The importance of peer reviewing.
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Humans↗
Biomedical subjects
J Franklin
Publications and source records attributed to J Franklin.
Non-Hodgkin's lymphoma after primary Hodgkin's disease in the German Hodgkin's Lymphoma Study Group: incidence, treatment, and prognosis.
PURPOSE: The cumulative incidence for non-Hodgkin lymphoma's (NHL) after primary Hodgkin's disease (HD) ranges between 1% and 6%. To investigate the course of disease for secondary NHL, we retrospectively analyzed patients treated within clinical trials of the German Hodgkin's Lymphoma Study Group (GHSG) since 1981. PATIENTS AND METHODS: From 1981 to 1998, the GHSG conducted three generations of clinical trials for the treatment of primary HD involving a total of 5,406 patients. Reference histology by an expert panel was obtained for 4,104 of the patients. Data on incidence, treatment, and outcome of secondary NHL were updated in March 1999. RESULTS: At first diagnosis of HD, the pathologists rejected 114 (2.1%) of 5,520 cases initially diagnosed as HD and rediagnosed them as primary NHL. Fifty-two (0.9%) of the remaining 5,406 patients developed a secondary NHL. One patient was excluded from further analyses because of insufficient documentation. Six patients had no further therapy because of patient refusal (n = 1) or rapidly progressive disease (n = 5). For the remaining 45 patients, overall response rate was 43% (36% complete response and 7% partial response). The actuarial 2-year freedom from treatment failure (FFTF) and overall survival (OS) for all patients was 24% and 30%, respectively, and for patients with diffuse large-cell lymphoma, it was 28% and 35%, respectively. Time of occurrence of secondary NHL after first diagnosis of HD and variables employed in the age-adjusted International Prognostic Factor Index (IPFI) significantly influenced treatment outcome. CONCLUSION: In the GHSG, the incidence of secondary NHL with 0.9% is relatively low compared with previously reported series. The prognosis of secondary NHL seems dismal and is significantly influenced by time of occurrence and the age-adjusted IPFI. In a subset of patients with secondary NHL, long-term disease-free survival could be achieved.
Actuarial Analysis↗
Plasma pharmacokinetics and cerebrospinal fluid penetration of thioguanine in children with acute lymphoblastic leukemia: a collaborative Pediatric Oncology Branch, NCI, and Children's Cancer Group study.
PURPOSE: In preclinical studies, thioguanine (TG) has been shown to be more potent than the standard acute lymphoblastic leukemia (ALL) maintenance agent, mercaptopurine (MP), suggesting that TG may be more efficacious than MP in the treatment of childhood ALL. As part of a pilot trial in which TG was used in place of MP, we studied the plasma pharmacokinetics of oral TG and measured steady-state plasma and CSF TG concentrations during a continuous intravenous infusion (CIVI) in children with newly diagnosed standard-risk ALL. METHODS: Nine plasma samples were collected after each patient's first 60 mg/m2 oral TG dose during maintenance. CIVI TG (20 mg/m2/h over 24 h) was administered during the consolidation phase of therapy, and simultaneous plasma and CSF samples were collected near the end of the infusion. TG was measured by reverse-phase HPLC with ultraviolet detection. Erythrocyte TG nucleotide (TGN) concentrations were measured 7 days after a course of CIVI TG and prior to the start of each maintenance cycle. RESULTS: After oral TG (n = 35), the mean (+/- SD) peak plasma concentration was 0.46 +/- 0.68 microM and the AUC ranged from 0.18 to 9.5 microM.h (mean 1.5 microM.h). Mean steady-state plasma and CSF TG concentrations during CIVI (n = 33) were 2.7 and 0.5 microM, respectively. The mean (+/- SD) TG clearance was 935 +/- 463 ml/min per m2. Plasma TG concentrations did not correlate with erythrocyte TGN concentrations after oral or CIVI TG. The 8-OH-TG metabolite was detected in plasma and CSF. CONCLUSIONS: TG concentrations that are cytotoxic to human leukemia cell lines can be achieved in plasma after a 60 mg/m2 oral dose of TG and in plasma and CSF during CIVI of TG.
Administration, Oral↗
The effect of salinity on the emergence and seedling growth of Picea mariana, Picea glauca, and Pinus banksiana.
Mining operations in areas of the boreal forest have caused salinity issues to be a major concern for reclamation. One of the factors determining successful reclamation is the ability of species to self-propagate. The effects of salinity on the seedling emergence and early growth of three boreal forest conifers: Picea mariana, Picea glauca, and Pinus banksiana were determined. Seeds were planted in sand moistened with solutions of various concentrations of sodium chloride or sodium sulfate. Seedling emergence was monitored on a daily basis and growth parameters assessed after 6 weeks. The emergence of Pinus banksiana seedlings was least affected by salinity, and at certain concentrations, emergence even appeared to be stimulated by the presence of salt. Picea glauca was the most sensitive of the species studied. Hypertrophia was observed in all species at high concentrations of Na2SO4, and an increase in salt levels caused a corresponding reduction in seedling height and weight, root length and number of lateral roots.
Environmental Monitoring↗
Dose escalation of cytotoxic drugs using haematopoietic growth factors: a randomized trial to determine the magnitude of increase provided by GM-CSF.
BACKGROUND: The magnitude of chemotherapy dose escalation made possible by the use of recombinant haematopoietic growth factors has not been quantified in a randomized trial. PATIENTS AND METHODS: Patients with refractory or relapsing Hodgkin's disease were randomized to receive the Dexa-BEAM regimen with escalating etoposide doses supported by placebo or granulocyte-macrophage colony-stimulating factor (GM-CSF). Using an adaptive sampling method independently in both arms, the etoposide dose was escalated until the maximal tolerated dose for the first cycle was reached. RESULTS: Thirty patients were randomized to GM-CSF and thirty to placebo. The etoposide dose could be escalated considerably in both treatment arms. Maximal etoposide dose for the first cycle was 1920 mg/m2 for patients receiving GM-CSF and 1160 mg/m2 for patients receiving placebo (P = 0.045 one-sided), corresponding to a 65% higher etoposide dose and a 13% higher dose intensity with GM-CSF. Dose-limiting events were similar in both arms, consisting mainly of prolonged neutropenia and consecutive infections. Treatment efficacy was not different in the two treatment groups. CONCLUSIONS: While GM-CSF permits a somewhat higher dose escalation than placebo, the increase in dose intensity provided by GM-CSF is small. The use of CSF for interval reduction rather than dose escalation is the more effective strategy for dose intensification.
Adolescent↗
Delayed emergency department presentation in critically ill patients.
OBJECTIVES: To determine the frequency and causes of delayed emergency department presentation in critically ill patients who did not have acute myocardial infarction and to evaluate whether factors such as age, gender, prior medical advice, lack of insurance, or low educational level are associated with delayed presentation. DESIGN: Prospective, descriptive analysis. SETTING: Emergency department and medical intensive care unit of an urban county hospital. PATIENTS: All adult patients admitted from the emergency department to the medical intensive care unit for reasons other than unstable angina, acute myocardial infarction, or stroke over two 9-wk blocks. INTERVENTIONS: Within 72 hrs of intensive care unit admission, patients or their families were interviewed to determine time elapsed between the onset of symptoms and patient emergency department presentation and to elicit reasons for delays in seeking medical treatment. MEASUREMENTS AND MAIN RESULTS: We interviewed 155 of 173 (90%) of eligible patients and found that 58% waited >24 hrs before presenting to the emergency department. The most commonly cited primary reason for delays were beliefs that symptoms were not serious enough for emergency care (31%) and that symptoms would resolve spontaneously (29%). Most (55%) sought medical treatment only at the urging of family members or other advocates. Although variables such as lack of insurance and low educational level were not associated with delayed presentation, male gender and having sought medical advice before presenting to the emergency department were significantly associated with delay (p =.036 for each). CONCLUSIONS: Because of poor understanding of the gravity and natural progression of their symptoms, most critically ill patients waited >24 hrs to present to our emergency department. Education on warning symptom recognition for serious illnesses may be warranted not only for patients themselves but also for family members and caregivers.
Adult↗
A new approach to monitoring exercise training.
The ability to monitor training is critical to the process of quantitating training periodization plans. To date, no method has proven successful in monitoring training during multiple types of exercise. High-intensity exercise training is particularly difficult to quantitate. In this study we evaluate the ability of the session rating of perceived exertion (RPE) method to quantitate training during non-steady state and prolonged exercise compared with an objective standard based on heart rate (HR). In a 2-part design, subjects performed steady state and interval cycle exercise or practiced basketball. Exercise bouts were quantitated using both the session RPE method and an objective HR method. During cycle exercise, the relationship between the exercise score derived using the session RPE method and the HR method was highly consistent, although the absolute score was significantly greater with the session RPE method. During basketball, there was a consistent relationship between the 2 methods of monitoring exercise, although the absolute score was also significantly greater with the session RPE method. Despite using different subjects in the 2 parts of the study, the regression relationships between the session RPE method and the HR method were nearly overlapping, suggesting the broad applicability of this method. We conclude that the session RPE method is a valid method of quantitating exercise training during a wide variety of types of exercise. As such, this technique may hold promise as a mode and intensity-independent method of quantitating exercise training and may provide a tool to allow the quantitative evaluation of training periodization plans.
Adult↗
European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease: histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes.
Paraffin blocks and clinical data from 521 patients with lymphocyte predominance Hodgkin disease (LPHD) diagnosed between 1970 and 1994 were collected from 16 European and United States oncological centers to establish the pathologic and clinical characteristics of a large patient cohort, to determine how frequent T-cell-rich large B-cell lymphoma (TCRLBCL) is among LPHD, and to find differential diagnostic criteria distinguishing between the 2 lymphoma categories. For this purpose, conventionally and immunohistologically stained sections were reviewed by a panel of hematopathologists. The diagnosis of LPHD was confirmed in only 219 of the 388 assessable cases (56.5%). This low confirmation rate was due mainly to the presence of a new variant of classical Hodgkin disease (CHD), which resembled, in terms of nodular growth and lymphocyte-richness, nodular LPHD and, in terms of the immunophenotype of the tumor cells, CHD and was designated nodular lymphocyte-rich CHD (NLRCHD). The nodules of LRCHD consisted-as in nodular LPHD-predominantly of B cells but differed from those present in LPHD in that they represented expanded mantle zones with atrophic germinal centers. Clinically, patients with LPHD and NLRCHD showed similar disease characteristics at presentation but differed in the frequency of multiple relapses and prognosis after relapse. Patients with LPHD and NLRCHD clearly differed from patients with CHD with nodular sclerosis or mixed cellularity, as they presented with an earlier disease stage and infrequent mediastinal involvement. As 97% of the LPHD cases showed a complete or partial nodular growth pattern, their differentiation from TCRLBCL was a rare problem in the present series. (Blood. 2000;96:1889-1899)
Adolescent↗
Prognostic factors and treatment outcome in primary progressive Hodgkin lymphoma: a report from the German Hodgkin Lymphoma Study Group.
To determine prognostic factors and treatment outcome, patients with primary progressive Hodgkin lymphoma (HD) registered in the database of the German Hodgkin Lymphoma Study Group (GHSG) were analyzed retrospectively. Detailed records from randomized prospective multicenter trials performed between 1988 and 1998 of 3807 patients recruited in these trials were reviewed. The median age of the 206 patients available was 34 years (range, 16-71). Fifty-seven patients (28%) in intermediate stage and 149 patients (72%) in advanced stage developed progressive disease (PD). One hundred and fifty-three patients (74%) were treated with salvage chemotherapy, 47 patients (23%) with salvage radiotherapy, and 6 patients (3%) did not receive any therapy due to rapid PD. Seventy patients (34%) were treated with high-dose chemotherapy (HDCT) and autologous stem cell transplantation. The 5-year freedom from second failure (FF2F) and overall survival (OS) for all patients were 17% and 26%, respectively. The 5-year FF2F and OS for patients treated with HDCT were 31% and 43%, respectively. In multivariate analysis low Karnofsky performance score at the time of progression (P <.0001), age above 50 years (P =.019), and failure to attain a temporary remission on first-line treatment (P =.0003) were significant adverse prognostic factors for OS. Patients with none of these risk factors had a 5-year OS of 55% compared with 0% for patients with all 3 of these unfavorable prognostic factors. Although HDCT is a reasonable option for selected patients with primary progressive HD, the majority did not receive HDCT. Interestingly, salvage radiotherapy gave promising results in patients with localized PD. (Blood. 2000;96:1280-1286)
Adolescent↗
Tissue eosinophilia correlates strongly with poor prognosis in nodular sclerosing Hodgkin's disease, allowing for known prognostic factors.
Although eosinophilic granulocytes are frequently observed in lymphatic tissue of Hodgkin's patients, no substantial data reveal the prognostic role, if any, of tissue eosinophilia. Thus, eosinophilia was analyzed histologically in 1511 diagnostic biopsy specimens of patients treated under protocol therapy of the German Hodgkin's Lymphoma Study Group between 1988 and 1994. Prominent eosinophilia was seen in 38% of cases, which differed among the histologic types of Hodgkin's disease (HD): none in lymphocyte predominant, 14% in lymphocyte rich classical, 40% in nodular sclerosis grade 1 (NS-1), 55% in nodular sclerosis grade 2, 43% in mixed cellularity (MC), and 54% in lymphocyte depleted. In a multivariate analysis, tissue eosinophilia proved to be the strongest prognostic factor for freedom from treatment failure (P <. 001) and overall survival (P <.001) in a stage-stratified model. Among NS-1 patients, the effect was highly significant. In MC, no significant effect of eosinophilia on survival could be demonstrated. Eosinophils secrete CD30 ligand that is capable of binding to CD30 positive HD cells. The activation of TRAF2, followed by NF-kappaB, which occurs on CD30L/CD30 binding, may explain the neoplastic proliferation and apoptosis protection of HD cells. TRAF2 is also activated by EBV-LMP expression, which is detectable in the majority of MC but not NS cases. In addition to the possibility that eosinophils are only passive indicators for other unknown prognostic determinants, it may be concluded that the positive clinical outcome of eosinophilia-negative NS cases could be due to lower NF-kappaB activity. (Blood. 2000;95:1207-1213)
Adolescent↗
How to restrict liver biopsy to high-risk patients in early-stage Hodgkin's disease. German Hodgkin's Lymphoma Study Group.
Liver biopsy is an invasive diagnostic method for detecting liver involvement (LI) in Hodgkin's disease (HD). The aim of this retrospective study was to determine and evaluate a method for restricting liver biopsy to a subset of patients. Between 1988 and 1994, a total of 2,016 patients with HD were treated within the HD4-6 study protocol of the German Hodgkin's Lymphoma Study Group (GHSG). We investigated the predictive power of abdominal ultrasound (US) and computed tomography (CT), as well as of various clinical factors related to LI, using univariate and multivariate methods. LI occurred in 4.9% of all patients (99/2,016) and in 3.0% of those who, if LI were disregarded, would have been included in clinical stages I and II. In multivariate analysis the presence of LI was significantly associated with splenic involvement or infradiaphragmatic involvement, absence of mediastinal involvement, serum alkaline phosphatase (SAP) level over 230 units/l, and age over 40 years. We used these factors to define a risk score for LI. LI is very rare in patients who would otherwise be in clinical stages I or II, but knowledge of LI is important because it has therapeutic consequences. With our risk score, liver biopsy is indicated for approximately one quarter of these patients otherwise in clinical stages I or II.
Adolescent↗
Is the international prognostic score for advanced stage Hodgkin's disease applicable to early stage patients? German Hodgkin Lymphoma Study Group.
BACKGROUND: The seven-factor International Prognostic Score (IPS) has been developed and verified for patients with advanced stage Hodgkin's disease (HD). This report aims to assess the predictive power of the IPS for early stage HD patients. PATIENTS AND METHODS: Data on patient characteristics, therapy and follow-up were available for 1424 adult patients in clinical stages I-IIIA treated for primary HD in two German Hodgkin's Lymphoma Study Group (GHSG) trials (1988-1994). Patients with risk factors or in stage IIIA received chemo radiotherapy (CMT; trial HD5); others received extended field radiotherapy (RT) alone (HD4). The IPS could be calculated for 712 HD5 and 249 HD4 patients (70%). The prognostic value of the IPS and its component factors was assessed using Cox proportional hazards regression. A search was made for additional factors which could add predictive power to the IPS. RESULTS: The IPS identified 40% of the unfavourable early stage patients with an 8% lower disease-free survival at six years (hazard ratio 1.66, P = 0.0018). The factor 'low albumin' was the only score component giving a significant individual contribution. Allowing for the IPS, extranodal involvement, particularly in stages IIB-IIIA, was associated with worse prognosis, but no further significantly prognostic factors were revealed. The IPS identified a similar hazard ratio in HD4, although here the effect was not significant. CONCLUSIONS: The IPS for advanced HD has modest predictive ability in unfavourable early stage patients. Modification of the IPS for use with early stages may improve its prognostic power.
Adolescent↗
Is escalated BEACOPP a standard therapy for advanced Hodgkin's disease?
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Antineoplastic Combined Chemotherapy Protocols↗
A tale of two syndromes: ovarian hyperstimulation and abdominal compartment.
Abdominal compartment syndrome complicated severe ovarian hyperstimulation in a 35 year old woman with multiple bowel resections due to Crohn's disease. Pain from ovarian enlargement necessitated hospital admission. Despite intravenous fluid administration and heparin prophylaxis, ilio-femoral deep vein thrombosis developed. Treatment by intravenous heparin was complicated by repeated intra-ovarian bleeding, anaemia and acute renal failure requiring haemodialysis. Intra-abdominal pressures were elevated. After placement of an inferior vena caval filter and discontinuation of heparin, there was slow spontaneous recovery without surgery.
Abdomen↗
Association of Burkitt's lymphoma with the Epstein-Barr virus in two developing countries.
The clinical presentation of Burkitt's lymphoma (BL) and it's association with the Epstein-Barr virus (EBV) varies in different geographic areas, BL in developing countries being "intermediate" between the sporadic and endemic types, both in it's clinical presentation and it's association with EBV, which varies from 25-80%. In this study we have analysed the clinical features, EBV association, subtype and prevalence of the deleted variant of the Latent Membrane Protein-1 (LMP-1) of EBV in forty-two cases from two developing countries- India (n = 25) and Argentina (n = 17). In both countries the abdomen was the site most commonly involved while jaw involvement was rare. EBV was detected by in-situ hybridization using the EBER-1 RNA probe. 47% of cases from Argentina and 80% of cases from India were EBER positive. EBV typing using EBNA-3C primers showed a predominance of Type A in both countries (India-13/16 and Argentina-(7/8)). The 30bp deletion of the LMP-1 gene was detected in all evaluated cases from Argentina while the wild type of the gene was seen in all the evaluable Indian cases. Our study highlights the similarities and differences in the clinical presentation and EBV association of BL in two developing countries and also indicates that the subtype of EBV and prevalence of the LMP-1 deletion may reflect the predominant subtype in a particular population.
Adolescent↗
Partners Community HealthCare Extranet (PCHInet): a business plan.
This article presents an edited version of the business plan for PCHInet, an extranet designed to further Partners HealthCare System's strategic objectives of integrating its physician community, reducing costs, improving the quality of care, and raising the level of service delivery to its medical staff.
Community Networks↗
Do children with Hodgkin's disease have a better prognosis than adults? Application of a generalised linear model to a systematic review of published results.
This investigation aimed to compare survival rates in paediatric and adult Hodgkin's disease using published results. When comparing results obtained in different studies and institutions it is important to explain, estimate and allow for heterogeneity between studies. This was attempted though systematic inclusion of a large number of published results, through modelling the influence of covariates on survival using a generalised linear model, and by estimation of both the sampling errors in the extracted survival rates and the heterogeneity between studies. A significant superiority of treatment results in paediatric institutions compared with adult institutions was demonstrated, allowing for differences in patient and treatment characteristics.
Adult↗
Occult vitamin D deficiency in postmenopausal US women with acute hip fracture.
CONTEXT: Low vitamin D levels may contribute to hip fractures in women, although limited data are available on vitamin D levels in US women admitted with acute hip fractures. OBJECTIVE: To determine whether postmenopausal women with hip fractures have low vitamin D and high parathyroid hormone levels compared with nonosteoporotic and osteoporotic women admitted for elective joint replacement. DESIGN: Comparative case series conducted between January 1995 and June 1998. SETTING AND PATIENTS: Ninety-eight postmenopausal community-dwelling women with no secondary causes of bone loss admitted for hip replacement, of whom 30 women had acute hip fractures and 68 women were admitted for elective joint replacement. Of the women admitted for elective joint replacement, 17 had osteoporosis and 51 did not. Women with comorbid conditions or who were taking medications that affect bone density and turnover were excluded. MAIN OUTCOME MEASURES: Primary measures were levels of vitamin D and parathyroid hormone; secondary measures were body composition and markers of bone turnover. RESULTS: Women with hip fractures had lower levels of 25-hydroxyvitamin D than women without osteoporosis admitted for elective joint replacement (P = .02) and than women with osteoporosis admitted for elective joint replacement (P = .01) (medians, 32.4, 49.9, and 55.0 nmol/L, respectively; comparisons adjusted for age and estrogen intake). Parathyroid hormone levels were higher in women with fractures than women in the nonosteoporotic control group (P<.001) or than elective osteoporotic women (P = .001) (medians, 5.58, 3.26, and 3.79 pmol/L, respectively; comparisons adjusted for age and estrogen intake). Fifteen patients (50.0%) with hip fractures had deficient vitamin D levels (< or =30.0 nmol/L) and 11 (36.7%) had a parathyroid hormone level greater than 6.84 pmol/L. Levels of N-telopeptide, a marker of bone resorption, were greater in the women with hip fractures than in the elective nonosteoporotic controls (P = .004). CONCLUSIONS: Postmenopausal community-living women who presented with hip fracture showed occult vitamin D deficiency. Repletion of vitamin D and suppression of parathyroid hormone at the time of fracture may reduce future fracture risk and facilitate hip fracture repair. Because vitamin D deficiency is preventable, heightened awareness is necessary to ensure adequate vitamin D nutrition, particularly in northern latitudes.
Aged↗