Metastatic acinic cell carcinoma of the parotid gland with ectopic ACTH syndrome.
Explore the source record for details and available documents.
ACTH Syndrome, Ectopic↗
Biomedical subjects
Mary Davis
Publications and source records attributed to Mary Davis.
Abrupt tropical climate change: past and present.
Three lines of evidence for abrupt tropical climate change, both past and present, are presented. First, annually and decadally averaged delta(18)O and net mass-balance histories for the last 400 and 2,000 yr, respectively, demonstrate that the current warming at high elevations in the mid- to low latitudes is unprecedented for at least the last 2 millennia. Second, the continuing retreat of most mid- to low-latitude glaciers, many having persisted for thousands of years, signals a recent and abrupt change in the Earth's climate system. Finally, rooted, soft-bodied wetland plants, now exposed along the margins as the Quelccaya ice cap (Peru) retreats, have been radiocarbon dated and, when coupled with other widespread proxy evidence, provide strong evidence for an abrupt mid-Holocene climate event that marked the transition from early Holocene (pre-5,000-yr-B.P.) conditions to cooler, late Holocene (post-5,000-yr-B.P.) conditions. This abrupt event, approximately 5,200 yr ago, was widespread and spatially coherent through much of the tropics and was coincident with structural changes in several civilizations. These three lines of evidence argue that the present warming and associated glacier retreat are unprecedented in some areas for at least 5,200 yr. The ongoing global-scale, rapid retreat of mountain glaciers is not only contributing to global sea-level rise but also threatening freshwater supplies in many of the world's most populous regions.
Greenhouse Effect↗
Expression of LINE-1 p40 protein in pediatric malignant germ cell tumors and its association with clinicopathological parameters: a report from the Children's Oncology Group.
The long interspersed nucleotide element-1 (LINE-1) p40 protein was expressed in all 162 cases of childhood malignant germ cell tumor (MGCT) cells with weak, moderate, and strong immunoactivity in 43.8%, 37.7%, and 18.5%, respectively. Normal testicular tissue adjacent to tumors showed negative or weaker p40 expression than tumor cells. Multivariate analyses showed that strong expression of p40 was associated with poor differentiation, extragonadal site, and the histotype of yolk sac tumor. This study suggests that the active LINE-1 retrotransposon is a common event in pediatric MGCTs and abundant expression of p40 might play a role during the malignant transformation.
Adolescent↗
In utero exposure to female hormones and germ cell tumors in children.
BACKGROUND: Maternal exposure to exogenous female hormones during pregnancy has been implicated as a risk factor for malignant germ cell tumors (GCTs) in the offspring in some epidemiologic studies of testicular and ovarian carcinoma in adults. METHODS: From 1996 to 2002, 278 children younger than 15 years of age with malignant GCTs and 423 healthy controls, frequency-matched for geographic location, age, and sex were enrolled in a case-control study to investigate whether in utero exposure to female hormones is associated with the risk of malignant GCT in children. Cases were recruited from 84 institutions in the U.S. and controls were enrolled through random digit dialing. Information was obtained through telephone interview with the biological mothers of the subjects and through blinded review of the mothers' medical records. RESULTS: Neither self-reported (odds ratio [OR] = 1.15; 95% confidence interval [CI], 0.63, 2.12) nor medical chart based (OR = 1.14; 95% CI, 0.75, 1.73) maternal exposure to exogenous female hormones was related to malignant GCT risk. Pregnancy-related conditions that may have altered serum levels of circulating female hormones were also unrelated to the risk of GCT in the offspring. CONCLUSION: This study failed to provide strong evidence to support the hypothesis that maternal exposure to exogenous female hormones during pregnancy increases the risk of GCT in the offspring.
Adult↗
Functional communication and executive function in aphasia.
The purpose of this exploratory study was to investigate the relationship between functional communication and executive function ability in aphasia. Twenty-five participants with aphasia underwent examination with an extensive test battery including measures of functional communication, executive function ability, and language impairment. Compared to published norms, most participants did not perform within normal limits on the executive function tests. As expected, the correlation between severity of language impairment and functional communication ratings exceeded that among the executive functioning and functional communication measures. Eight of ten correlation coefficients for the relationship between executive functioning and functional communication reached statistical significance suggesting a clear relationship between scores on the executive functioning measures and functional communication ability. Based on these results, it appears that decreased executive functioning ability may coincide with decreased functional communication ability in persons with aphasia.
Adult↗
Alpha-thalassemia major presenting in a term neonate without hydrops.
We describe the clinical and pathologic features of an unusual case of alpha-thalassemia major in a patient who survived to term and lived for 9 days. The neonate was nonhydropic and the clinical picture was dominated by severe hypoxia with pulmonary hypertension. The diagnosis was not suspected until postnatal examination of the blood smear, which prompted the performance of hemoglobin electrophoresis and subsequent molecular confirmation. This case illustrates that alpha-thalassemia major should be in the differential diagnosis of hypoxic neonates even in the absence of hydrops.
Diagnosis, Differential↗
Parental occupational exposure to pesticides and childhood germ-cell tumors.
In a recently completed US case-control study (Children's Oncology Group, 1993-2001) with 253 cases and 394 controls, the authors investigated the association between parental occupational exposure to pesticides and risk of childhood germ-cell tumors. Information on occupational pesticide exposure was collected using job-specific module questionnaires and assessed by an experienced industrial hygienist. Odds ratios for childhood germ-cell tumors associated with maternal exposures before pregnancy, during pregnancy, and after the birth of the index child were 1.0 (95% confidence interval (CI): 0.8, 1.4), 1.1 (95% CI: 0.7, 1.6), and 1.3 (95% CI: 0.9, 1.8), respectively. Paternal exposures before pregnancy, during pregnancy, and after the birth of the index child were not related to germ-cell tumors (odds ratios (ORs) were 0.9 (95% CI: 0.7, 1.2), 0.8 (95% CI: 0.5, 1.2), and 0.8 (95% CI: 0.5, 1.3), respectively). When both parents had ever been occupationally exposed to pesticides before the index pregnancy, the odds ratio was 0.8 (95% CI: 0.4, 1.3). Subgroup analyses showed a positive association between maternal exposure to herbicides during the postnatal period and risk of germ-cell tumors in girls (OR = 2.3, 95% CI: 1.0, 5.2) and an inverse association between paternal exposure to pesticides during the index pregnancy and germ-cell tumors in boys (OR = 0.2, 95% CI: 0.1, 1.0). This study did not provide strong evidence supporting a relation between parental pesticide exposure in the workplace and risk of germ-cell tumors among offspring.
Adolescent↗
Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer.
PURPOSE: To evaluate the effect of BLP25 liposome vaccine (L-BLP25) on survival and toxicity in patients with stage IIIB and IV non-small-cell lung cancer (NSCLC). Secondary objectives included health-related quality of life (QOL) and immune responses elicited by L-BLP25. PATIENTS AND METHODS: Patients with an Eastern Cooperative Oncology Group performance status of 0 to 2 and stable or responding stage IIIB or IV NSCLC after any first-line chemotherapy were prestratified by stage and randomly assigned to either L-BLP25 plus best supportive care (BSC) or BSC alone. Patients in the L-BLP25 arm received a single intravenous dose of cyclophosphamide 300 mg/m2 followed by eight weekly subcutaneous immunizations with L-BLP25 (1,000 microg). Subsequent immunizations were administered at 6-week intervals. RESULTS: The survival results indicate a median survival time of 4.4 months longer for patients randomly assigned to the L-BLP25 arm (88 patients) compared with patients assigned to the BSC arm (83 patients; adjusted hazard ratio [HR] = 0.739; 95% CI, 0.509 to 1.073; P = .112). The greatest effect was observed in stage IIIB locoregional (LR) patients, for whom the median survival time for the L-BLP25 arm has not yet been reached compared with 13.3 months for the BSC arm (adjusted HR = 0.524; 95% CI, 0.261 to 1.052; P = .069). No significant toxicity was observed. QOL was maintained longer in patients on the L-BLP25 arm. CONCLUSION: L-BLP25 maintenance therapy in patients with advanced NSCLC is feasible with minimal toxicity. The survival difference of 4.4 months observed with the vaccine did not reach statistical significance. In the subgroup of patients with stage IIIB LR disease, a strong trend in 2-year survival in favor of L-BLP25 was observed.
Aged↗
Environmental exposure to residential pesticides, chemicals, dusts, fumes, and metals, and risk of childhood germ cell tumors.
We examined relationships between exposure to residential pesticides, chemicals, dusts, fumes, and metals, and childhood germ cell tumors (GCTs) in the largest case-control study to date on the topic. We recruited 272 children under 15 years old who had GCT diagnosed between January 1, 1993 and December 31, 2001. Controls were selected by random-digit dialing and were frequency matched to cases by sex, age, and geographic area. Telephone interviews and self-administered questionnaires of parents were used to collect exposure information. We used unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). Maternal and paternal exposure from 6 months before pregnancy to during breastfeeding and children's postnatal exposure to residential pesticides were generally unrelated to risk of childhood GCT. Elevated OR were observed for mothers' exposure to hair dyes 1 month before pregnancy for boys (OR = 1.7, 95% CI = 1.0-2.8) and during breastfeeding for boys and girls combined, and for girls (OR = 1.5, 95% CI = 1.0-2.2 and OR = 1.7, 95% CI = 1.1-2.6, respectively). Among boys, OR for paternal exposure to insecticides more often than four times or exposure to indoor insecticides more often than three times were 0.5 (95% CI = 0.2-0.9, trend test p = 0.05) and 0.3 (95% CI = 0.2-0.8, trend test p = 0.02) during the index pregnancy. Overall this study produced no strong evidence linking parental and child residential exposure to pesticides, certain chemicals, dusts, fumes, and metals to increased risk of childhood GCT. Statistically significant associations need to be confirmed in future studies.
Adolescent↗
Risk of childhood germ cell tumors in association with parental smoking and drinking.
BACKGROUND: The etiology of childhood germ cell tumors (GCT) is not well understood. The Children's Oncology Group conducted the largest case-control study of childhood GCT to investigate whether parental exposures to smoking and alcohol contributed to the disease. METHODS: Cases included 274 children with GCT diagnosed between January 1, 1993 and December 31, 2001 who were age <15 years. Controls (n=421) were selected by random digit dialing and were frequency matched based on gender, age (+/-1 year), and geographic area. Exposure information was collected from subjects' parents using independent telephone interviews and self-administrated questionnaires. RESULTS: No association was found between parental smoking or drinking alcohol and risk of childhood GCT (for smoking: odds ratio [OR]=1.0, 95% confidence interval [95% CI], 0.8-1.3 and OR = 1.2, 95% CI, 0.9-1.5, for mothers and fathers, respectively; for drinking: OR=0.9, 95% CI, 0.7-1.2 and OR=1.0, 95% CI, 0.8-1.3, for mothers and fathers, respectively). No significant trend was observed for length of maternal exposure to passive smoking during the index pregnancy and GCT risk (for total subject: P=0.77; boys: P=0.52; girls: P=0.93). CONCLUSIONS: The authors found no evidence that childhood GCT was related to prenatal exposure to parental cigarette smoking, alcohol drinking, and maternal passive smoking.
Adolescent↗
Parkin disease in a Brazilian kindred: Manifesting heterozygotes and clinical follow-up over 10 years.
We report on a large Brazilian kindred with young-onset parkinsonism due to either a homozygous or heterozygous mutation in parkin. A total of 6 members were affected: 5 were homozygous and 1 heterozygous for a deletion in exon 4. Two other heterozygotes also had extrapyramidal signs. All affected subjects showed characteristic features of parkin disease with foot dystonia and an excellent response to levodopa complicated by motor fluctuations and dyskinesia within 3 years of therapy. Careful clinical follow-up over 10 years showed the phenotype was similar in all the homozygotes with asymmetrical limb bradykinesia and early walking difficulties. Some acceleration of disability was observed in some of the cases as they entered the third decade of illness, but dementia was absent.
Adult↗
Phase II study of perifosine in previously untreated patients with metastatic melanoma.
PURPOSE: To assess the response rate and toxicity of the alkylphosphocholine analogue, perifosine, in patients with metastatic or recurrent malignant melanoma. PATIENTS AND METHODS: Patients had histologically proven, unidimensionally measurable disease which was incurable by standard therapy. Prior adjuvant immunotherapy was allowed but patients had not received prior chemotherapy. Perisfosine was given orally as a loading dose of 900 mg on day 1 followed by a maintenance dose of 150 mg po on days 2-21 in a 28 day cycle. The loading dose was 300 mg on day 1 of all subsequent cycles. Tumour response was assessed every 2 cycles. RESULTS: 18 patients were accrued over 7 mos. No objective responses occurred in the 14 evaluable patients. Three patients (21%) achieved stable disease after 2 cycles and 11 had progression. Seventeen patients were evaluable for toxicity. Grade 3 or 4 non-hematologic toxicities included: diarrhea (12%), arthralgia (12%), nausea (6%), headache (6%), and fatigue (6%). No grade 3 or 4 hematological or biochemical toxicity were observed. Seventy-seven percent of patients received >or=90% of planned cycle 1 dose intensity and 58% received >or=90% of planned dose for cycle 2+. Four patients required dose reductions; treatment was delayed in 5 patients; and 5 patients missed doses because of toxicity. CONCLUSIONS: Perifosine can be safely administered when given as an initial loading dose followed by daily maintenance therapy over 28 days. Gastrointestinal toxicity is common but generally of low grade. Hematological toxicity is minimal. No objective responses were observed. No further development of single-agent perifosine is recommended in malignant melanoma.
Adult↗
(-)-Gossypol enhances response to radiation therapy and results in tumor regression of human prostate cancer.
Radioresistance markedly impairs the efficacy of tumor radiotherapy and involves antiapoptotic signal transduction pathways that prevent radiation-induced cell death. The majority of human prostate cancers overexpress the important antiapoptotic proteins Bcl-2 and/or Bcl-xL, which render tumors resistant to radiation therapy. (-)-Gossypol, a natural polyphenol product from cottonseed, has recently been identified as a potent small molecule inhibitor of both Bcl-2 and Bcl-xL. In the current study, we investigated the antitumor activity of (-)-gossypol in prostate cancer and tested our hypothesis that (-)-gossypol may improve prostate cancer's response to radiation by potentiating radiation-induced apoptosis and thus making cancer cells more sensitive to ionizing radiation. Our data show that (-)-gossypol potently enhanced radiation-induced apoptosis and growth inhibition of human prostate cancer PC-3 cells, which have a high level of Bcl-2/Bcl-xL proteins. Our in vivo studies using PC-3 xenograft models in nude mice show that orally given (-)-gossypol significantly enhanced the antitumor activity of X-ray irradiation, leading to tumor regression in the combination therapy. In situ terminal deoxynucleotidyl transferase-mediated nick end labeling staining showed that significantly more apoptotic cells were induced in the tumors treated with (-)-gossypol plus radiation than either treatment alone. Anti-CD31 immunohistochemical staining indicates that (-)-gossypol plus radiation significantly inhibited tumor angiogenesis. Our results show that the natural polyphenol inhibitor of Bcl-2/Bcl-xL, (-)-gossypol, can radiosensitize prostate cancer in vitro and in vivo without augmenting toxicity. (-)-Gossypol may improve the outcome of current prostate cancer radiotherapy and represents a promising novel anticancer regime for molecular targeted therapy of hormone-refractory prostate cancer with Bcl-2/Bcl-xL overexpression.
Animals↗
Randomized phase II feasibility study of combining the matrix metalloproteinase inhibitor BMS-275291 with paclitaxel plus carboplatin in advanced non-small cell lung cancer.
BACKGROUND: This randomized, double-blind, placebo-controlled study was designed to assess whether the addition of the matrix metalloproteinase (MMP) inhibitor BMS-275291 to combined paclitaxel and carboplatin chemotherapy had an adverse impact on expected tumor response or had significant toxicity, especially arthrotoxicity, in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Seventy-five chemotherapy-naive patients with stage IIIB-IV NSCLC were randomly assigned to BMS-275291 or placebo. All patients received paclitaxel 200mg/m(2) as a continuous 3-hour infusion followed by carboplatin calculated using the Calvert formula for a target AUC of 6 mg / (ml min), every 21 days for a maximum of eight cycles. BMS-275291 or placebo was administered on an outpatient basis at a daily oral dosage of 1200 mg. RESULTS: All 75 patients were evaluable for toxicity and 65 (86.7%) for response. Drug-related arthrotoxicity > or =grade 2 occurred in 12 patients (31.6%) in the BMS-275291 group (lower limit of one-sided 95% CI: 19.3) and in 11 patients (29.7%) in the placebo treatment arm. The incidence of rash was higher in patients receiving BMS-275291 (28.9% versus 18.9%). An objective response rate of 21.9% was observed in the BMS-275291 treatment arm and 36.4% in the placebo arm. CONCLUSION: BMS-275291 plus paclitaxel/carboplatin was well tolerated and active in advanced non-small cell lung cancer. Treatment with BMS-275291 was not limited by drug-related arthrotoxicity and tumor response was as expected. As planned, patient accrual continued to further investigate the effect of BMS-275291 on overall and progression-free survival in a phase III setting.
Administration, Oral↗
The effect of neoadjuvant chemotherapy and surgery in children with malignant germ cell tumors of the genital region: a pediatric intergroup trial.
PURPOSE: This study was designed to evaluate (1) the efficacy of standard or high-dose cisplatin with etoposide and bleomycin and (2) the role of surgical resection in infants and children with malignant germ cell tumors (MGCT) of the genital region. METHODS: Fourteen of 317 children enrolled in to the Pediatric Oncology Group/Children's Cancer Group intergroup study of MGCT from 1990 through 1996 had genital tumors. Thirteen were eligible for inclusion (12 vaginal, one penile). The initial procedure was biopsy in 11 and subtotal resection in 2. Patients were assigned randomly to receive 4 cycles of etoposide, bleomycin, and either standard or high-dose cisplatin. RESULTS: Nine children underwent postchemotherapy excision of the residual site, and 2 had subsequent biopsies to confirm a complete response. Two with relapse were saved with additional therapy, and one with progressive disease died. The 4-year event-free survival rate in these patients is 76.2% +/- 13.1%, and 4-year survival rate is 91.7% +/- 8.4%. CONCLUSIONS: The author conclude that: (1) the current survival rate for genital MGCT is excellent, (2) delayed surgical resection with organ preservation is not associated with an adverse outcome, and (3) the treatment comparison of the effect of cisplatin dose was inconclusive in this small study population.
Antineoplastic Combined Chemotherapy Protocols↗
Excellent outcome in patients with stage I germ cell tumors of the testes: a study of the Children's Cancer Group/Pediatric Oncology Group.
BACKGROUND/PURPOSE: The aim of this study was to correlate outcomes in patients with stage I testicular germ cell tumors with compliance to surgical guidelines and to confirm previous single-institution experiences that show excellent disease-free survival rates when treated with orchiectomy alone. METHODS: Sixty-three patients were entered into this intergroup study (Children's Cancer Group 8881/Pediatric Oncology Group 9048) between 1990 and 1996. Surgical guidelines for orchiectomy included an inguinal approach, early vascular control of the cord structures, and a hemiscrotectomy if a transscrotal violation occurred. Failure of tumor marker normalization or subsequent elevation suggested advanced disease requiring further surgery and chemotherapy. Survival curves were compared using the log-rank test. RESULTS: The median age was 16 months (range, 1 month to 5.6 years). Progression of disease occurred in 11 patients. The 6-year event-free survival (EFS) was 78.5% + 7%. The overall 6-year survival rate was 100%. Adherence to all guidelines was confirmed in only 43 patients (69%). Overall, there was no statistical significance in event-free survival rates between patients who had a correct surgical approach and all patients who had surgical violations; however, 4 patients with transscrotal violations showed a significantly higher rate of disease recurrence. CONCLUSIONS: Patients with stage I germ cell tumors of the testes have excellent survival rates when treated with surgery alone. Despite numerous surgical guideline violations, event-free survival in this multiinstitutional study was similar to previous single-institution reports. All patients with relapse or progression of their disease appear to be cured with further surgical excision and chemotherapy.
Chemotherapy, Adjuvant↗
Inflammatory pseudotumor of the spleen in a 6-year-old child: a clinicopathologic study.
Inflammatory pseudotumors of the spleen are extremely rare in children. To our knowledge, only 3 cases of splenic inflammatory pseudotumors have been reported. An inflammatory pseudotumor of the spleen was found incidentally during the workup of vesicoureteral reflux disease in a 6-year-old girl. The clinical, pathologic, immunophenotypic, and molecular features and the differential diagnostic features are discussed here. Splenic inflammatory pseudotumors, although rare, should be considered in the differential diagnosis of a mass lesion of the spleen in children.
Child↗
Concurrent chemoradiotherapy with gemcitabine and cisplatin for pancreatic cancer: from the laboratory to the clinic.
PURPOSE: We have reported that gemcitabine and concurrent radiation is a promising therapy for patients with pancreatic cancer. We investigated whether the addition of cisplatin, which may increase the systemic efficacy of gemcitabine, would be synergistic with gemcitabine and/or radiation in human pancreatic cancer cell lines. METHODS AND MATERIALS: BxPc3 and Panc-1 human pancreatic cancer cells were treated with three different schedules before radiation: (A) a sequential incubation of gemcitabine for 2 h followed by cisplatin for 2 h, (B) gemcitabine for 2 h, followed by washout of drug, replenishment of media for a 24-h incubation, followed by cisplatin for 2 h, and (C) gemcitabine for 24 h with a concurrent incubation of cisplatin for the last 2 h. Cells were assessed for clonogenic survival using a standard assay. Synergism was evaluated by the median effect analysis. RESULTS: The schedule shown to be maximally synergistic for both cell lines was the consecutive 2-h gemcitabine, 2-h cisplatin exposure, particularly at surviving fractions of <0.5. Cisplatin did not produce radiosensitization nor did it affect gemcitabine-mediated radiosensitization. CONCLUSION: Cisplatin produces synergistic cytotoxicity with gemcitabine without compromising gemcitabine-mediated radiosensitization. On the basis of these laboratory and previous clinical observations, we have initiated a Phase I trial of cisplatin plus gemcitabine and radiotherapy in patients with unresectable pancreatic cancer.
Cisplatin↗