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Biomedical subjects

A A Green

Publications and source records attributed to A A Green.

At least 19 recordsLinked to original sources
PubMed2001

Parity violation in proton-proton scattering at 221 MeV.

The parity-violating longitudinal analyzing power, A(z), has been measured in pvectorp elastic scattering at an incident proton energy of 221 MeV. The result obtained is A(z) = [0.84+/-0.29(stat)+/-0.17(syst)]x10(-7). This experiment is unique in that it selects a single parity violating transition amplitude (3P2 - 1D2) and consequently directly constrains the weak meson-nucleon coupling constant h(pp)(rho). When this result is taken together with the existing pvectorp parity violation data, the weak meson-nucleon coupling constants h(pp)(rho) and h(pp)(omega) can, for the first time, both be determined.

Journal Article↗
PubMed2001

Effect of propionyl-L-carnitine on exercise performance in peripheral arterial disease.

BACKGROUND: Supplementation with propionyl-L-carnitine (PLC) may be of use in improving the exercise capacity of people with peripheral arterial disease. METHODS: After a 2-wk exercise familiarization phase, seven subjects displaying intermittent claudication were studied over a 12-wk period consisting of three 4-wk phases, baseline (B), supplementation (S), and placebo (P). PLC was supplemented at 2 g x d(-1), and subjects were blinded to the order of supplementation. Unilateral calf strength and endurance were assessed weekly. Walking performance was assessed at the end of each phase using an incremental protocol, during which respiratory gases were collected. RESULTS: Although there was not a significant increase in maximal walking time ( approximately 14%) in the whole group, walking time improved to a greater extent than the individual baseline coefficient of variation in four of the seven subjects. The changes in walking performance were correlated with changes in the respiratory exchange ratio both at steady state (r = 0.59) and maximal exercise (r = 0.79). Muscle strength increased significantly from 695 +/- 198 N to 812 +/- 249 N by the end of S. Changes in calf strength from B to S were modestly related to changes in walking performance (r = 0.56). No improvements in calf endurance were detected throughout the study. CONCLUSIONS: These preliminary data suggest that, in addition to walking performance, muscle strength can be increased in PAD patients after 4 wk of supplementation with propionyl-L-carnitine.

Adult↗
PubMed1997

Treatment of poor-risk neuroblastoma patients with high-dose chemotherapy and autologous peripheral stem cell rescue.

A single institutional pilot study was conducted in which 12 poor-risk neuroblastoma (NB) patients were uniformly treated with multi-agent induction chemotherapy followed by myeloablative consolidation chemotherapy and unpurged peripheral blood stem cell (PBSC) rescue. In addition to using standard criteria for evaluating response to induction chemotherapy, tumor cell contamination of the peripheral blood and/or bone marrow was analyzed in seven patients by immunocytology using a panel of five anti-NB monoclonal antibodies. Seven patients had morphologic evidence of bone marrow disease at the time of diagnosis, and two additional patients had tumor cells detected in bone marrow samples by immunocytology prior to the second cycle of chemotherapy. After three cycles of chemotherapy, two of the 12 patients continued to have evidence of bone marrow disease. Samples from 29 PBSC harvests collected from nine patients were also analyzed for the presence of contaminating tumor cells by immunocytology. In each case, the stem cells were found to be free of tumor. Eleven of the 12 patients underwent myeloablative therapy and PBSC rescue; five patients remain alive without disease progression, 28+ to 53+ months from diagnosis, and six patients have developed recurrent disease. We conclude that PBSCs can be successfully harvested from children with NB, and used for hematopoietic reconstitution following myeloablative chemotherapy. However, more effective therapy for poor-risk NB patients is still urgently needed.

Adult↗
PubMed1997

Effect of metformin on glucose disposal and hyperinsulinaemia in a 14-year-old boy with acanthosis nigricans.

We report the treatment of a 14-year-old Indian boy with acanthosis nigricans and hyperinsulinaemia with metformin in an attempt to improve his skin lesions. Oral metformin was used for 6 months with assessment of insulin status during an intravenous glucose tolerance test and hyperinsulinaemic-euglycaemic clamping before and after treatment. The first-phase insulin response reduced from 19,593 to 5,410 pmol/l/min (normal 1,900-13,400), and the second-phase insulin response improved from 59,120 to 34,020 pmol/l/min (normal 2,900-18,100). During hyperinsulinaemic-euglycaemic clamping hepatic glucose production was normally suppressed prior to therapy, but peripheral glucose remained abnormally low, 152 and 138% of basal (expected 199%). The acanthosis nigricans remained unaltered but over this period puberty progressed and his body mass index increased. We conclude that, in this patient, metformin had a minimal effect on the hyperinsulinism and none on the acanthosis nigricans in the relatively short term, but further studies in more patients over longer time intervals are warranted.

Acanthosis Nigricans↗
PubMed1995

Cyclophosphamide/doxorubicin vs. cisplatin/teniposide in the treatment of children older than 12 months of age with disseminated neuroblastoma: a Pediatric Oncology Group Randomized Phase II study.

This prospective study was designed to estimate the response rates and to compare two drug pairs, cyclophosphamide/doxorubicin (Cy/A) and cisplatin/teniposide (P1/VM) in previously untreated patients with disseminated neuroblastoma > 12 months of age at diagnosis. Estimated complete clinical response rates after five courses of therapy were 13% (70 patients) and 22% (64 patients) for Cy/A and P1/VM, respectively (P = 0.17). After surgical removal of residual tumors in patients with partial response, the complete response rates were 27% and 34% (P = 0.50), respectively. The overall CR/PR rates after induction and surgery were 59% and 73% (P = 0.077). There was no significant difference in event free survival (P = 0.48) or survival (P = 0.40). Five year survival on the two arms were 14% (SE = 5%) and 12% (SE = 4%), respectively. Toxicity was significant but manageable. The Cy/A arm had significantly higher hematopoietic toxicity but significantly lower GI toxicity. Significant allergic reactions were seen with the P1/VM arm, none in the Cy/A arm. Given the activity of these two regimens, further therapy with a combination of these regimens is suggested.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Chest wall resection for Ewing's sarcoma of the rib: an unnecessary procedure. 1988. Updated in 1995.

Approximately 10% of all cases of Ewing's sarcoma arise from a rib. Conventional management has included chest wall resection (3 or more ribs) and radiation therapy. These forms of therapy have led to complications such as scoliosis and local deformity. The addition of radiation therapy can result in damage to the lung and adjacent viscera and also potentiate pulmonary restrictive disease. Between 1971 and 1978, 9 patients were treated with surgery, radiation therapy, and combination chemotherapy (three- or four-drug regimen). Only 2 patients (22%) survive. Since 1979, 14 patients were entered into a new protocol consisting of sequential induction chemotherapy, followed by delayed surgical resection whenever feasible. Three patients had complete resection of their primary lesion at onset. Initially, 7 patients had either biopsy (N = 4) or incomplete chest wall resection N = 3). All 4 patients with biopsy only at diagnosis had excellent responses to induction chemotherapy, allowing delayed resection of the involved rib without chest wall resection. Overall, 12 of 14 patients (86%) treated since 1979 survive, with only 2 receiving radiation therapy for residual disease in the primary rib site.

Bone Neoplasms↗
PubMed1994

Phase II investigational window using carboplatin, iproplatin, ifosfamide, and epirubicin in children with untreated disseminated neuroblastoma: a Pediatric Oncology Group study.

PURPOSE: Children less than 1 year of age with metastatic neuroblastoma NB are at high risk of death. The need to identify new and effective chemotherapy agents is clear. A study was conducted by the Pediatric Oncology Group (POG) to determine the efficacy and safety of administering two courses of a single phase II agent before conventional treatment as a means to evaluate new agents in this setting. PATIENTS AND METHODS: One hundred seventy-three eligible patients more than 1 year of age with disseminated neuroblastoma received two courses of one of the following: ifosfamide (IFOS) 2 g/m2/d for 4 days intravenously (IV) plus mesna; carboplatin (CARB) 560 mg/m2 i.v. over 1 hour; iproplatin (CHIP) 325 mg/m2 IV over 2 hours; or epirubicin (EPIR) 90 mg/m2 i.v. push. Following evaluation for response and toxicity, eligible patients were randomized to receive either cisplatin 90 mg/m2 i.v. on day 1, etoposide 200 mg/m2 i.v. on day 3, cyclophosphamide 150 mg/m2/d orally on days 7 to 13, doxorubicin 35 mg/m2 i.v. on day 14 (CECA), or cisplatin 40 mg/m2 IV on days 1 to 5 and etoposide 200 mg/m2 i.v. on days 2 to 4 alternating at 3-week intervals with cyclophosphamide 150 mg/m2/d orally on days 1 to 7 and doxorubicin 35 mg/m2 IV on day 8 (HDP/VP/CA). An additional 86 patients were randomized to receive either CECA or HDP/VP/CA without initial phase II therapy. RESULTS: After phase II therapy, only 20% of patients experienced grade 3/4 hematopoietic toxicity. No toxic deaths occurred. Objective response rates (partial responses [PRs] plus minor responses [MRs]) following IFOS, CARB, CHIP, and EPIR were 70%, 77%, 67%, and 26%, respectively. Following phase III treatment, there was no statistically significant difference in rates of complete response (CR)/PR or progressive disease (PD), or in time to PD of patients who participated in the phase II window versus those who received only CECA or HDP/VP/CA. CONCLUSION: IFOS, CARB, and CHIP are efficacious in neuroblastoma, are well tolerated, and should be incorporated into primary treatment regimens. Combination regimens using these agents may be possible, since most repeat courses were given within 2 weeks. Administering phase II therapy to untreated patients with high-risk tumors provides a unique and sensitive method to assess new agents without compromising patient outcome.

Adolescent↗
PubMed1992

Gut hormones and gastrointestinal motility in children with cystic fibrosis.

Intestinal dysmotility may be an important factor contributing to various gastrointestinal complications associated with cystic fibrosis. Motilin, enteroglucagon, neurotensin, and peptide YY may each play a role as endocrine hormones influencing gastrointestinal motor activity. Fasting children with cystic fibrosis (N = 8) and controls (N = 18) received a liquid nutrient test meal (fat 4 g/100 ml, protein 4 g/100 ml, carbohydrate 20 g/100 ml, 125 kcal/100 ml; 200 ml/m2) containing lactulose (5 g/100 ml), and the plasma concentrations of these peptides were studied. Mouth-to-cecum transit time was simultaneously studied using the breath H2 technique. Fasting levels of peptide YY and the postprandial response of all four peptides were significantly increased in those with cystic fibrosis. In repeat studies on those with cystic fibrosis after a period of altered pancreatic enzyme supplementation, no significant changes in peptide concentrations were observed. A rise in breath H2 permitting estimation of mouth-to-cecum transit time was noted in 17 control subjects (70-220 min, median 140). In contrast, a rise occurred in only two with cystic fibrosis after low-dose enzyme (70 and 180 min), and four after high-dose enzyme replacement (120-230 min, median 155). Altered gut hormone secretion may play a role in the pathophysiology of intestinal dysmotility in patients with cystic fibrosis.

Adolescent↗
PubMed1991

Primary extracranial neuroblastoma with central nervous system metastases characterization by clinicopathologic findings and neuroimaging.

The authors report the clinicopathologic and neuroimaging findings in ten children with primary abdominal or thoracic neuroblastoma who relapsed in the central nervous system (CNS) without evidence of concurrent intracranial extension from adjacent bone, dura, or dural sinus metastases. At diagnosis, the patients ranged in age from 0.3 to 4.5 years (median, 2 years). Their times to CNS relapse ranged from 2 to 34 months from diagnosis. In seven patients the relapse occurred from 1 to 14 months after elective discontinuation of therapy. In four patients, the CNS relapse was the primary (isolated) adverse event. Four patients could not be treated at the time of relapse, and they died within 7 days of progressive CNS disease. In the remaining group, craniospinal irradiation with or without administration of a platinum compound and an epipodophyllotoxin caused complete CNS remissions lasting 4, 5, 16, and 62+ months. Neuroimaging and autopsy findings indicated that cerebrospinal fluid is the major pathway for neuraxis dissemination by neuroblastoma cells. There was no evidence of dural penetration in any patient. The possibility of relapse in the neuraxis should be considered for any patient with neuroblastoma who had neurologic deterioration. A combination of craniospinal radiation and administration of a platinum compound and an epipodophyllotoxin will induce complete responses in some patients with neuraxis involvement by neuroblastoma, but the risk of subsequent failure outside the CNS remains high.

Abdominal Neoplasms↗
PubMed1991

Impact of intensified therapy on clinical outcome in infants and children with neuroblastoma: the St Jude Children's Research Hospital experience, 1962 to 1988.

To gauge the impact of intensified therapy on the survival of infants (younger than 1 year, n = 129) and children (greater than or equal to 1 year of age, n = 275) with neuroblastoma, we analyzed the results of eight successive clinical trials comparing various combinations of antineoplastic drugs, surgery, and radiotherapy. Changes in treatment did not affect the survival of children with involved noncontiguous lymph nodes or distant metastatic disease until the combination of cisplatin and teniposide (CDDP/VM26) was added to a basic regimen of cyclophosphamide and doxorubicin (CTX/DOX). The resulting 4-year survival was 28% +/- 5% (SE) compared with 7% +/- 2% for previous treatments (P less than .001 by the log-rank test). The 4-year survival of infants with metastatic disease was improved by administering CTX/DOX to all patients, reserving CDDP/VM26 for those whose disease was resistant to the former combination: 82% +/- 6% versus 45% +/- 8% in earlier studies; P less than .001. In the subset of infants whose tumors had disseminated to bone or bone marrow at diagnosis, this therapeutic approach increased the probability of long-term survival from 48% +/- 10% to 85% +/- 9% (P = .01). The small group of children over 1 year of age with localized unresectable tumors also fared significantly better with the switch to CTX/DOX chemotherapy (4-year survival, 93% +/- 7% v 42% +/- 13%; P = .02). Multivariate analysis indicated that young age, limited-disease stage, nonadrenal primary site, and intensified treatment were independent predictors of a more favorable outcome. We conclude that substantial advances in the treatment of neuroblastoma have occurred over the past 25 years at this institution. The current overall 4-year survival probability of 57% +/- 4% compares favorably with estimates for most other common solid tumors of childhood.

Age Factors↗
PubMed1990

Adjuvant chemotherapy for osteosarcoma of the extremity. Long-term results of two consecutive prospective protocol studies.

Seventy-six patients with classic high-grade osteosarcoma of an extremity received adjuvant chemotherapy by two protocols, initiated in 1972 and 1977, respectively, after appropriate amputations. Chemotherapy consisted of high-dose methotrexate, doxorubicin, and cyclophosphamide. Dose intensity of high-dose methotrexate and doxorubicin was greater for the patients treated with the protocol initiated in 1977. The proportion of long-term disease-free survivors on the two protocols are 46% and 56%. A better outcome (P = 0.042) was seen for the latter group, which received more intensive chemotherapy. Overall, metastases developed in 35 patients; in 19 who were receiving chemotherapy and in 16 after chemotherapy. The outcome for these two protocols, compared with two control groups that were given no chemotherapy or ineffective chemotherapy (biweekly vincristine and cyclophosphamide), confirms the results of controlled studies that showed an advantage of adjuvant chemotherapy after amputation for osteosarcoma.

Adolescent↗
PubMed1989

Clinical manifestations of ganglioneuroma.

Ganglioneuroma may occur spontaneously or after therapy for neuroblastoma. This lesion may be metastatic or unresectable in the primary site. The rarity of this situation and lack of understanding of the biology of this benign condition may lead to extensive, potentially life-threatening attempts at surgical resection or the futile use of chemotherapy or radiotherapy to try to cause regression or control growth. The authors present here several cases which demonstrate the multiple presentations of ganglioneuroma and the potential problems which may arise in their management.

Abdominal Neoplasms↗
PubMed1989

Chemotherapeutic management of epidural neuroblastoma.

Nine children with neuroblastoma and spinal cord compression were managed initially with chemotherapy induction without laminectomy or radiotherapy. Of the nine children seven are neurologically normal, one has minimal residual deficits, and one remains paraplegic. The excellent results in these children, plus nine patients previously reported, emphasizes the validity of this approach in children with epidural extension of neuroblastoma.

Child, Preschool↗
PubMed1989

Malignancy in the neonate.

From January 1962 to July 1988, 34 infants less than 29 days of age who had cancer were seen at St. Jude Children's Research Hospital (SJCRH). The malignancies in this group consisted of 19 neuroblastomas, 6 leukemias, 3 retinoblastomas, 2 Wilms' tumors, 2 melanomas, and 2 teratomas. Twenty-three patients (68%) are alive and free of disease 2 months to 24 years after diagnosis. We reviewed the presentation and initial symptoms, pathology reports, patient population, associated anomalies, potential genetic influences, and possible perinatal factors. The most common initial symptom was an enlarging abdomen or abdominal mass. Pathological findings were occasionally difficult to interpret; five additional infants who were referred to us did not have malignancies. There was no increased incidence of associated anomalies or perinatal insults. The only genetic factor was retinoblastoma in one parent of each infant diagnosed as having retinoblastoma. The possible etiology of neonatal tumors is discussed.

Humans↗
PubMed1989

Ifosfamide in pediatric malignant solid tumors.

Ifosfamide/mesna was given to 97 patients who had malignant solid tumors diagnosed before they were 21 years of age. Patients received 1.6 g/m2 ifosfamide daily x 5, given i.v. over 15 min, followed by 400 mg/m2 i.v. mesna at 15 min and 4 and 6 h after ifosfamide. Responses were noted in patients with osteosarcoma, Ewing's sarcoma, rhabdomyosarcoma and other soft-tissue sarcomas, rhabdoid tumor, neuroblastoma, Wilms' tumor, primitive neuroectodermal tumor, retinoblastoma, germ-cell tumors, and B-cell lymphoma. Toxicity included mild to moderate nausea and vomiting, transient, reversible myelosuppression, transient elevations of serum blood urea nitrogen (BUN) and creatinine and liver enzymes, infections, and self-limiting neurotoxicity characterized by changes in mental status, motor dysfunction, cranial nerve palsy, cerebellar dysfunction, and seizures. Neurotoxic symptoms were generally seen in patients who had previously received cisplatin. Ifosfamide is an important alkylating agent that should be combined with other agents in phase II and III trials. Alternate dose schedules should also be investigated.

Adolescent↗