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Biomedical subjects

M Hebbar

Publications and source records attributed to M Hebbar.

At least 19 recordsLinked to original sources
PubMed2006

Phase II study of an optimized 5-fluorouracil-oxaliplatin strategy (OPTIMOX2) with celecoxib in metastatic colorectal cancer: a GERCOR study.

BACKGROUND: Oxaliplatin stop and go in combination with leucovorin and 5-fluorouracil has been successfully used in a previous study (OPTIMOX1) in metastatic colorectal cancer (MCR). Celecoxib is an anti-cyclooxygenase-2 drug with anti-neoplastic properties. In the present study, celecoxib was evaluated in combination with FOLFOX7 regimen and as a single agent in maintenance therapy. PATIENTS AND METHODS: This phase II study examined for previously untreated MCR patients the stop-and-go procedure [six cycles of folinic acid, 5FU and oxaliplatin (FOLFOX7) followed by chemotherapy-free intervals (CFIs) and reintroduction at progression] with continuous administration of celecoxib (800 mg/day). RESULTS: Forty-four patients were included, 42 eligible: performance status (%) 0/1/2=45/40/15, median age 60 (31-76) years. Response rate (RR) was 43% (95% CI 28%-58%). Median progression-free survival (PFS) was 6 months; median overall survival was 15.8 months. Grade 3/4 toxicity criteria were neurotoxicity 9.5%, thrombocytopenia 21.4%, neutropenia 7.1%, diarrhea 7.1%, nausea 4.8% and vomiting 2.4%. Median CFI 1 (n=27) duration was 3.9 months (range 2-39 months). CONCLUSION: With an acceptable safety profile, celecoxib combined with FOLFOX7 achieved RR and PFS in the lower range of that obtained with FOLFOX7 alone. These results indicate the lack of synergy between FOLFOX7 and celecoxib. PFS of 6 months appears lower than PFS obtained in OPTIMOX1 study with simplified LV5FU2 in maintenance therapy.

Adult↗
PubMed2006

'A phase II study of oral uracil/ftorafur (UFT) plus leucovorin combined with oxaliplatin (TEGAFOX) as first-line treatment in patients with metastatic colorectal cancer'.

This phase II trial was performed to evaluate the efficacy and tolerability of a new combination of Uracil/Ftorafur (UFT)/leucovorin (LV) and oxaliplatin in patients (pts) with metastatic colorectal cancer (MCRC) who had not received prior chemotherapy for metastatic disease. Between February 2002 and October 2002, 64 patients received UFT 300 mg m(-2) day(-1) and LV 90 mg day(-1) from day 1 to day 14 combined with oxaliplatin 130 mg m(-2) on day 1, every 3 weeks. All patients were evaluable for safety analysis and 58 of 64 patients were eligible for efficacy. Responses were reviewed by an independent review committee. Of the 58 per-protocol defined assessable patients, 1 complete response and 20 partial responses were observed yielding a response rate of 34% (95% CI: 22-47). The median response duration was 8.74 months (range 1.6-14). The median time to progression and the median survival were 5.88 months (95% CI: 4.34-8.21) and 18.2 months (95% CI: 10-20.7), respectively. Diarrhoea and peripheral neuropathy were the most frequent and predictable toxicities. These events were reversible, noncumulative and manageable. Grade 3 diarrhoea occurred in only 11% of the patients. No grade 4 gastrointestinal toxicity was reported in the study. The incidence of grade 3/4 (National Cancer Institute Common Toxicity Criteria 2: NCI-CTC 2) peripheral neuropathy was 15%. Haematological toxicity was of mild to moderate intensity with 10% of the patients with Grade 3/4 neutropenia without any episode of complication. The TEGAFOX regimen, a new combination using UFT/LV and oxaliplatin every 3 weeks is feasible on an outpatient basis. The combination is safe and active and may offer a promising alternative to the intravenous route. Nevertheless this efficacy results should be confirmed by randomized phase III trials.

Administration, Oral↗
PubMed2005

A phase II trial of raltitrexed (Tomudex) in advanced pancreatic and biliary carcinoma.

PURPOSE: To evaluate the impact of raltitrexed (Tomudex) on the quality of life in a multicenter, phase II study in advanced pancreatic and biliary carcinomas. PATIENTS AND METHODS: Forty-six patients with advanced, histologically proven pancreatic (n = 37, 80.4%) or biliary (n = 9, 19.6%) carcinoma received 3 mg/m2 raltitrexed intravenously once every 3 weeks. For the quality of life assessments, EORTC QLQ-C30 was used, and the evaluation of the clinical benefit was performed according to the 4 criteria of the clinical benefit response. All patients were assessed for safety, and 41 patients were evaluable for objective response. RESULTS: Patients (63% male/37% female) had a mean age of 61.2 years, 71.7% had a PS of 0-1, 78.3% had metastatic disease, and 63% had at least 2 tumoral sites. A total of 176 cycles were administered with a mean of 4 cycles per patient (range 1-12). Three out of 43 patients evaluable for EORTC QLQ-C30 (7.0%; CI(95%) 1.4-19.0%) had a quality of life improvement. Thirty-two patients fulfilled the 4 criteria required to evaluate the clinical benefit response; 5 were responders (15.6%; CI(95%) 5.3-32.8%); 1 patient was a good responder based on both the EORTC questionnaire and the clinical benefit response. Forty-one patients were assessable for response, 3 responded to treatment (response rate: 6.5 %; CI(95%) 1.3-17.9%). Median survival was 4.6 months (CI(95%) 2.9-8.2 months), the 1-year survival rate was 21.8%. The most common grade 3-4 toxicities were neutropenia (8%), leukopenia (8%), thrombopenia (6%), anemia (6%), liver enzyme elevations (11%), asthenia (9%), vomiting (9%), abdominal pain (7%), and phlebitis (6%). One treatment-related death occurred (neutropenic sepsis). CONCLUSION: Raltitrexed appeared to be generally well tolerated and showed a clinical benefit response and/or quality of life improvement in a limited number of patients.

Antimetabolites, Antineoplastic↗
PubMed2005

Prospective evaluation of the impact of [18F]fluoro-2-deoxy-D-glucose positron emission tomography of resectable colorectal liver metastases.

BACKGROUND: The aim of this study was to assess the additional value of information provided by positron emission tomography (PET) with [(18)F]fluoro-2-deoxy-D-glucose (FDG) over that provided by computed tomography (CT) in patients with resectable liver metastases from colorectal cancer. METHODS: Between October 2001 and November 2002, a prospective double-blind comparison of preoperative FDG-PET and thoracoabdominal CT was performed in 53 patients with potentially resectable liver metastases from colorectal cancer. All resected metastases were subjected to histological examination. RESULTS: Histological examination confirmed the presence of malignant or benign lesions detected by PET and/or CT in 95 per cent of instances. Overall sensitivity (78 per cent) and accuracy (88 per cent) of PET were equivalent to those of CT (76 and 86 per cent respectively). The sensitivity of PET was equivalent to that of CT for hepatic sites (both 79 per cent), but was superior for extrahepatic abdominal sites (63 and 25 per cent respectively). PET provided additional information in five patients, mainly by revealing abdominal extrahepatic metastases, but falsely upstaged three patients. CONCLUSION: Whole-body FDG-PET may identify unrecognized extrahepatic metastases in patients with potentially resectable liver metastases imaged by CT. However, additional information provided by PET is not as reliable as suggested by earlier retrospective studies.

Adult↗
PubMed2004

Detection of circulating soluble CD28 in patients with systemic lupus erythematosus, primary Sjögren's syndrome and systemic sclerosis.

The aim of this study was to evaluate the presence and the role of the serum soluble costimulatory molecule CD28 in patients with systemic lupus erythematosus (SLE), primary Sjögren's syndrome (SS), and systemic sclerosis (SSc). Soluble CD28 concentration was determined by ELISA in 45 patients with SLE, 45 patients with primary SS, 30 patients with SSc, and 45 healthy subjects. We also evaluated CD28 mRNA expression by semiquantitative RT-PCR, and the biological activity of recombinant soluble CD28 on T lymphocyte activity. Concentrations of soluble CD28 were significantly higher in patients with SLE, primary SS and SSc than in healthy subjects. Soluble CD28 concentrations were higher in patients with systemic primary SS than in patients with glandular-limited primary SS. PCR analysis suggested that soluble CD28 resulted from the shedding of the membrane form. In vitro assay revealed that soluble CD28 inhibits the anti-CD3 mAb induced T cell proliferation. Soluble CD28, which modulates the proliferation of T lymphocytes, could be associated with disease severity in patients with autoimmune disease, especially primary SS. These results suggest that soluble CD28 could play an important role in the regulation of autoimmune diseases.

Adolescent↗
PubMed2004

Antiphospholipid antibodies in primary Sjögren's syndrome: prevalence and clinical significance in a series of 74 patients.

The aim of this study is to determine prevalence, clinical significance of antiphospholipid antibodies (aPL) including anticardiolipin antibodies (aCL), anti-beta2GP1 and lupus anticoagulant (LA) in a cohort of 74 patients with primary Sjögren's syndrome (pSS) according to revised European criteria. aPL were found in 25 (34%) patients; IgG in 23 (12 had low titres, six moderate titres and five high titres) and IgM in five (three and two had respectively moderate and high titres). Eight (11%) patients were found to have LA; anti-beta2GP1 antibodies were detected only in three (4%) patients. Only two patients with LA, aPL and beta2GP1 had recurrent venous thrombosis. One patient with moderate titres of aPL exhibited recurrent spontaneous foetal losses. Peripheral neuropathies without cryoglobulinemia were more frequent in the aPL group. Other systemic involvements of pSS were the same in both groups with or without aPL. Patients with aPL have more concurrent immunological diseases such as thyroiditis and primary biliary cirrhosis and a higher prevalence of hypergammaglobulinemia (P < 0.05). Even if aPL prevalence reached 30% in pSS, titres were usually low, with a close correlation with hypergammaglobulinemia but not with antiphospholipid syndrome, which is related to positivity of both LA and aPL.

Adult↗
PubMed2004

[Standards, Options and Recommendations 2004: good practice guidelines for second opinion in anatomic and surgical pathology in oncology (integral report)].

CONTEXT: The " Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the French Federation of Cancer Centres (FNCLCC), the 20 French Regional Cancer Centres, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVE: To develop good practice guidelines for second opinion in anatomic and surgical pathology in oncology, in collaboration with the French Society for Anatomic and Surgical Pathology. METHOD: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs using the definitions of the Standards, Options and Recommendations project. Once the guideline has been defined, the document is submitted to independent reviewers for review. RESULTS: The working group defined four types of second opinions in anatomic and surgical pathology: personal consultation, inter-institutional consultation, peer review consultation for a scientific survey, intra-departmental consultation in the context of quality control. The main recommendation is that second opinion should respect the patients' rights and the medical ethics code. For each of the four situations defined recommendations have been developed, taking this principle into consideration.

Ethics, Medical↗
PubMed2002

[Systemic sclerosis and pregnancy].

PURPOSE: Pregnancy in a patient with systemic sclerosis (SSc) may pose a double problem to the medical team: influence of SSc on pregnancy and consequences of pregnancy to SSc manifestations. CURRENT KNOWLEDGE AND KEY POINTS: Concepts have evolved. SSc was considered for a long time not only as not very propitious for pregnancy but also as a strict contraindication for procreation because risks for the mother and the baby were thought to be major. Currently, fertility is thought to be normal. Miscarriages and small-for-gestation age infants rate do not seem to be higher in SSc. Maternal and perinatal mortality is also not higher in SSc without severe visceral manifestations, i.e. without either pulmonary hypertension, or cardiac or respiratory insufficiency. Conversely, there is a significantly higher frequency of premature infants in SSc. As regards influence of pregnancy on SSc, the greatest fear is the occurrence of renal crisis, which may be life threatening for both mother and child. Each elevation of blood pressure, even if this increase is mild, should be considered as potentially very serious. However, pregnancy itself does not seem to increase the risk of renal crisis. Consequences of pregnancy to SSc manifestations are various but usually mild. FUTURE PROSPECTS AND PROJECTS: SSc is not a strict contraindication for pregnancy only if severe organ involvement, diffuse subset of SSc or recent onset of the disease has been ruled out. Physicians should be aware of specific problems, which SSc is possibly posing during pregnancy. Finally, it has been recently suggested that pregnancies could be involved in the pathogenesis of SSc through persisting microchimerism of fetal origin.

Acute Disease↗
PubMed2002

[Psychiatric complications of corticoid therapy in the elderly over 65 years of age treated for Horton disease].

OBJECTIVES: To analyse steroid psychiatric related complications in aged (> 65 years old) with temporal arteritis (TA). METHODS: Retrospective cohort study. PATIENTS: In a cohort of 126 elderly patients with a diagnosis of TA and followed with a mean period of 64 months, clinical and biological presentations, outcome and corticoid adverse effects were recorded throughout the follow-up period. RESULTS: Twenty patients (16%), (mean age: 73 +/- 7.9 years, male n = 6) exhibited corticosteroid related psychiatric complications. Symptoms appear to be dose dependent and generally begin during the first month of treatment. Psychiatric disorders were as follow: mood disturbances (n = 8), depression (n = 6), mania (n = 3), anxiety neurosis (n = 2) and dementia (n = 1). Three patients were hospitalized in psychiatric units and 2 in nursing home. Psychiatric adverse affects appears to be more frequent with prednisone than prednisolone (P < 0.05).

Aged↗
PubMed2001

Expression of nerve growth factor receptors and their prognostic value in human breast cancer.

Nerve growth factor (NGF) has been shown recently to be mitogenic for human breast cancer cells. In the present study, we have assayed the expression of NGF receptors (NGFRs: TrkA and p75) mRNAs in 363 human primary breast cancers, using real-time quantitative reverse transcription-PCR. NGFRs were found in all of the tumor biopsies. TrkA and p75 were positively correlated and were respectively associated with the histoprognostic grading and the tumor type. NGFRs were both related to progesterone receptors. In univariate analyses, TrkA (>upper quartile) was associated with longer overall survival. Histoprognostic grading, tumor size, node involvement, and steroid receptors were also prognostic factors. In Cox multivariate analyses, TrkA was not a prognostic parameter. This study demonstrates the expression of NGFRs in breast cancer and points out that patients with high levels of TrkA have a more favorable overall survival prognosis.

Adult↗
PubMed2001

[Wegener's granulomatosis in the elderly patient].

PURPOSE: To determine aged-related variations in clinical and biological presentation and outcome in Wegener's granulomatosis. METHODS: In a retrospective cohort study of 35 patients with a diagnosis of Wegener's granulomatosis, 24 patients (69%) younger than 60 years of age and 11 (31%) aged 60 years or older were compared for clinical and biological characteristics. RESULTS: Clinical presentation was the same in the two groups; lymphopenia was more common in the elderly group (P > 0.05). Despite a similar treatment regime, outcome was significantly worse for the elderly group (> or = 60 years), with a mortality rate of 36% versus 8% in the control group. Mortality was essentially due to delayed infectious complications, raising the problem of a less intensive immunosuppressive treatment after remission.

Adult↗
PubMed2001

[Pulmonary hypertension screening in systemic scleroderma: a cohort study of 67 patients].

PURPOSE: Pulmonary hypertension is a severe complication of systemic sclerosis and has emerged as a major cause of morbidity and mortality in this condition. Treatment is all the more efficient as pulmonary hypertension is early diagnosed. A good knowledge of the clinical, biological and functional features of pulmonary hypertension in systemic sclerosis is therefore necessary to suspect and to diagnose pulmonary hypertension as early as possible. METHODS: Sixty seven patients with systemic sclerosis were retrospectively studied. We compared clinical, immunological, functional (spirometry) and morphological (pulmonary fibrosis) features according to the presence (n = 25) and the characteristic of pulmonary hypertension (isolated or secondary) or the absence (n = 42) of pulmonary hypertension, assessed by Doppler echocardiography. RESULTS: CREST syndrome (calcinosis, Raynaud's phenomenon, oesophageal involvement, sclerodactyly and telangiectasia) was more frequent in patients with isolated pulmonary hypertension than in patients without PH (72.7% vs 28.5%, P < 0.05; odds-ratio [OR] = 6.6) and dyspnea was more severe (P < 0.001; OR = 11.4). The age at time of pulmonary hypertension diagnosis was higher in patients with secondary pulmonary hypertension than in patients with isolated from (median: 62.5 years (range: 32-35) vs 53 years (range: 37-85), P < 0.05). Patients with isolated pulmonary hypertension had anticardiolipin antibodies more frequently than patients without pulmonary hypertension (72.7% vs 35.7%, P < 0.05). Isolated reduction of diffusing capacity was preferentially observed among patients with isolated pulmonary hypertension than among those without pulmonary hypertension. A linear relation between systolic pulmonary artery pressure values and diffusing capacity values (r = 0.72, P < 0.01) was found. Isolated reduction of diffusing capacity was more frequent in patients with isolated pulmonary hypertension than in patients without pulmonary hypertension (63.6% vs 14.3%, P < 0.001; OR = 10.5). CONCLUSION: The severity of pulmonary hypertension in systemic sclerosis justifies a systematic screening by Doppler echocardiography and diffusing capacity measurement. Our results allow us to better define the characteristics of sclerodermic patients with isolated or secondary pulmonary hypertension. The search for pulmonary hypertension should be repeated with time and clinicians should be particularly vigilant in the case of a patient presenting these characteristics.

Adult↗
PubMed2001

Relationship between parity and clinical and biological features in patients with systemic sclerosis.

OBJECTIVE: To assess the influence of parity on the clinical and biological features of systemic sclerosis (SSc). METHODS: We recorded the following clinical and biological data of 100 consecutive women with SSc: age, disease duration before diagnosis, cutaneous extension of sclerosis according to LeRoy's classification, pulmonary involvement, and antinuclear antibodies. We compared these features to the number and sex of children who were born before SSc onset. Date of birth of the first children was systematically recorded. RESULTS: Patients with limited SSc had more children before SSc onset than patients with diffuse SSc (2.4 +/- 1.8 vs 1.7 +/- 1.5; p < 0.05). The interval between first birth and SSc onset was shorter for patients with limited SSc than for patients with diffuse SSc (11.0 +/- 9.9 vs 23.5 +/- 14.5 yrs; p < 0.01). Patients with pulmonary fibrosis had more children than patients without pulmonary fibrosis (2.5 +/- 1.9 vs 2.0 +/- 1.6; p < 0.05). Age at first birth was significantly higher when the child was a girl than a boy (26.8 +/- 7.5 vs 22.9 +/- 5.3 yrs; p < 0.05). The interval between the first birth and SSc onset was shorter when the child was a girl than a boy (16.2 +/- 9.6 vs 25.4 +/- 13.4 yrs; p < 0.05). CONCLUSION: Pregnancy related microchimerism could be preferentially associated with limited SSc and pulmonary fibrosis. Microchimerism may be facilitated in cases in which the fetus is female.

Adult↗
PubMed2001

Aerosolized iloprost in CREST syndrome related pulmonary hypertension.

OBJECTIVE: To assess the outcome of patients with CREST syndrome associated severe pulmonary hypertension treated by aerosolized iloprost in a noncomparative study. METHODS: Five patients with CREST syndrome associated severe pulmonary hypertension were treated with 100 microg/day of aerosolized iloprost. New York Heart Association functional class and exercise tolerance (6 min walk test) were assessed at baseline, after one month, and then every 6 months. A right heart catheterization was performed at baseline in all but one patient. Systolic pulmonary artery pressure (PAP) was measured with Doppler echocardiography after one month and every 6 months. RESULTS: The mean followup was 13.2 +/- 8.8 months (median 6, range 6-24). Subjective quality of life improved in all patients. NYHA functional class decreased from Class III to II in 3 patients, from Class III to I in one patient, and from Class IV to III in one patient. At 6 months, the distance walked in 6 min had increased from 352 +/- 48 to 437 +/- 56 m (p = 0.06). At one month the mean systolic PAP was 58 +/- 13 vs 81 +/- 9 mm Hg at baseline (p = 0.04). At 6 months the mean systolic PAP was 57 +/- 13 mm Hg (p = 0.06). The improvement of both clinical and hemodynamic status was maintained in the 2 patients treated for 2 years. Neither adverse effects nor need to increase the daily dose of iloprost were observed. One patient died of right heart failure and one patient did not experience any improvement of exercise tolerance and hemodynamics. CONCLUSION: Aerosolized iloprost might be potentially useful as treatment for CREST syndrome associated pulmonary hypertension. However, patients who could benefit from this treatment will probably have to undergo careful criteria selection.

Administration, Inhalation↗
PubMed2000

Increased concentrations of the circulating angiogenesis inhibitor endostatin in patients with systemic sclerosis.

OBJECTIVE: Endostatin is an angiogenesis inhibitor derived from type XVIII collagen. The aim of this study was to determine the concentrations of circulating endostatin in patients with systemic sclerosis (SSc), and to assess the relationship between these concentrations, extension of tissular sclerosis, and presence of cutaneous scars or ulcers. METHODS: The study involved 50 patients with SSc and 30 healthy subjects. Cutaneous extension of sclerosis was graded according to Barnett's classification system: 33 patients had grade I SSc and 17 patients had grades II or III SSc. The results of pulmonary function tests were abnormal in 31 of 50 patients, 8 of whom also had abnormalities on chest radiograms. Cutaneous scars or ulcers were found in 22 of 50 patients. Endostatin concentrations were determined using a competitive enzyme immunoassay method. RESULTS: The mean circulating endostatin concentration was significantly higher in the SSc group than in the healthy subjects group (mean +/- SD 53.2 +/- 22.4 ng/ml versus 9.9 +/- 9.7 ng/ml; P < 10(-4)), in patients with grade II or grade III SSc than in patients with grade I SSc (63.2 +/- 20.2 ng/ml versus 45.1 +/- 15.6 ng/ml; P < 10(-2)), in patients with abnormal findings on chest radiograms than in patients with normal findings on chest radiograms (67.6 +/- 22.4 ng/ml versus 50.4 +/- 21.6 ng/ml; P < 0.05), and in patients with cutaneous scars or ulcers than in patients without these manifestations (60.9 +/- 25.9 ng/ml versus 47.2 +/- 13.3 ng/ml; P < 10(-2)). CONCLUSION: Circulating endostatin concentrations are significantly increased in patients with SSc. Production of endostatin may result from tissular sclerosis and could contribute to the development of ischemic manifestations.

Adult↗
PubMed2000

Regulation of sialyltransferase expression by estradiol and 4-OH-tamoxifen in the human breast cancer cell MCF-7.

We have addressed the effects of estradiol and 4-OH-tamoxifen on the expression of five sialyltransferases in the hormono-dependent MCF-7 cell line using a Multiplex RT-PCR approach. Estradiol induced a statistically significant increase in ST3Gal III and a decrease in ST6Gal I, whereas the two other enzymes, ST3Gal IV and ST3Gal I, are not modified and expression of the fifth enzyme, ST3Gal II, was very low or not detectable. Estradiol effects were dose dependent and completely antagonized by 4OH-tamoxifen. In addition, there is no direct relation between cellular proliferation and sialyltransferase expression. This suggests that ST3Gal III and ST6Gal I could be used as supplementary markers of hormono-sensitivity in breast cancer.

Antineoplastic Agents, Hormonal↗
PubMed2000

[Bronchiolitis obliterans with organized pneumonia: a rare complication of primary Gougerot-Sjögren syndrome].

INTRODUCTION: Bronchiolitis obliterans organizing pneumonia (BOOP) is characterized by plugs of granulation tissue in bronchioles, alveolar ducts and alveoli. This pulmonary disorder has been reported in some cases in relation to drug consumption (D-penicillamine, amiodarone), with bacterial or viral infections (Mycoplasma pneumoniae, HIV), and with systemic diseases, such as rheumatoid arthritis. To our knowledge, only three cases of association BOOP-Sjögren's syndrome have been reported. EXEGESIS: We report three new cases of BOOP. These patients presented a primary Sjögren's syndrome without clinical or biological abnormalities suggestive of other autoimmune diseases. Initial presentation was an acute pulmonary disorder mimicking a bacterial pneumonia. Two patients had cutaneous vasculitis and the third vasculitic neuropathy. Corticosteroid therapy was begun and was quickly successful. None of the patients presented a relapse of BOOP. CONCLUSION: The incidence of BOOP is probably underestimated in patients with primary Sjögren's syndrome without cutaneous vasculitis. In case of pneumonia with antibiotic resistance, an immunological mechanism should be considered.

Adrenal Cortex Hormones↗