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J D Rain

Publications and source records attributed to J D Rain.

At least 19 recordsLinked to original sources
PubMed2001

In vivo model mimicking natural history of dog prostate cancer using DPC-1, a new canine prostate carcinoma cell line.

BACKGROUND: Dog prostate cancer is usually considered to be highly relevant to human prostate cancer. We report the isolation of a new canine prostate cancer epithelial cell line designated DPC-1. METHODS: Primary cultures were established from a canine poorly differentiated prostatic adenocarcinoma. Population doubling time was determined by counting nuclei after cell lysis. Tumorigenicity was assessed in nude mice and in one adult immunodeficient dog. Immunoscintigraphy was performed in both models using a monoclonal antibody (mAb) raised against the [44-62] sequence of human PSMA. RESULTS: DPC-1 cells have a rapid growth in vitro (doubling time, 27 hr) which is not stimulated by androgens. In addition, DPC-1 displays immunoreactivity to human PSA and PSMA. DPC-1 was found to be highly tumorigenic not only in nude mice but also for the first time after orthotopic seeding in an immunodeficient dog. This allograft mimicked, in a compressed form, the aggressive biological behavior of spontaneous dog prostate adenocarcinoma. Immunoscintigraphy using a (131)Iodine-labeled PSMA mAb clearly visualized induced tumors in nude mice and in the dog allograft. CONCLUSIONS: This study suggests that DPC-1 may constitute a powerful model for assessing new diagnostic and/or therapeutic tools in the management of prostate cancer.

Adenocarcinoma↗
PubMed2001

[Hydroxyurea--is it a harmless drug in Vaquez disease?]].

The frequent side effects of Hydroxy-Urea and the non-exceptional risk of leukemia and cancer in Polycythemia Vera treated for a long time by Hydroxy-Urea allow to conclude that Hydroxy-Urea is not an innocent drug. In a prospective trial of 150 patients with a median follow up of nine years, Hydroxy-Urea given alone induced side effects in 29% of patients necessitating to stop treatment in half of cases. The percentage of leukemia or myelodysplasia is 6.7% with an actuarial risk of leukemic transformation of 10% at 13 years. In an other prospective trial in 181 aged patients Hydroxy-Urea was given as maintenance therapy after 32P treatment. The median follow-up in that study is also of nine years. Side effects are observed in 13% of cases. A two fold increase of the leukemic risk was observed in the maintenance arm of the trial: 11 versus 19% at ten years, 14 vs 30% at 12 years, 16 vs 35% at 15 years because of the leukemogenic effect of Hydroxy-Urea in maintenance therapy we stopped including new patients in this arm of the trial.

Aged↗
PubMed2001

[18F]-FDG positron imaging in clinical management of lymphoma patients.

[18F]-FDG is a glucose analogue labelled with a short-lived positron emitter. During the past decade, it has been proposed to detect in vivo lymphoma lesions with PET, a new non-invasive imaging modality. We aimed at reviewing the current experience with FDG in several clinical settings of lymphoma. Due to the lack of specificity of FDG for lymphoma, histology remains compulsory to establish the diagnosis. Nevertheless, in the case of AIDS, FDG imaging has been proposed to differentiate lymphoma and opportunistic infections in brain lesions. To explore lymphoma extension, FDG-PET highlights more lesions than CT or the clinical examination and results in upstaging 13% of cases. It could also be used for selecting a site for biopsy when the location considered first clinically is difficult to access. Staging lymphoma with FDG-PET also provides baseline images for subsequent evaluation of therapy, which is one of the most promising indications: a negative scan predicts response to therapy and subsequent remission with a predictive value of 89%, and a positive scan either reflects resistance or predicts relapse with a predictive value of 83%. The current achievement of FDG imaging is the early detection of recurrence or of viable tissue in residual masses that remain several months after treatment. Both its sensitivity (84%) and its specificity (95%) overwhelm the values of conventional imaging, mainly CT and gallium-67 scintigraphy. When PET, as a new clinical imaging modality, is not yet widely demanded by clinicians and/or the number of FDG examinations is less than 500 per year, a 'hybrid' gamma-camera or CDET can be an alternative to dedicated PET. For 3 years, we have been using FDG-CDET in the 2D mode without attenuation correction, and obtained the following accuracy in a total of 40 examinations that could be evaluated: 85% for assessment of chemotherapy and 92% to detect recurrences and evaluate residual masses. Our preliminary results also stress the interest in FDG examination in childhood lymphoma, with the same indications as in adults.

Disease Management↗
PubMed2001

Iodine-131 ablation therapy for a patient receiving peritoneal dialysis.

The authors describe a patient with follicular thyroid carcinoma who was receiving continuous ambulatory peritoneal dialysis to manage end-stage renal disease. To deliver radioiodine therapy to ablate thyroid remnants safely and under optimal conditions, the behavior of 37 MBq (1 mCi) I-131 was followed daily for 3 days. Blood activity and total body count decreased with a half-life of 100 hours (4.17 days). The daily iodide removal rate, estimated as a percentage of the total administrated activity, was low: 5.3% to 8.6% in peritoneal dialysate and 1.3% to 2.2% in urine. The thyroid uptake, measured using a probe, was 2.4% to 2.1% from day 1 to day 3 and 1.9% later at day 8. The volume of thyroid remnants was determined by ultrasonography to be 0.6 g. The patient received a reduced ablative I-131 dose of 814 MBq (22 mCi). Radiation emitted from the patient after I-131 therapy, monitored using a radiation monitor probe located at a distance of 1 meter, decreased with an effective half-life of 70 hours (2.9 days). The integration of the curve from t = 0 showed a level always less than 25 microSv/hour as early as 24 hours after treatment. Because the iodine removal rate is continuous but low in a case of peritoneal dialysis, smaller therapeutic doses must be administered to deliver maximal radiation to residual thyroid tissue while minimizing excessive radiation exposure to patients, their families, and medical staff.

Carcinoma, Papillary, Follicular↗
PubMed2001

Thoracoscopy or CT-guided biopsy for residual intrathoracic masses after treatment of lymphoma.

BACKGROUND: An intrathoracic mass persists after completion of treatment in 20% of the patients treated for Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL). Gallium scan and positron emission tomography allow for diagnosis in most cases. However, in some patients, a pathologic examination of the residual mass (RM) is required. The aim of this study was to evaluate the results of a thoracoscopic approach for intrathoracic RM, as compared with image-guided biopsies. PATIENTS AND METHODS: From 1996 to 1998, 29 consecutive patients treated for NLH (n = 11) or HD (n = 18) were referred either to radiology (group R; n = 8) or to surgery (group S; n = 21) for biopsy of an intrathoracic RM. There were 13 male and 16 female patients ranging in age from 15 to 56 years (mean, 32 years). The reason for a biopsy was the inability to determine the nature of the RM by means of radiologic examination or scintigraphy. Biopsy was defined as successful when (1) residual lymphoma was found in the specimen, or (2) benign tissue was found and the patient remained disease-free after a minimal follow-up period of 12 months. A biopsy was defined as a failure when a local recurrence occurred in a patient with a diagnosis of benign lesion. RESULTS: No significant procedure-related complications occurred in either group. The mean follow-up was 26 months (range, 13 to 72 months). In group R, residual lymphoma was found in only one patient. In group S, residual lymphoma was found in seven patients (p = 0.5). In the seven patients of group R with a diagnosis of benign mediastinal lesion, two patients had a local recurrence and one had a recurrence within the abdomen. In the 15 patients of group S in whom no residual disease was found, 1 patient had an intrathoracic recurrence (p = 0.5) while 2 patients had recurrence in a remote site. CONCLUSION: Despite the limited number of patients in this series, results suggest that a thoracoscopic approach yields better data than image-guided biopsies.

Adolescent↗
PubMed2001

Intermethod discordance for alpha-fetoprotein measurements in Fanconi anemia.

BACKGROUND: The significantly higher serum alpha-fetoprotein (AFP) in patients with Fanconi anemia (FA) than in non-FA aplastic patients has potential diagnostic utility, but the increase is method-dependent. The aim of this study was to compare five AFP assays on FA and non-FA samples and to investigate possible explanations for FA-specific discrepancies. METHODS: Two methods available in our laboratory (Kryptor and IMx) were compared on 59 FA and 27 non-FA patient samples. Kryptor, Immulite, Elecsys, Immuno-I, and Elsa-2 methods were then compared on 14 FA and 14 non-FA patient samples. The AFP glycosylation profile was analyzed by electrophoretic separation in a lectin-containing gel. RESULTS: With all six methods, AFP values were significantly higher in FA than in non-FA patients, but the diagnostic precision and optimal cutoff values varied. Indeed, two methods reached 100% sensitivity and specificity, but in other methods, one or both of these parameters were significantly <100%. Neither heterophilic antibodies nor a specific glycosylation profile was detected in FA samples. CONCLUSIONS: AFP results are method-dependent in FA. New methods must be evaluated before use in differential diagnosis of aplastic patients.

Adolescent↗
PubMed2001

Is the thrombopoietin assay useful for differential diagnosis of thrombocytopenia? Analysis of a cohort of 160 patients with thrombocytopenia and defined platelet life span.

BACKGROUND: Thrombopoietin (TPO), the major hormone controlling platelet production, has been measured in thrombocytopenias with discordant results. The aim of our work was to assess the value of the TPO assay for differential diagnosis of thrombocytopenias in a large cohort of patients classified according to the results of their platelet isotopic study. METHODS: We measured TPO (R&D Systems) in serum of 160 thrombocytopenic patients referred to our department for platelet life span isotopic studies. We classified patients as follows: (a) idiopathic or autoimmune thrombocytopenia group (ITP; patients with increased platelet destruction and shortened platelet life span; n = 67); (b) pure genetic thrombocytopenia group (patients with decreased platelet production, normal platelet life span, and without bone marrow aplasia; n = 55); (c) bone marrow aplasia group (BM; patients with decreased platelet production, normal platelet life span, and bone marrow aplasia; n = 13). RESULTS: In patients with pure genetic thrombocytopenia, TPO (median, 55 ng/L) was not different from TPO in patients with ITP (median, 58 ng/L) or controls (n = 54; median, 51 ng/L). Only in patients with bone marrow aplasia was TPO significantly higher (median, 155 ng/L) and negatively correlated to the platelet count (r(2) = 0.5014). CONCLUSIONS: Although the median serum TPO is increased in thrombocytopenia with decreased platelet production from bone marrow aplasia, it does not differentiate patients with pure genetic thrombocytopenia from those with ITP.

Adolescent↗
PubMed2000

Constitutive elevation of serum alpha-fetoprotein in Fanconi anemia.

The diagnosis of Fanconi anemia (FA) is based on the association of congenital malformations, bone marrow failure syndrome, and hypersensitivity to chromosomal breaks induced by cross-linking agents. In the absence of typical features, the diagnosis is not easy to establish because there is no simple and cost-effective test; thus, investigators must rely on specialized analyses of chromosomal breaks. Because we observed elevated serum alpha-fetoprotein (sAFP) levels in FA patients, we investigated this parameter as a possible diagnostic tool. Serum AFP levels from 61 FA patients and 27 controls with acquired aplastic anemia or other inherited bone marrow failure syndromes were analyzed using a fluoroimmunoassay based on the TRACE technology. Serum AFP levels were significantly more elevated (P <.0001) in FA than in non-FA aplastic patients. In the detection of FA patients among patients with bone marrow failure syndromes, this assay had a sensitivity of 93% and a specificity of 100%. This elevation was not explained by liver abnormalities. Levels of sAFP were unchanged during at least 4 years of follow-up, and allogeneic bone marrow transplantation did not modify sAFP levels. Three of 4 FA patients with mosaicism as well as 5 of 6 FA patients with myelodysplastic syndrome were detected by this test. Heterozygous parents of FA patients had normal sAFP levels. Measurement of sAFP levels with this automated, cost-effective, and reproducible fluoroimmunoassay could be proposed for the preliminary diagnosis of FA whenever this disorder is suspected.

Adolescent↗
PubMed2000

Restaging with gallium scan identifies chemosensitive patients and predicts survival of poor-prognosis mediastinal Hodgkin's disease patients.

UNLABELLED: Following treatment of mediastinal Hodgkin's disease (HD), residual masses are frequent and gallium scanning has proven to be of value in the evaluation of their specificity (fibrosis or active disease). This study assessed, for relapse and survival, the predictive value of restaging gallium scan of patients with a residual mass on computed tomography scan after induction chemotherapy. Between 1/89 and 12/97, in 53 newly diagnosed HD patients with a residual mediastinal mass, a gallium scan was performed after chemotherapy (3 or 4 courses) and always before consolidative radiotherapy. Characteristics at diagnosis were: nodular sclerosis histology, 89%; bulky mediastinal disease, 79%; B-symptoms, 51%. RESULTS: gallium scan was positive in 16 patients (30%) and negative in 37 (70%). At median follow-up period of 36 months, freedom-from-progression rate was 86% versus 19% (P<0.0001) for patients with negative vs positive gallium scans, respectively. The 5-year overall survival (OS) rate was 68% and differed significantly (P<0.0001) between negative (91%) and positive (25%) gallium scanning groups. The specificity of gallium scanning was 91% and the sensitivity 72% with a positive predictive value of 81% and a negative predictive value of 86%. Evaluation with gallium scan after induction chemotherapy identifies chemosensitive patients among those with poor-prognosis mediastinal HD. Although relapse may occur in patients with negative gallium scan, a postive gallium scan is highly predictive of failure and poor outcome, and treatment should thus be modified.

Adult↗
PubMed2000

[Preservation of erythrocytes of heterozygous SC sickle cell patients].

In order to evaluate the feasibility of the autologous transfusion in an alloimmunized sickle cell patient, changes in the hematologic and biochemical characteristics of erythrocytes stored for 42 days from two patients with sickle cell SC anemia were compared with control subjects' (Hb A) red blood cells. Erythrocytes were stored in Saline Adenosine Dextrose Mannitol at +4 degrees C. The cryopreservation storage was made and 51Cr red cell survival was measured in one patient. No significant difference in the hematologic and biochemical parameters of the SC red blood cells and the control subjects was observed during the storage at +4 degrees C. Red cell survivals determined in fresh cells, cells stored for 42 days at +4 degrees C and thawed cells from one patient demonstrate much shorter half-life values than those of normal red blood cells. Before application, our results need to be confirmed by the same protocol with another patient with sickle cell SC.

Adenosine Triphosphate↗
PubMed2000

Quantitation of minimal residual disease in acute promyelocytic leukemia patients with t(15;17) translocation using real-time RT-PCR.

We took advantage of a recently developed system allowing performance of real-time quantitation of polymerase chain reaction to develop a quantitative method of measurement of PML-RARalpha transcripts which are hallmarks of acute promyelocytic leukemia (APL) with t(15;17) translocation. Indeed, although quantitation of minimal residual disease has proved to be useful in predicting clinical outcome in other leukemias such as chronic myeloid leukemia or acute lymphoblastic leukemia, no quantitative data have been provided in the case of APL. We present here a method for quantitation of the most frequent subtypes of t(15;17) transcripts (namely bcr1 and bcr3). One specific forward primer is used for each subtype in order to keep amplicon length under 200 bp. The expression of PML-RARalpha transcripts is normalized using the housekeeping porphobilinogen deaminase (PBGD) gene. This technique allows detection of 10 copies of PML-RARalpha or PBGD plasmids, and quantitation was efficient up to 100 copies. One t(15;17)-positive NB4 cell could be detected among 106 HL60 cells, although quantitation was efficient up to one cell among 105. Repeatability and reproducibility of the method were satisfying as intra- and inter-assay variation coefficients were not higher than 15%. The efficiency of the method was finally tested in patient samples, showing a decrease of the PML-RARalpha copy number during therapy, and an increase at the time of relapse.

Chromosomes, Human, Pair 15↗
PubMed2000

From guidelines to hospital practice: reducing inappropriate ordering of thyroid hormone and antibody tests.

OBJECTIVE: Because of major technical improvements and conscious care about cost effectiveness, limiting the inadequate use of thyroid biological tests appears to be a major issue. DESIGN: To (i) estimate the ordering prevalence of each thyroid test, (ii) assess the prevalence of relevant thyroid tests, and (iii) evaluate the impact of expressing justification for tests during a 2-month intervention period on these prevalences. METHODS: During a prospective 2-month survey (June-July 1997), all the request forms were divided into four groups of prescription: (1) investigation of thyroid function, (2) taking drugs affecting the thyroid, (3) monitoring of nodule and cancer, and (4) investigation of thyroid autoimmunity. Their appropriateness was thus determined according to consensus in our hospital and previously published recommendations. Results were compared with those of retrospective similar 2-month periods in 1996 and 1998. Combinations of thyroid function tests and thyroid antibodies were analyzed during the 1996, 1997 and 1998 periods. RESULTS: The overall estimated rate of appropriate ordering between 1996 and 1997 increased from 42.5% to 72.4% (P<10(-4)), with a significant improvement in each group of main diagnosis referral, except in group 3 where suitability was always over 85%. However, in group 4, appropriateness remained low (36%). Combinations of thyroid tests revealed an increase in single TSH order forms and single autoantibodies to thyroperoxidase (TPOAb) ones, while TSH+free thyroxine+free tri-iodothyronine and TPOAb+ autoantibodies to thyroglobulin ones decreased significantly. Interestingly, all these changes were maintained 1 year later (June-July 1998) even though physicians were not aware of this new study. CONCLUSIONS: Persistent change in medical practice was thus assessed.

Autoantibodies↗
PubMed2000

Diagnosis and treatment of polycythemia vera and possible future study designs of the PVSG.

The present study describes clinicopathological criteria to distinguish the 5 sequential stages proposed by Wasserman et al in the natural history of newly diagnosed PV patients. The European Working Group on MPD (EWG.MPD) extended and modified the PVSG diagnostic criteria of PV by including bone marrow histopathology. From the results of prospective randomized studies in PV it became evident that new clinical trials in previously untreated PV patients should focus on comparing interferon-alpha, a non-leukemogenic approach, versus a potential leukemogenic myelosuppressive treatment modality. Hydroxyurea appears to be the least leukemogenic myelosuppressive agent in long-term prospective clinical PV-studies extending observation periods of more than 10 years. The rational for using IFN-alpha as a first-line treatment option in newly diagnosed PV-patient include its effectiveness to abate constitutional symptoms and to induce a complete remission thereby avoiding phlebotomy, iron deficiency, and macrocytosis associated with hydroxyurea. Moreover IFN-alpha may prevent or delay the development of postpolycythemic myelofibrosis if used early in the course of the disease. Clinicians will be reluctant to postpone the use of hydroxyurea in early stage PV as long as a conservative approach using phlebotomy aiming at a hematocrit below 0.45, plus low-dose aspirin for the control platelet function or anagrelide for the control platelet number is used to keep the patient healthy. Low-dose aspirin will prevent the microvascular thrombotic complications of thrombocythemia associated with PV in remission after phlebotomy, but lacks myelosuppressive activity. Control of megakaryocyte maturation and reduction of platelet production to normal (<400 x 10(9)/l) by relatively low doses of anagrelide will predict a significant reduction of vascular complications in the early stages of PV, may prevent progression to myelofibrosis during follow-up of PV and very probable will postpone the use of hydroxyurea treatment for controlling the platelet count in PV. Large scale randomized clinical trials in PV are proposed, which should aim not only for clinical and hematological response, safety, efficacy, but should also assess toxicity, the need for phlebotomy and whether the development of progressive disease such as splenomegaly, pruritus, myelofibrotic myeloid metaplasia, spent phase, myelodysplasia and acute leukemia can be delayed or prevented by IFN-alpha as compared to a conservative approach of phlebotomy plus low-dose aspirin or anagrelide followed by hydroxyurea when signs of myeloproliferative activity became evident.

Blood Platelets↗
PubMed1999

Cervicomediastinal magnetic resonance imaging in persistent or recurrent papillary thyroid carcinoma: clinical use and limits.

Cervicomediastinal magnetic resonance imaging (MRI) was evaluated in 13 consecutive persistent or recurrent papillary thyroid carcinoma (PTC) patients, previously treated by total thyroidectomy and radioiodine ablation. All had elevated thyroglobulin (Tg) levels and were therefore submitted to a new therapeutic radioiodine dose followed by a posttherapeutic whole-body scan (131I-WBS) and subsequent MRI. Patients with known distant metastases were excluded from the study. Group 1 included 7 patients with a negative 131I-WBS, whereas cervical and/or mediastinal 131I-uptake was evidenced in the other 6 patients (group 2). MRI was thus compared to 131I-WBS, and additionally in 8 reoperated cases, to histology. MRI was positive in 11 of 13 (85%) patients, corresponding to 23 of 55 (41.8%) histologically confirmed sites. In group 1, MRI was positive in 5 of 7 patients, with a sensitivity of 47% (15/32 histologically positive sites), allowing appropriate indication of surgery: 4 neck surgery, and 1 mediastinal dissection because of too distant lymph node foci. In group 2, MRI always showed more localization than 131I-WBS; histology was obtained in 3. Because all the foci located in the mediastinal area (0.8 to 1.8 cm) were histologically confirmed (7/7 sites), MRI avoided underestimation of surgery in the 8 reoperated patients. However, additional images were also observed corresponding to a normal thymus, a small neuroma or inflammatory lymph nodes, but pretracheal and very small nodes (less than 0.5 cm) were missed. In conclusion, although less specific than radioiodine scintigraphy, MRI can detect local persistent or recurrent PTC, and seems particularly effective for evaluation of mediastinal involvement.

Carcinoma, Papillary↗
PubMed1998

[Treatment of polycythemia. I--Using radiophosphorus with or without treatment in 483 patients over 65 years of age].

AIMS: To compare by a prospective study in high risk polycythemia vera (PV) patients 33P alone and 32P followed by low-dose hydroxyurea (HU) maintenance therapy. Toxicity, efficiency, and leukemogenic potential were studied. PATIENTS: 483 patients with a documented PV, aged more than 65 years at diagnosis, were included between 1980 and 1996 in a prospective study comparing 32P alone and 32P followed by low-dose HU maintenance therapy. Blood cell counts were performed every two months and a clinical evaluation by a specialist was obtained every four or six months. RESULTS: Treatments were well tolerated, but chronic leg ulcers were observed in the maintenance therapy arm. The risk of leukemia was about 15% at the 15th year in the group of patients treated by 32P alone, but reached 30% in the group receiving maintenance therapy. In both arms, there was no significant correlation between occurrence of leukemia and the total dose of 32P. There was a correlation between the leukemic risk and disease severity, estimated on the frequency of relapse. Cancer occurrence was slightly higher than expected in the maintenance arm. HU treatment did not protect against progression to myelofibrosis, probably due to the lack of maintenance of an efficient myeloid or megakaryocytic suppression. Median life-span was slightly shorter in the group receiving HU maintenance. In all cases, life-span was only one year lower than that observed in the reference population. CONCLUSION: For all these reasons, we suggest the us of 32P alone in elderly patients; complementary chemotherapy should only be prescribed in the cases with short-term relapse, and late resistance to 32P.

Aged↗
PubMed1998

[Treatment of polycythemia. II.--Comparison of hydroxyurea with pipobroman in 294 patients less than 65 years of age].

AIMS: To compare by a prospective study in low risk polycythemia vera (PV) patients alone two drugs: hydroxyurea and pipobroman. Toxicity, efficiency, and leukemogenic potential were studied. PATIENTS: 294 patients with a documented PV, aged less than 65 years, have been included since 1980 in a prospective study comparing hydroxyurea and pipobroman. Blood cell counts were performed every two months and a clinical evaluation by a specialist was obtained every four or six months. RESULTS: Hematologic toxicity of both drugs was higher than expected, requiring strict surveillance. These drugs were tolerated in some (gastric pain and diarrhea on pipobroman, buccal aphtosis and chronic leg ulcers on hydroxyurea), leading to a change of arm in 10% of the cases. Hydroxyurea did not control the megakaryocitic hyperplasia in 40% of the cases, which probably explains a high rate of progression to myelofibrosis with myeloid metaplasia in this arm. Both drugs were leukemogenic with an actuarial risk of about 15% at the 15th year, not significantly lower than that observed in the 32P treated patients. A significant risk of cutaneous malignancy was observed in the hydroxyurea arm. The mean expectancy of life cannot yet be accurately evaluated, but seems significantly lower than that of the reference population. CONCLUSION: The treatment of PV by hydroxyurea or pipobroman has to account for these results less optimistic than those traditionally well-known to hematologists and internists.

Adult↗