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Biomedical subjects

A F Carpentier

Publications and source records attributed to A F Carpentier.

At least 19 recordsLinked to original sources
PubMed2006

Protein kinase Cgamma autoimmunity in paraneoplastic cerebellar degeneration and non-small-cell lung cancer.

BACKGROUND: The clinical and immunological profiles of patients with paraneoplastic cerebellar degeneration (PCD) and non-small-cell lung cancer (NSCLC) are not well known. OBJECTIVE: To review the clinical and immunological features of patients with PCD, NSCLC and without well-characterised onconeural antibodies. METHODS: The clinical features of nine patients with the diagnosis of classical PCD and NSCLC, included in our archives, were retrospectively reviewed. The presence of antibodies to cerebellar components was determined by immunohistochemistry and immunoblot of rat cerebellum. A cDNA library of human cerebellum was screened with the positive sera to identify the antigen. RESULTS: Nine patients with PCD and NSCLC were identified. Six patients were men, and the median age at diagnosis of PCD was 63 (range 47-73) years. PCD was completely reversed in two patients, and partially in one, after treatment of the tumour. The serum of one of the patients with PCD showed a unique reactivity with Purkinje cells. The screening of a cerebellar-expression library resulted in the isolation of protein kinase Cgamma (PKCgamma). PKCgamma immunoreactivity was not observed in the serum of 170 patients with non-paraneoplastic neurological syndromes, 27 patients with PCD, no onconeural antibodies and small-cell lung cancer, and 52 patients with NSCLC without paraneoplastic neurological syndromes. The NSCLC from 11 patients without PCD did not express PKCgamma at either the RNA or protein level. However, many cells of the NSCLC of the patient with PKCgamma antibodies expressed PKCgamma. CONCLUSION: PCD occurs in patients with NSCLC without typical onconeural antibodies and is associated with immune reactions against key proteins of the Purkinje cells.

Aged↗
PubMed2005

EGFR tyrosine kinase domain mutations in human gliomas.

Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor effective in patients with lung cancer with mutations in exons 19 and 21 of the EGFR tyrosine kinase domain. In this study, the authors tested the presence of such mutations in 95 gliomas including glioblastomas, anaplastic oligodendrogliomas, and low-grade gliomas. No mutation was found, which suggests that the biology of EGFR in gliomas is different from lung cancer and that this may be a factor in the resistance of glioblastomas to gefitinib.

Astrocytoma↗
PubMed2005

[New therapeutic approaches in glioblastomas].

INTRODUCTION: Current treatment of glioblastomas relies on surgical resection, radiotherapy and chemotherapy. However, the efficacy of these therapeutics is still limited and new therapeutic approaches based on the understanding of brain tumor biology are emerging. STATE OF ART: High expression of the EGF receptor by tumor cells, activation of the PI3K/Akt and the Ras/Raf pathways represent interesting targets for new selective drugs under development. Proteases inhibitors and antiangiogenic agents are also under investigations in clinical trials. Perspectives. In addition, the recent development of convection-enhanced delivery technique allows the administration of drugs which do not cross the blood-brain-barrier, such as selective toxins or immunostimulating oligonucleotides. CONCLUSION: Though the results of clinical trials have been somewhat disappointing, using different drug combinations or drug-radiotherapy associations will probably enable an improvement in the prognosis for these patients in the future.

Angiogenesis Inhibitors↗
PubMed2004

Value of Hu antibody determinations in the follow-up of paraneoplastic neurologic syndromes.

The long-term evolution of Hu antibody (Hu-Ab) titers in patients with paraneoplastic neurologic syndromes (PNSs) is not known. Described is the evolution of Hu-Ab titers in 35 patients with PNS with a median follow-up of 32 months (range 6 to 108 months). No correlation was observed between Hu-Ab titers and neurologic outcome, tumor evolution, or type of treatment. Serial Hu-Ab determinations are not useful for monitoring the clinical outcome of patients with PNS.

Adult↗
PubMed2004

Temozolomide as initial treatment for adults with low-grade oligodendrogliomas or oligoastrocytomas and correlation with chromosome 1p deletions.

PURPOSE: To determine the response rate of low-grade oligodendroglial tumors (LGOT) to temozolomide (TMZ) as initial treatment and to evaluate the predictive value of chromosome 1p deletion on the radiologic response. PATIENTS AND METHODS: Adult patients with pathologically proven LGOT with progressive disease on magnetic resonance imaging (MRI) were eligible for the study. TMZ was administered at the starting dose of 200 mg/m2/d for 5 days, repeated every 28 days. Response was evaluated clinically and by central review of MRIs. Chromosome 1p and 19q deletions were detected by the loss of heterozygosity technique. RESULTS: Sixty consecutive patients were included in the study. At the time of analysis, the median number of TMZ cycles delivered was 11. Clinically, 51% of patients improved, particularly those with uncontrolled epilepsy. The objective radiologic response rate was 31% (17% partial response and 14% minor response), whereas 61% of patients had stable disease and 8% experienced disease progression. The median time to maximum tumor response was 12 months (range, 5 to 20 months). Myelosuppression was the most frequent side effect, with grade 3 to 4 toxicity in 8% of patients. Loss of chromosome 1p was associated with objective tumor response (P < .004). CONCLUSION: TMZ is well tolerated and provides a substantial rate of response in LGOT. Chromosome 1p loss is correlated with radiographic response and could be a helpful marker for guiding therapeutic decision making in LGOT.

Adult↗
PubMed2003

European Organization for Research and Treatment of Cancer (EORTC) open label phase II study on glufosfamide administered as a 60-minute infusion every 3 weeks in recurrent glioblastoma multiforme.

BACKGROUND: Glufosfamide is a new alkylating agent in which the active metabolite of isophosphoramide mustard is covalently linked to beta-D-glucose to target the glucose transporter system and increase intracellular uptake in tumor cells. We investigated this drug in a multicenter prospective phase II trial in recurrent glioblastoma multiforme (GBM). PATIENTS AND METHODS: Eligible patients had recurrent GBM following surgery, radiotherapy and no more than one prior line of chemotherapy. Patients were treated with glufosfamide 5000 mg/m(2) administered as a 1-h intravenous infusion. Treatment success was defined as patients with either an objective response according to Macdonald's criteria or 6 months progression-free survival. Toxicity was assessed with the Common Toxicity Criteria (CTC) version 2.0. RESULTS: Thirty-one eligible patients were included. Toxicity was modest, the main clinically relevant toxicities being leukopenia (CTC grade >3 in five patients) and hepatotoxicity (in three patients). No responses were observed; one patient (3%; 95% confidence interval 0 to 17%) was free from progression at 6 months. Pharmacokinetic analysis showed a 15% decrease in area under the curve and glufosfamide clearance in patients treated with enzyme-inducing antiepileptic drugs, but no effect of these drugs on maximum concentration and plasma half-life. CONCLUSION: Glufosfamide did not show significant clinical antitumor activity in patients with recurrent GBM.

Adult↗
PubMed2001

Temozolomide chemotherapy in recurrent oligodendroglioma.

The authors determined the tolerance, response rate, and duration of recurrent anaplastic oligodendroglioma in 30 patients to temozolomide given orally at 150 to 200 mg/m2 on days 1 through 5 in cycles of 28 days. Nine patients responded: 7 of 27 patients (26%) treated with temozolomide after prior PCV chemotherapy and 2 of 3 chemotherapy-naive patients (both complete response). Median time to progression in responding patients was 13 months. Temozolomide shows promise and has an acceptable safety profile in recurrent anaplastic oligodendroglial tumors. Patients not responding to PCV may respond to temozolomide.

Adult↗
PubMed2001

Left ventricular reconstruction after resection of a large fibroma.

Cardiac fibromas are rare tumors that are histologically benign but potentially lethal because of their location. The prognosis is related to complete resection. We report the case of a 15-year-old boy who, 1 year after partial excision of a large fibroma, underwent successful complete resection through a conventional surgical approach with left ventricular reconstruction.

Adolescent↗
PubMed2001

Contralateral lung transplantation: a left lung implanted in the right thorax.

Since the inception of lung transplantation in 1982, it has been standard practice to implant donor lungs on the ipsilateral side in the recipient. The development of the techniques of lobar and bilateral lobar transplantation has shown that lung morphology may adapt to the shape of the thorax. Thus, variations in implantation have become possible. We describe a case of a 30-year-old man with severe bronchiectasis due to ciliary dyskinesis which required a left lower lobectomy at the age of 11 years and a left completion pneumonectomy 10 years later. His disease progressed and he was listed for a right lung transplantation. At the time of transplantation, the donor right lung was noted to be edematous and unfit for transplantation. This required grafting the donor left lung in the right thorax of the recipient. Follow-up at 7 years shows good exercise capacity and excellent functional tests without evidence of rejection.

Adult↗
PubMed2001

Cardiac arrhythmia in patients undergoing surgical repair of Ebstein's anomaly.

BACKGROUND: Arrhythmias remain an unsolved problem in Ebstein's anomaly. The aim of this study was to investigate the evolution of arrhythmias after surgical repair. METHODS: Forty-five patients with Ebstein's anomaly and arrhythmias were studied. Mean age was 33 +/- 15 years. Twenty-four patients (53%) had paroxysmal supraventricular tachycardia, 12 (27%) had atrial fibrillation or flutter, 8 (18%) had ventricular preexcitation (Wolff-Parkinson-White syndrome), and 1 (2%) had a nonsustained ventricular tachycardia. Surgical technique included detachment of the tricuspid anterior leaflet and suture on the atrioventricular annulus associated with right ventricular longitudinal plication. RESULTS: There were four hospital deaths (9%). A pacemaker was implanted early after operation in 5 patients (11%). During a mean follow-up of 57 +/- 50 months (range, 4 to 226 months), there were six additional deaths, three of which were sudden. Two patients were lost to follow-up. Of the 33 surviving patients, 8 (24%) continued to have symptomatic arrhythmias, and 15 (45%) were in permanent sinus rhythm. Of the 24 patients with preoperative paroxysmal supraventricular tachycardia and the 12 with atrial fibrillation or flutter preoperatively, 9 and 2 of the survivors, respectively, have had no further episodes of arrhythmia. The incidence of arrhythmia with or without symptoms was reduced to 39% (13/33) of the surviving patients. CONCLUSIONS: Arrhythmia is not totally abolished after operation. However, patients with Ebstein's anomaly and arrhythmia show substantial improvement after conservative surgical intervention.

Adolescent↗
PubMed2001

Implication of macrophages in tumor rejection induced by CpG-oligodeoxynucleotides without antigen.

Phosphorothioate oligodeoxynucleotides containing CpG motifs (CpG-ODNs) display broad immunostimulating activity and have potential applications in cancer immunotherapy. To investigate the antitumor activity of CpG-ODNs and to study the role of macrophages and lymphocytes in tumor rejection, CpG-ODN's effects on 9 L glioma cells were assessed in Fisher rats, depleted or not in macrophages, in nude mice, and in SCID mice. In nondepleted rats, intratumoral injections with 100 microg of CpG-ODNs on days 5, 12, and 19, after s.c. 9 L cell inoculations, resulted in an 84% reduction of the tumor volumes, when compared with controls injected with saline (P < 0.0001). Whereas all control animals developed tumors, more than one-third of the treated rats remained tumor free. Rejection of established glioma induced a specific long-term immunity, as cured rats were protected against a subsequent 9 L injection, but not a RG2 cell inoculation, another syngenic glioma in Fischer rats. Macrophages played a critical role in the early phase of tumor rejection, because the CpG-ODN's effects were significantly decreased in the rats depleted in macrophages, and none of the macrophage-depleted rats treated with CpG-ODNs rejected the tumor. On the contrary, both nude and SCID mice, which have normal innate immunity, showed a significant decrease of tumor volume when treated with CpG-ODNs when compared with controls. T cells were however involved in a later phase of the tumor rejection, as all nude mice eventually developed tumors despite the initial tumor growth inhibition. Altogether, these data suggest that immunostimulatory CpG-ODNs induced tumor rejections through an early activation of innate immunity and priming of a specific immune response against glioma cells.

Adjuvants, Immunologic↗
PubMed2001

[Cerebral glioblastomas and systemic metastases].

Glioblastomas are highly malignant but locally invasive tumors. In only rare instances do extra-neural metastasis occur. We report herein 2 cases of such dissemination occurring 9 and 15 month after the initial diagnosis and treatment of supratentorial gliomas. Metastasis involved the lung, the kidney and the liver in one case and the bones in the other case. Both patients died within 3 month after diagnosis of the systemic metastasis despite chemotherapy.

Bone Neoplasms↗
PubMed2000

Model of complete separation of the hepatic veins from the systemic venous system.

BACKGROUND: In patients undergoing a Fontan operation, partial diversion of the hepatic veins to the pulmonary venous atrium has been tried with various techniques. They failed because of the development of intrahepatic collaterals leading to an unacceptable right-to-left shunting. We postulate that to avoid the formation of intrahepatic collaterals, the totality of the liver has to be drained into the same pressure compartment. We have designed a model of cavopulmonary anastomosis in which a prosthetic conduit reproduces an azygos continuation, associated with the diversion of the totality of the hepatic venous return. This article reports on the early hemodynamics and the fate of the separation of the two venous compartments in long-term survivors. METHODS: Eighteen goats were operated on; the pulmonary artery and hepatic vein pressures were recorded. During month 2, an opacification of the inferior vena cava and the cavopulmonary connection was performed. Between months 6 and 14, another opacification was performed, together with pressure recording at both ends of the conduit. RESULTS: Postoperatively the pulmonary artery pressure was pulsatile with a mean of 10 mm Hg and the hepatic vein pressure was 0 mm Hg. The first angiogram showed patent tubes with fast progression of the contrast. Throughout the inferior vena cava injection, there was no opacification of the portal or hepatic veins. The late study showed a narrowed conduit in all animals. During the injection, a collateral was injected, feeding into the inferior mesenteric vein. No collateral circulation could be seen draining directly into the liver. The median gradient between the two ends of the conduit was 11 mm Hg. CONCLUSIONS: The isolation of the entire hepatic venous drainage is feasible and efficient for the separation of two pressure compartments. No intrahepatic collaterals are observed with this model at short- or long-term follow-up. The separation of the hepatic venous drainage should persist without collateral circulation as long as the inferior vena cava pressure stays at the levels observed in Fontan circulation.

Angiography↗