 evaluable patients had no gross residual tumor following this therapy. Of the remaining 4, 2 had complete surgical excision of residual gross disease. Of the 22 patients who were free of gross tumor following induction chemotherapy and surgery, 5 received no radiotherapy, 16 received moderate-dose limited port radiotherapy (3000-3500 R), and 1 received high-dose limited port radiotherapy (5000 R). All 14 patients with localized disease attained remission and are surviving 9-41+ mo (median 21+) with 2 local recurrences occurring after 10 and 33 mo of remission. Of the 10 patients presenting with metastatic disease, 8 attained complete remission with 4 of the 8 remaining disease-free 12-34+ mo from diagnosis. This study indicates that Ewing's sarcoma is very sensitive to moderate-dose 2 drug chemotherapy of low toxicity and that it is possible to delay radiotherapy and any extensive surgical procedure until remission is induced.

Serial cranial computed-tomography scans in children with leukemia given two different forms of central nervous system therapy.

Cranial computed tomography (CT) was used to estimate the frequency and permanence of brain abnormalities in 108 consecutive children with acute lymphoblastic leukemia (ALL). Fifty-five patients received cranial irradiation (1,800 rad) with intrathecal methotrexate (RT group) and 53 patients received intravenous and intrathecal methotrexate without irradiation (IVIT group). Continuation treatment included sequential drug pairs for the RT group and periodic IVIT methotrexate for the other group. After 12 to 24 months of serial evaluation, five (9%) of the 55 patients in the RT group have had CT scan abnormalities, compared to 10 (19%) of 52 in the IVIT group (p = 0.171). Fourteen of the 15 patients with CT scan abnormalities had focal or diffuse white-matter hypodensity; these have reverted to normal in most cases, reflecting a dynamic process. While such CT findings are of concern and may be an early indicator of central nervous system toxicity, this remains to be proven. Therapy should not be altered on the basis of abnormal CT scans alone but in the context of the entire clinical situation.

Ultrastructure of malignant histiocytoma arising in the acromion.

The ultrastructural features of a malignant histiocytoma of the acromial process of the scapula were studied. Material was obtained from two surgical biopsy specimens and an amputation specimen from the tumor. Cells possessing characteristics of histiocytes, fibroblasts, xanthoma cells, and multinucleated giant cells were present throughout the tumor. Smaller numbers of undifferentiated cells and lymphocytes were also observed. Intimate cytoplasmic interdigitations between adjacent tumor cells were found, and instances of degenerating intracytoplasmic cells, possibly representing phagocytosis, were observed. Specimens stained with periodic acid-Schiff reagent with and without exposure to diastase, examined by light microscopy, showed that numerous cells contained phagocytized material consisting of degenerating cells rather than cytoplasmic glycogen. Intraumor lymphocytes apparently represented an inflammatory reaction to the tumor. The tumor giant cells and xanthoma cells were probably modified histiocytes. Results of the study were compared with previous reports of ultrastructural studies of malignant histiocytoma of soft tissues. Fundamental similarities between such studies and this one suggested that the progenitor cell is a histiocyte, whether arising in bone or in soft tissues, and that the progenitor cell is capable of differentiation in both histiocytic and fibroblastic directions.

Pharmacokinetics of sustained serum methotrexate concentrations secondary to gastrointestinal obstruction.

A physiological pharmacokinetic model for methotrexate was refined and used to simulate serum methotrexate concentrations after high dose (5000 mg/m2) intravenous infusions with fixed normal values for all model parameters except the GI transit rate. There was good agreement between simulated and measured values when model simulations with the normal GI transit rate were compared to values measured following 109 doses administered to 27 patients with normal GI function. When model simulations were performed using GI transit rates representing 75, 50 and 10% of normal, there was a marked prolongation of the terminal serum methotrexate half-life, which was directly related to the reduction in the transit rate. When simulations were performed with GI transit reduced by 50%, the maximum amount of methotrexate in the GI lumen was 25% higher and occurred 4 hr later. Model simulations of serum methotrexate concentrations, using a GI transit rate reduced by 50%, were also in good agreement with serum concentrations measured in two patients with partial GI obstruction. These data establish a pharmacokinetic basis for previous clinical observations indicating sustained serum methotrexate concentrations in patients with GI obstructions and exemplify the utility of physiological pharmacokinetic models in assessing the potential effects of clinical variables on drug disposition.

Statistical Analysis of On-Road Particulate Matter Emissions from Diesel Vehicles.

During 1996 and 1997, a number of light-and heavy-duty diesel vehicles were recruited in the Denver metropolitan area and subjected to emissions testing, principally for the purposes of assessing on-road particulate emissions. Little if any comparable data had been collected at altitude, particularly from heavy-duty vehicles. When these data were statistically examined using the technique of analysis of variance, they were shown both to exceed the federal standards, on average, and to be highly variable. These findings suggest that typically reported average values of vehicular PM emissions are not sufficient to be used, by themselves, to estimate contamination levels and associated public health risk. The situation is exacerbated in studies involving small numbers of vehicles, which is typical when diesel vehicles are involved, since not all sources of variation can be simultaneously controlled. Precise knowledge of the amount of particulates emitted by diesel vehicles in actual daily use is important because of present government strategies designed to promote the use of diesel as a transportation fuel.

Treatment strategy for nodular renal blastema and nephroblastomatosis associated with Wilms' tumor.

Nodular renal blastema and nephroblastomatosis were present in 8 of 118 patients (6.8%) with Wilms' tumor. Five of these 8 patients (63%) had bilateral Wilms' tumors. Two had hemihypertrophy. Preoperative renal angiograms were accurate in detecting these metanephric anomalies. The surgical approach consisted of removal of the most diseased kidney and biopsy for diffuse tumors and wedge resections for localized tumors for the remaining kidney. Postoperatively, radiation was administered when tumor extended outside the kidney. Chemotherapy consisted of vincristine and dactinomycin for 18 mo and adriamycin for 6 mo. This method of management resulted in tumor-free survival of these 8 patients for 1--44 mo (median 24 mo). Nodular renal blastema and nephroblastomatosis may possibly develop into Wilms' tumor. All of these three conditions respond to surgery, chemotherapy, and radiation. When a Wilms' tumor is encountered, it is better to explore and possibly biopsy the opposite kidney. There is a place for second-look laparotomy in this spectrum of congenital anomalies.

Prevalence of gastrointestinal parasitism in Oklahoma swine.

The prevalence of swine gastrointestinal parasites was determined from all listed large swine operations (28) and a geographically representative sample (70) of the population of small hog farm operations in Oklahoma. Fecal samples (n = 975) were collected from 98 farms. From the 98 farms, parasites were recovered in pig feces as follows: Ascaris, 53.0%, strongyles, 53.1%, Trichuris, 35.7%, spirurids, 6.1%, Strongyloides, 19.4%, coccidia, 57.1%, and Balantidium, 55.1%. A higher percentage (16.5%) of hogs maintained on cement floors were positive for Ascaris than were those on either dirt lots (11.9%) or slatted floors (9.9%), but pigs on dirt lots were more often positive with a higher percentage of coccidia (21.0%) than those on either cement or slatted floors (8.5% and 6.0%, respectively). Prevalence of Trichuris was essentially the same (6.8% to 11.3%) in hogs from all 3 management practices.

Cost-effectiveness of cervical cytologic examination during pregnancy.

BACKGROUND: We undertook a study to determine the cost-effectiveness of performing routine cervical cytologic examination during pregnancy. METHODS: The costs generated by doing routine prenatal cervical cytologic examination were calculated based on chart review in a family practice setting. A consecutive sample of 523 patients giving birth during 1990 was used. Analysis was done on 423 of those patients with prenatal Papanicolaou smear results recorded. Cost savings from detection of curable disease and utility of the test in terms of well-years saved were calculated from published statistics using a single-step Markov process to model the population at risk. RESULTS: For patients of all ages using a discount rate of 5 percent, the cost generated by prenatal cervical cytologic examination was $146,400 per well-year of life saved. Age stratification showed cost per well-year to range from $321,600 for patients aged 15 to 19 years to $48,800 for those aged 35 to 39 years. CONCLUSIONS: Routine prenatal cervical cytologic examination is significantly less cost-effective than the most commonly done medical procedures. If medical funding is limited, elimination of this test should be considered for women with normal findings on cervical cytologic examinations within the previous 2 to 3 years.

Unacceptable variability of hemoglobin estimation on samples obtained from ear punctures.

Sampling techniques were studied for the determination of the hemoglobin in volunteer blood donors. First, finger, ear, and venous samples were collected from 50 volunteers. Then five volunteers were monitored for a three-day period and finger, ear, and venous samples were collected daily. Thirdly, microhematocrits were done on the postdonation EDTA samples of 500 donors who had been screened using ear puncture copper sulfate hemoglobin estimations. Fourth, 25,437 donations were followed up to see whether capillary sampling techniques affected the rate of donor deferral. And finally, the ear sampling technique was varied using vigorous rubbing and manipulation to see if there was abnormal circulation that would affect the hematocrit results from capillary blood from the ear. We found that the microhematocrits averaged 7 per cent higher from blood obtained from ear puncture than from either finger puncture or venous puncture. Microhematocrits obtained from blood obtained by ear puncture were less accurate and less precise than blood from finger punctures. Finger puncture samples exclude approximately 6 per cent more donors than does blood from ear punctures.

Use of infusion pump for intravenous enhanced computed tomography.

For enhanced computed tomography, rapid injections through small bore needles can be easily accomplished utilizing an infusion pump. A reduction in radiation exposure to medical personnel is an associated benefit.

Normal computed tomograms of the brain in osteosarcoma patients treated with high-dose methotrexate.

Eighteen patients with osteosarcoma, most of whom were adolescents, were examined for abnormalities of the brain by use of computed axial tomography. These studies were performed at 15-60 months (median 47 months) after the completion of adjuvant chemotherapy, which included high-dose methotrexate, cyclophosphamide, and Adriamycin. No abnormalities were found. The results of this study, together with the absence of brain lesions in published reports in children receiving high-dose methotrexate but no cranial irradiation, indicate that delayed neurotoxicity is not a major complication of this form of therapy in older children.

The value of computerized tomography as a routine follow-up procedure for patients with Wilms' tumor.

We performed routine computerized tomography (CT) of the chest and abdomen on patients treated for Wilms' tumor and reviewed the records of all patients who relapsed (10 patients) and 43 additional patients followed for at least 1 year. Routine chest radiographs and abdominal ultrasounds were compared with 210 CT examinations (107 chest and 103 abdomen). CT examinations were obtained at 6 months for stage I (13 patients) and at 3, 8, and 15 months for stages II, III, and IV (40 patients). Of the 10 patients who relapsed, only 2 were documented by CT scan in the absence of clinical symptomatology and presence of normal radiographs and ultrasound. Eight relapses were diagnosed by physical examination, chest radiograph, or ultrasound and confirmed by CT scan. Questionably abnormal CT scans were obtained in 7 patients, only 1 of whom eventually relapsed. Since only 2 of 210 routine CT examinations were the the only indicator of relapse, we conclude that the routine use of CT for follow-up in Wilms' tumor is not warranted.

Percutaneous transthoracic needle aspiration of the lung. Diagnosing Pneumocystis carinii pneumonitis.

Percutaneous transthoracic needle aspiration was performed on 228 occasions to obtain lung specimens from 202 patients with suspected Pneumocystis carinii pneumonitis. In 121 patients the diagnosis was established by identifying P carinii organisms in lung aspirates. Six patients whose aspirates did not contain P carinii were found to have the organism at autopsy. Findings from toluidine blue O and Gomori methenamine silver nitrate stains were equally satisfactory for detecting P carinii, but the percentage of specific diagnosis was higher when specimens were stained with both. Pneumothorax that required a thoracotomy tube occurred in 39 patients. Other infectious agents, either bacteria or fungi, were found in only four patients. Percutaneous pulmonary needle aspiration--when performed under fluoroscopic guidance--is a rapid and effective method for the diagnosis of P carinii pneumonitis.

Behavior modification in pediatric hemodialysis.

This article reports the results of a behavior modification approach for managing disruptive and noncompliant behaviors in four male hemodialysis patients ranging in age from 10 to 16 years. Each patient demonstrated some improvement in either behavior or health status during the intervention and 76.7% of available token reinforcers were earned. The intervention was inexpensive and well-accepted by the patients, families, and staff. Guidelines for the planning, implementation, and evaluation of such interventions are presented.

Progression of methotrexate-induced leukoencephalopathy in children with leukemia.

From 1972-1974, 228 children began treatment for acute lymphocytic leukemia and were prospectively assessed for neurologic complications. After CNS irradiation (2,400 rad) and intrathecal methotrexate (MTX), they received weekly intravenous maintenance therapy with MTX alone (40-60 mg/m2; 20 patients) or MTX (10-30 mg/m2) with other drugs (208 patients). Signs of leukoencephalopathy appeared in 11 children (nine without CNS leukemia) after 4-15 months of IV MTX alone, and included lethargy, seizures, spasticity, paresis, drooling, and dementia. Before or during the clinical onset, EEG frequencies slowed (all ten patients tested). Radionuclide scans showed periventricular accumulation of 99mTc (9/11 patients) and remained abnormal for greater than or equal to six months in eight patients. Cranial computed tomograms or neuropathology findings (five patients each) demonstrated leukoencephalopathy (nine patients) and radiation-related microangiopathy (ten patients). Severe neurologic and neuropsychologic dysfunctions were present in four long-term survivors.