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Biomedical subjects

M P Sullivan

Publications and source records attributed to M P Sullivan.

At least 73 records · Page 4Linked to original sources

A morphologic study of childhood lymphoma of the diffuse "histiocytic" type. The Pediatric Oncology Group experience.

Of 227 cases of pediatric non-Hodgkin's lymphoma with adequate histopathologic material for review, 72 (32%) were classified as diffuse "histiocytic" lymphoma (DHL). These cases were further divided into different morphologic subtypes according to the Lukes-Collins classification, and the National Cancer Institute Working Formulation, to ascertain whether there were any significant prognostic differences among the different subtypes. The results of our study showed that 40 patients were classified as immunoblastic lymphomas, and 32 were called large follicular center cell (FCC) tumors. Of the 40 patients with immunoblastic histology, 19 had morphologic features of the clear cell type and were interpreted as consistent with T-immunoblastic lymphomas; an additional two had polymorphous features also consistent with T-cell type: 17 had plasmacytoid features, and were morphologically classified as B-immunoblastic lymphomas; two could not be subtyped. Of the 32 patients with morphologic features of FCC lymphomas, 29 were classified as large noncleaved type, and three as large cleaved type. A clinicopathologic analysis showed that 90% of the patients obtained complete remission, and there were no significant differences in complete remission rate among the different morphologic subtypes of DHL. The estimated five year disease-free survival for all patients was over 70%, with no failure after the second year; and there were no significant differences in the disease-free survival among the different subtypes. The only clinical differences that we found, were that patients with lymphomas of FCC (large noncleaved) type were younger (P = 0.01); had less nodal involvement (P = 0.03); and had more organ involvement (P less than 0.01). We conclude that the morphologic subclassification of DHL in children currently has limited clinical prognostic significance.

Adolescent↗

Mediastinal mass following chemotherapeutic treatment of Hodgkin's disease: recurrent tumor or thymic hyperplasia?

Hyperplasia of the thymus is a normal physiologic response in infants and children during recovery from life-threatening illness. New, recurrent, or residual mediastinal masses in children treated for malignant disease present a diagnostic dilemma. Are these masses recurrent disease or simply normal reactive thymic hyperplasia? Our experience from 1979 to 1986 includes 14 children aged 1 to 17 years (mean 7.4 years) who were identified with new or recurrent mediastinal masses during or after chemotherapeutic treatment for malignant disease (lymphoma 9, Wilms tumor 2, leukemia 1, osteosarcoma 1, malignant teratoma 1). The mediastinal masses were treated by a variety of methods depending on the attending physician's preference (close observation 2, oral steroids 5, steroids and subsequent biopsy 1, open biopsy 6). Chest roentgenograms of "observation only" patients have showed stable mediastinal changes without clinical evidence of recurrent disease. Patients treated with steroids showed resolution of the mediastinal masses in 48 hours to seven days, without recurrence. Patients undergoing open biopsy showed only thymic hyperplasia and/or lymph nodes. We suggest a stepwise approach to evaluation of these patients. Mediastinal masses occurring during, or shortly following, chemotherapeutic treatments of malignant disease should first be treated with oral prednisone (60 mg/m2/d x 7 to 10 d). If the patient shows a complete or partial resolution, then follow-up includes frequent chest roentgenograms and/or a second course of steroids. If the mass fails to respond to steroids, or enlarges, then open biopsy through a minithoractomy will clarify the diagnosis. Follow-up of our patients is from 3 months to 7 1/2 years (mean 5 years).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Verbal and perceptual analogical reasoning and proportional metaphor comprehension in young children.

In contrast to the common assumption that young children have little or no ability to reason by analogy or to comprehend proportional metaphors, the present study demonstrated that children as young as age 5 years have an emerging ability to solve both verbal and perceptual proportional analogy problems and to detect the meanings of proportional metaphoric sentences. These results were largely because the experimental tasks were designed to minimize the number of factors that would restrict the performance of young children. The results indicated that the years between 5 and 7 mark a steady improvement in analogical reasoning and proportional metaphor comprehension, but that children ages 5, 6, and 7 display a wide-ranging ability in these areas. It was also found that perceptual analogical reasoning was statistically related to verbal analogical reasoning and to proportional metaphor comprehension, and that perceptual analogical reasoning and proportional metaphor comprehension were both statistically related to receptive vocabulary development.

Child↗

Hodgkin's disease in children.

Hodgkin's disease may now be managed with several different regimens with the expectation of curing approximately 90 per cent of patients. Radiotherapy alone achieves this cure rate only in unilateral high cervical or inguinal stage 1 presentations. With all other presentations, radiotherapy requires the addition of chemotherapy to sustain the 90 per cent cure level. Combined modality regimens offer the patient the advantage of reduced doses of each modality in terms of number of Gy and courses of chemotherapy. The contribution of the staging laparotomy to combination therapy is now being questioned. This issue becomes pressing as imaging of the lymphatic system and commonly involved extranodal sites of disease is improved by computed tomography, magnetic resonance, and ultrasound technology. Only the spleen escapes adequate examination. The failure of imaging techniques to adequately determine the status of the spleen is compensated by the chemotherapy sensitivity of splenic disease, as often demonstrated in the treatment of patients with stage IV disease. Staging laparotomy for preadolescent children should be done on special indications, because splenectomy confers a life-long (50 years or more) threat of overwhelming infection despite administration of pneumococcal vaccine and the use of oral penicillin prophylaxis. The use of radiotherapy in a dose range that inhibits bone and dental development in immature, preadolescent children can no longer be condoned. Treatment with chemotherapy alone must be considered as the option for preadolescent and younger adolescent children. Radiotherapy in a low dose range (2000 to 2200 cGy) in combination with chemotherapy constitutes a possible alternative treatment. In combined therapy regimens, it appears unnecessary to deliver six full courses of chemotherapy because regimens using three or four courses have demonstrated effectiveness in adults with early stage disease. The selection of the chemotherapy regimen should be made with care so as to eliminate drugs causing sterility in the young male, ovarian dysfunction in females, and second malignant tumors including acute myeloid leukemia (AML). In addition, doxorubicin should be used only in noncardiotoxic cumulative doses. Pretreatment determinations of the cardiac ejection fraction provide some assurance of safety during doxorubicin therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Child↗

Second malignant neoplasm in treated Hodgkin's disease. Report of a patient and scope of the problem.

The condition of a 6-year-old boy was diagnosed as mixed-cellularity Hodgkin's disease that involved the right side of the neck. Five years after the completion of radiation therapy for the involved area, followed by six courses of chemotherapy with mechlorethamine hydrochloride (nitrogen mustard), vincristine sulfate, procarbazine hydrochloride, and prednisone, he developed cerebral gliosarcoma. Numerous second malignant neoplasms have been reported in adults following treatment for Hodgkin's disease; however, the sequence of events in our patient is a new finding that has not, to our knowledge, been reported previously. While the second malignant tumor may have been induced by prior treatment, direct evidence is lacking.

Antineoplastic Combined Chemotherapy Protocols↗

Postsplenectomy sepsis and other complications following staging laparotomy for Hodgkin's disease in childhood.

This is a survey of 234 pediatric patients in whom staging laparotomy/splenectomy was carried out (1975 to 1981) in the course of the Intergroup Hodgkin's Disease in Childhood Study (IHDCS). Relapse has occurred in 44 of these patients, and 12 have died, 7 secondary to extension of lymphoma, 2 with herpes or pneumocystis infections, 2 with leukemia, and 1 from an unrelated accident. During the period of surveillance (mean 5.5 yr), five episodes of bacterial sepsis (positive blood cultures) have occurred, including two due to Streptococcus pneumoniae; and three, to Hemophilus influenzae. The former occurred in the small group of patients in this series who had not received the prescribed pneumococcal vaccination. No fatalities were associated with these septic episodes. Intestinal obstruction secondary to adhesions (benign) occurred in eight patients and was managed without intestinal resection or mortality. One patient required operative release of an obstructed ureter following laparotomy, and one, oophorectomy for an infarcted (transposed) ovary.

Adolescent↗

Pediatric Oncology Group experience with modified LSA2-L2 therapy in 107 children with non-Hodgkin's lymphoma (Burkitt's lymphoma excluded).

From September 1976 to August 1979 the Pediatric Oncology Group accessed 145 children to study the effectiveness of modified LSA2-L2 therapy for the treatment of non-Hodgkin's lymphoma (NHL). Burkitt's lymphoma patients were ineligible; E-rosette-positive patients with greater than or equal to 25% blasts in the marrow entered after February 1977 were reported separately. Radiotherapy could be used to treat patients with compressive mediastinal disease at diagnosis and was prescribed for those with residual abdominal disease as demonstrated by second-look surgery on completion of induction chemotherapy. Confirmation of diagnosis by the Pathology Panel and Repository Center for Lymphoma Clinical Trials was mandatory. Diagnostic tissues of 131 patients were reviewed. Among 107 evaluable patients, 91 (85%) achieved complete remission. Differences in response rates among the three major histologic groups (lymphoblastic, undifferentiated, and large cell) were of statistical significance, with response being poorest for diffuse undifferentiated lymphoma (P = 0.03). Failure-free survival did not differ significantly for the three major histologic diagnoses. While response rate was lowest for Murphy Stage III patients (79%), the differences among the stages were not significant. Stage was not a significant prognostic factor for failure-free survival (P = 0.08). The number of patients still at risk and the Kaplan-Meier estimate of percentage of patients remaining at risk after 3 years is: Stage I, 8 (100%); Stage II, 10 (67%); Stage III, 28 (57%); Stage IV, 6 (39%); and greater than 25% blasts, 1 (13%). Stage III failure curves for lymphoblastic disease show continuing stepwise failure through 3 years. Among patients with diffuse large cell and undifferentiated disease, most failures occurred by 8 months. M1 and M2 levels of marrow involvement were not prognostic among children with lymphoblastic disease. The presence of a mediastinal mass was a significant factor contributing to failure in children with lymphoblastic disease without marrow involvement. Leucocytosis greater than 10,000/1, was a significant (P = less than 0.001) factor predicting failure-free survival for patients with large cell lymphoma. The delivery of radiotherapy was not a significant factor in achieving remission. No consistent benefit resulted from using radiotherapy to treat postinduction residual disease demonstrated on second-look exploration. The LSA2-L2 regimen was associated with considerable toxicity, severe or worse in 77% and life-threatening to 40% of these patients. Four died of toxicity. However, therapy was given more easily and safely as investigator experience increased.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Liposomal amphotericin B for the treatment of systemic fungal infections in patients with cancer: a preliminary study.

Twelve patients with hematologic malignancies complicated by fungal infections were treated with liposomal amphotericin B (L-AmpB). Nine patients were granulocytopenic; the three additional patients with normal granulocyte counts were immunosuppressed. All patients had biopsy findings or cultural evidence of the progression of their fungal infection while being treated with conventional amphotericin B. Doses of 0.8-1.0 mg/kg of L-AmpB were administered intravenously every 24-72 hr. Three patients had a complete remission, five had a partial remission, and four showed no improvements. A total of 161 doses of L-AmpB were administered. Fever and chills occurred on seven occasions. No hematologic or blood chemistry abnormalities related to L-AmpB treatment were observed.

Adolescent↗

Curability of Burkitt's lymphoma with high-dose cyclophosphamide-high-dose methotrexate therapy and intrathecal chemoprophylaxis.

Twenty-four children with Burkitt's lymphoma were treated beginning May 1976 with a regimen alternating high doses of cyclophosphamide and methotrexate in induction and consolidation; only high doses of methotrexate were used in the maintenance phase. Throughout therapy, which was planned for 54 weeks, intrathecal chemoprophylaxis using methotrexate, cytosine arabinoside, and hydrocortisone was coordinated with the high-dose methotrexate infusion therapy to provide CNS chemoprophylaxis that maintained therapeutic methotrexate spinal fluid levels (greater than 10(-6) mol/L) for approximately 60 hours. Twenty-two (92%) of the 24 children attained complete remission; two (8.3%) patients attained only partial remission, failing therapy. Two children died of infection while in complete remission; two children relapsed on therapy. Actual survival is 75%; the median follow-up time is 38+ months (range, 1 1/2+ to 84+ months). Relapses correlated with Murphy disease stage as follows: stage I--0/3, stage II--2/7, stage III--2/10, and stage IV--0/2. Serious side effects and toxicities of chemotherapy occurred in ten patients (metabolic disturbances after rapid tumor lysis, two; infectious and/or febrile episodes following cyclophosphamide therapy, three; methotrexate side effects, four; and complications of intrathecal therapy, one). Results of this therapy are similar to those of the best regimens that have been reported. Treatment has been adapted for use in Burkitt's lymphoma by the Pediatric Oncology Group; the responsiveness of other B cell lymphomas of childhood to this treatment is also being determined.

Adolescent↗

Impact of the timing of triple intrathecal therapy on remission induction in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study.

Five weekly doses of triple intrathecal (IT) chemotherapy (methotrexate, hydrocortisone, cytosine arabinoside) starting on day 1 of treatment were added to systemic induction therapy in a regimen (Arm 3) that was compared to three other regimens (Arms 1, 2, and 4) in which central nervous system (CNS) prophylaxis was initiated after complete marrow remission (CR) was attained. The CR rate for Arm 3 was only 83% as compared to 91-92% for other Arms. The lower CR rate was the result of a significantly higher death rate during induction for patients receiving early CNS prophylaxis (10.6 vs 0.9-3.5%). These differences were only observed in high risk patients as defined in the study. The early death rate was especially high (30%) in Arm 3 for children who were less than 2 years of age. Infection was the primary cause of morbidity and mortality. Severe infection following the initiation of induction therapy was found in 16.7% of patients on Arm 3 vs 1.8-6% on other regimens. Immediate triple IT chemoprophylaxis during induction therapy of acute lymphoblastic leukemia as used in this study appears to be associated with increased susceptibility to infection and this form of CNS prophylaxis has increased hazards of morbidity and mortality in infants and other high risk patients.

Age Factors↗

Complications related to 234 staging laparotomies performed in the Intergroup Hodgkin's Disease in Childhood study.

This is a study of 234 children and young adult patients entered in the Intergroup Hodgkin's Disease in Childhood (stage I-II) Study from November 1975 to June 1981 and followed for a mean of 3.8 years after laparotomy. All patients had a staging laparotomy with total splenectomy, liver biopsy, and sampling of abdominal lymph node groups. Four patients (1.7%) have had documented sepsis, and three have had possible sepsis. There has been no sepsis-related death. Intestinal obstruction requiring operation was noted in four patients (no intestinal resection required). Urgent operation was necessary in two patients, one with ureteral obstruction and one with ovarian torsion, following a repositioning procedure, neither of these patients died. Organisms in the four patients with positive blood cultures were Streptococcus pneumoniae (two) and Haemophilus influenzae (two). Of the 234 patients in the study, 194 (83%) had received polyvalent pneumococcal vaccine, and 174 (74%) were taking prophylactic antibiotics. One of the two patients with pneumococcal sepsis had not been vaccinated, and the second was vaccinated only during radiotherapy. Only one of the four patients with positive blood cultures was on a prophylactic antibiotic treatment regimen at the time of the septic episode. The liabilities in employing laparotomy-splenectomy for the evaluation of pediatric patients with Hodgkin's disease include both general surgical complications and an increase in the risk of hyperacute infection, specifically related to encapsulated species. The latter appears to be modified to a major degree by current prophylactic measures or therapy.

Adolescent↗

Dental and maxillofacial abnormalities in long-term survivors of childhood cancer: effects of treatment with chemotherapy and radiation to the head and neck.

Sixty-eight long-term survivors of childhood cancer were evaluated for dental and maxillofacial abnormalities. Forty-five patients had received maxillofacial radiation for lymphoma, leukemia, rhabdomyosarcoma, and miscellaneous tumors. Forty-three of the 45 patients and the remaining 23 who had not received maxillofacial radiation also received chemotherapy. Dental and maxillofacial abnormalities were detected in 37 of the 45 (82%) radiated patients. Dental abnormalities comprised foreshortening and blunting of roots, incomplete calcification, premature closure of apices, delayed or arrested tooth development, and caries. Maxillofacial abnormalities comprised trismus, abnormal occlusal relationships, and facial deformities. The abnormalities were more severe in those patients who received radiation at an earlier age and at higher dosages. Possible chemotherapeutic effects in five of 23 patients who received treatment for tumors located outside the head and neck region comprised acquired amelogenesis imperfecta, microdontia of bicuspid teeth, and a tendency toward thinning of roots with an enlarged pulp chamber. Dental and maxillofacial abnormalities should be recognized as a major consequence of maxillofacial radiation in long-term survivors of childhood cancer, and attempts to minimize or eliminate such sequelae should involve an effective interaction between radiation therapists, and medical and dental oncologists.

Adolescent↗

Radiation induced osteochondroma in long-term survivors of childhood cancer.

The records of 200 long term survivors of childhood cancer where reviewed. Radiation induced osteochondromata were detected in 12 patients (6%). Radiation had been administered in doses ranging from 1250 R (approximately 1500 rad) to 5500 rad between the ages of 8 months and 11 1/2 years. Radiation-induced osteochrondromata were detected 3 to 13 1/2 years later, with a median of 5 years. The osteochrondomata were single in 7 patients and multiple (2-4) in 5. Two occurred at sites of previous thoracotomy. Factors related to radiation induced osteochondromata are discussed.

Bone Neoplasms↗

Compliance with staging laparotomy in the Intergroup Hodgkin's Disease in Children Study: a preliminary report.

The intergroup Hodgkin's Disease in Children Study was designed to determine minimum effective treatment for stage I and II Hodgkin's disease in children up to 18 years of age. Accurate staging of the disease was therefore critical. The number of cases in which the surgeons adhered to the principles and details of the protocol staging laparotomy were less than anticipated during the first 3 years of the study. Improvement in protocol compliance increased as the study progressed. The educational efforts by cooperative groups are credited with initiating this improvement.

Adolescent↗

Target location and visual feedback as variables determining accuracy of aiming movements.

The accuracy of a long aiming movement was studied as a function of whether it was performed toward or away from the midline of the subject's body in the presence or absence of visual feedback. 30 right-handed, male university students (19-26 yr.) served as subjects. With movement distance and duration controlled, the mean percentage of error was 6.34% less for movements made toward the body's midline than for those performed away from the midline. The mean percentage of error was also 48% less in the presence of visual feedback than in its absence. However, contrary to our expectation, movements executed toward the body's midline were not appreciably less disrupted in the absence of visual feedback than movements performed away from the midline.

Adult↗

Pelvic and ovarian extramedullary leukemic relapse in young girls: a report of four cases and review of the literature.

Currently attention is focused on the testicle as a site of leukemic relapse. Leukemic involvement of the ovary has been described in several autopsy series with an incidence of 11-50% in patients with bone marrow relapse, but has rarely been reported during the clinical course of leukemia. In this report, four girls with childhood acute lymphocyte leukemia (ALL) who relapsed with a pelvic mass are presented. Three had marked ovarian infiltrates and the fourth had a presacral mass without ovarian disease. Involvement was also present in abdominal and pelvic lymph nodes, mesentery, omentum, and serosal surfaces. Two patients had infiltrates of the fallopian tubes and one had uterine involvement. Two patients had central nervous system disease and one patient has renal involvement at the time of relapse. Relapse occurred late in the course of disease. All patients had been in complete continuous remission prior to relapse. Retreatment was instituted in all patients and follow-up ranges from 18-135 months from the time of pelvic relapse. All patients have maintained continuous bone marrow remission from the time of initial diagnosis, and one patient died 18 months after ovarian relapse with significant extramedullary disease but no marrow involvement. This represents the first series of pelvic extramedullary leukemic relapse in females, an area of involvement that may be encountered more frequently in the future.

Adult↗

Use of cytosar in pediatric acute myelocytic leukemia and leukemic meningitis.

For children with acute myelocytic leukemia, 5-day courses of Cytosar in combination with cyclophosphamide (with or without vincristine sulfate and prednisone) has shown excellent, age related results in relapse patients. The regimen known as Mini-COAP has been incorporated into front-line studies. Cytosar given intrathecally in combination with methotrexate has produced superior results in treating meningeal disease in the African presentation of Burkitt disease. This "synchronizing" technique has been incorporated into a high Cytoxan-high methotrexate regimen with coordinated intrathecal therapy with good results. Triple (Cytosar, methotrexate, and hydrocortisone) intrathecal prophylaxis is now demonstrated to have equivalent effectiveness to conventional CNS prophylaxis employing radiotherapy 2400 R and 5 doses of intrathecal methotrexate.

Age Factors↗