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Biomedical subjects

A F Carpentier

Publications and source records attributed to A F Carpentier.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Opsoclonus-myoclonus syndrome associated with non-metastatic neuroblastoma. Long-term survival. Study of the French Society of Pediatric Oncologists].

UNLABELLED: Opsoclonus-myoclonus is a rare syndrome characterized by multidirectional chaotic eye movements, myoclonus and ataxia. In children, it could be a paraneoplastic syndrome in association with neuroblastoma, usually with a high survival rate, but having a high frequency of neurologic and psychologic sequelae. OBJECTIVES: The aim of this study was to describe oncologic outcome (prospectively) and neurologic outcome (retrospectively) in children with non-metastatic neuroblastoma, and to determine its best treatment. PATIENTS AND METHODS: Data were collected on 21 children diagnosed with localized neuroblastoma and opsoclonus-myoclonus between 1990-1999 from the French Society of Pediatric Oncology institutions. RESULTS: Median age at diagnosis was 18 months. Location of the tumor was abdominal in 14 cases, thoracic in three cases, pelvic in three cases, and cervical in the last case. There was a majority of small tumors with a maximal diameter < 5 cm in 13 cases. Only four tumors were initially considered as unresectable tumors and received first-line chemotherapy. Complete macroscopic resection was performed in 20 cases (four after primary chemotherapy). Nine children received chemotherapy. Twenty children remained in first complete remission, and one relapsed and died (the unique NMYC amplified case). Treatment for opsoclonus-myoclonus varied widely. Only one child received no medical treatment for opsoclonus-myoclonus, because of complete resolution of neurologic symptoms after exclusive surgery. The following agents were used: corticosteroids in 18 cases, intravenously immune globulin in five cases, and antiepileptic drugs in seven cases. Ten patients experienced relapses of opsoclonus-myoclonus symptoms, mainly related to the decrease of steroid therapy (5/10). Ten of 16 assessable children had persistent neurologic deficits including speech delay or cognitive deficits (8/16), ataxia (6/16), motor delay (2/16), and behavioral problems (2/16). There is no correlation between neurologic outcome, and either age at diagnosis or duration of neurologic symptoms, or type of treatment of the tumor, particularly chemotherapy. CONCLUSION: Persistent neurologic deficits are characteristic for children with neuroblastoma and opsoclonus-myoclonus. Neurologic outcome seems unrelated to the treatment of neuroblastoma, which should exclusively be conducted according to oncological criteria. The treatment of opsoclonus-myoclonus should be standardized, mainly based on high-dose hydrocortisone, with a very low decreasing dosage, associated to intravenously immune globulin in severe cases. A biological immunologic work-up of the disease and cautious neurologic and psychologic standardized follow-up should be performed.

Adolescent↗
PubMed2000

[Corticosteroid-induced epidural lipomatosis].

Epidural lipomatosis is a rare disease, most often associated with chronic administration of exogenous steroids. We report the case of a 69-year-old man treated with 20mg prednisolone daily for 11 years because of polyarthritis. The patient complained of back pain associated with severe weakness of his lower limbs and brisk reflexes, with a progressive onset over one year. MRI showed epidural lipomatosis narrowing the epidural spaces from T-3 to T-10. Tapering of steroids was associated with slow but positive resolution of his symptoms.

Aged↗
PubMed2000

Successful treatment of intracranial gliomas in rat by oligodeoxynucleotides containing CpG motifs.

Phosphorothioate oligodeoxynucleotides with CpG motifs (CpG-ODNs) activate various immune cell subsets and induce production of numerous cytokines. To evaluate whether CpG-ODNs can induce rejection of established tumors, Lewis rats were inoculated intracerebrally with syngeneic CNS-1 glioma cells and subsequently injected with CpG-ODNs into the tumor bed. Although all of the control rats (n = 14) died within 23 days, 88% of the animals (n = 8) treated with a single CpG-ODN injection 5 days after tumor inoculation showed long-term survival (>90 days; P < 0.002). CpG-ODNs increased tumoral infiltration with macrophage/microglial cells, CD8, and natural killer lymphocytes. CpG-ODN-cured animals were further protected against a second tumor challenge. CpG-ODNs had no effect on a s.c. CNS1 tumor in nude mice, which suggested that CpG-ODN is not directly cytotoxic and that immunostimulation is required for the antitumoral effect. These findings suggest that intratumoral injections of CpG-ODNs represent a new immunotherapeutic approach in human gliomas, which overcome the need for the selection and purification of a tumoral antigen.

Animals↗
PubMed1999

Oligodeoxynucleotides containing CpG motifs can induce rejection of a neuroblastoma in mice.

Phosphorothioate oligodeoxynucleotides with CpG motifs (CpG-ODNs) activate various immune cell subsets and induce production of numerous cytokines. To evaluate whether CpG-ODNs can induce rejection of established malignant tumor, A/J mice were challenged by the s.c. implantation of a syngenic neuroblastoma cell line (neuro2a) and subsequently injected with CpG-ODNs in the vicinity of the tumor. Daily injections of 10 microg CpG-ODNs for 15 days seemed to be the most potent regimen, leading to the eradication of 5-mm-diameter tumors in one-half of the animals and a significant tumor growth inhibition when compared with controls (88% reduction volume; P<0.001). CpG-ODN-cured animals were further protected against a new tumor challenge. The antitumoral effect of CpG-ODNs was dependent on CpG motifs, and natural killer cells seemed to play a critical role in tumor rejection. We conclude that immunostimulatory CpG-ODNs may induce the rejection of established tumors and warrant further evaluation as a potential immunotherapeutic agent.

Adjuvants, Immunologic↗
PubMed1999

P/Q-type voltage-gated calcium channel antibodies in paraneoplastic disorders of the central nervous system.

Whether P/Q-type voltage-gated calcium channel (VGCC) antibodies are present in the serum of patients with paraneoplastic syndromes other than the Lambert-Eaton myasthenic syndrome (LEMS) and tumors other than small-cell lung cancer (SCLC) is controversial. Using a commercially available radioimmunoprecipitation assay kit, we examined the sera of 93 patients with paraneoplastic syndromes of the central nervous system (CNS), including 27 patients with paraneoplastic cerebellar degeneration (PCD) associated with tumors other than SCLC and 66 SCLC patients with paraneoplastic encephalomyelitis and sensory neuronopathy (PEM/SN). All PCD sera from patients with tumors other than SCLC were negative for P/Q-type VGCC antibodies. Eight of 66 (12%) SCLC patients with PEM/SN had P/Q-type VGCC antibodies; 4 had LEMS and the other 4 had no symptoms of LEMS or they were overlooked and, therefore, not examined electrophysiologically. In patients with paraneoplastic syndromes of the CNS, the detection of P/Q-type VGCC antibodies supports the diagnosis of LEMS; in our series, only 6% of patients with SCLC and PEM/SN may have had a false positive antibody result, or undiagnosed LEMS.

Autoantibodies↗
PubMed1999

Decreasing occupational risk related to blood-borne viruses in cardiovascular surgery in Paris, France.

BACKGROUND: Surgeons face the risk of patient-to-physician transmission of blood-borne viruses. This risk is related to the seroprevalence of the viruses in the patient population. METHODS: The seroprevalence of the human immunodeficiency virus, hepatitis B virus, and hepatitis C virus were determined in cardiovascular patients at Hôpital Broussais in Paris, France, over a 5-year period (1994 to 1998). RESULTS: Hepatitis C virus is the most prevalent virus in the patient population, whereas human immunodeficiency virus is the least frequent. The seroprevalence of hepatitis C virus and human immunodeficiency virus has decreased over time, whereas hepatitis B virus has remained constant. We apply the seroprevalence data to a mathematical model to estimate the occupational risk of seroconversion faced by surgeons over the length of their career. Our results show that the principal risk faced by the surgeon arises from hepatitis B virus and hepatitis C virus. The decreasing seroprevalence of the hepatitis C virus has resulted in a decrease in the occupational risk. CONCLUSIONS: The probability of becoming infected with a blood-borne virus over the career of the surgeon is notable. The greatest occupational risk to the surgeon is from the hepatitis viruses and not HIV.

Adolescent↗
PubMed1998

Surgical management of mitral regurgitation associated with Marfan's syndrome.

BACKGROUND: The surgical treatment of mitral regurgitation associated with Marfan's syndrome remains controversial because of the underlying degenerative process. METHODS: From October 1986 to June 1996, 33 patients with Marfan's syndrome underwent a mitral valve procedure. The mean age was 30 years (range, 2 to 55 years). Mitral regurgitation was caused by annulus dilatation in 2 patients, leaflet prolapse in 30 patients, and restricted leaflet motion in 1 patient. Mitral valve repair was performed in all patients except 1 who had mitral valve replacement. RESULTS: Two patients died in the perioperative period. All survivors were available for follow-up, which ranged from 1 month to 122 months (mean follow-up, 39 months). There were three late deaths, two of which were related to aortic complications. The actuarial survival rate was 78.9% at 10 years. Freedom from mitral valve reoperation was 87.1% at 10 years. Echocardiographic studies were obtained in all survivors and showed absent or mild (1+) mitral regurgitation in 21 patients and moderate (2+) mitral regurgitation in 3. CONCLUSIONS: Mitral valve repair for mitral regurgitation in patients with Marfan's syndrome can be performed safely in almost all instances. This technique provided stable midterm results comparable with those obtained for other degenerative mitral valve diseases.

Actuarial Analysis↗
PubMed1998

Effects of cardioplegic solutions on the vasoreactivity of the internal mammary artery.

BACKGROUND: During free internal mammary artery grafting, cardioplegia administration can be performed through the internal mammary artery. The present study examined whether cardioplegic solutions produce arterial graft constriction and functional endothelial damage. METHODS: Forty internal mammary artery segments from 10 patients were incubated in Krebs solution (n=10), University of Wisconsin solution (n=10), Broussais Hospital solution (n=10), or blood cardioplegia (n=10). RESULTS: There was a significant difference in sensitivity to norepinephrine between segments in Krebs solution and those in University of Wisconsin solution or Broussais Hospital solution but not segments in blood cardioplegia. There was a significant difference in relaxation to acetylcholine between segments in Krebs solution and those in the three other cardioplegic solutions and between those in blood cardioplegia and segments in University of Wisconsin solution or Broussais Hospital solution. There was no significant difference in relaxation to sodium nitroprusside between segments in any of the solutions. CONCLUSIONS: These experiments suggest that storage in the different cardioplegic solutions studied does not preserve the initial vasoreactivity of the internal mammary artery. However, blood cardioplegia appears to be less deleterious in regard to endothelial and myogenic vascular function.

Acetylcholine↗
PubMed1998

Heat treatment mitigates calcification of valvular bioprostheses.

BACKGROUND: Several techniques have been proposed to mitigate calcification of glutaraldehyde-preserved bioprostheses. None has been fully satisfactory. Knowing that heat induces significant molecular changes, we investigated the potential benefit of the heat treatment of glutaraldehyde-fixed tissues. METHODS: Samples of porcine valves and bovine pericardium treated in 0.625% glutaraldehyde were submitted to temperatures from 37 degrees to 70 degrees C for 2 to 12 weeks and then implanted subcutaneously in newborn rats for 3 months. In a second protocol, nine heat-treated porcine valve bioprostheses and seven control porcine valve bioprostheses were implanted in the mitral position in sheep for 20 weeks. RESULTS: Spectrophotometry and x-ray analysis comparing heat-treated versus non-heat-treated tissues showed the following: porcine valve: 6.7+/-2.3 microg Ca/mg (n = 8) versus 239.9+/-2.9 /g Ca/mg (n = 8); bovine pericardium: 19.5+/-8 microg Ca/mg (n = 6) versus 108+/-10.3 microg Ca/mg (n = 8); and porcine valve bioprostheses: 0 versus ++. CONCLUSIONS: Heat treatment of glutaraldehyde-treated bioprostheses significantly mitigated calcification in both subcutaneous and mitral position.

Animals↗
PubMed1998

Infrared spectroscopy in the evaluation of the process of calcification of valvular bioprostheses.

BACKGROUND: The methods currently used to analyze the process of calcification of bioprostheses give only global information on calcium deposition. We investigated the potential advantage of infrared spectroscopy, which makes it possible to analyze the various components of the calcification process, ie, lipids, proteins, and calcium deposits. METHODS: Sixty porcine aortic leaflets were fixed in 0.6% glutaraldehyde and then subsequently implanted in 10-day-old Wistar rats. The valve leaflets were removed 2, 7, 14, 21, 35, and 56 days after implantation. RESULTS: Before implantation infrared spectroscopic analysis revealed the presence of proteins only. On day 2 after implantation, all valves showed minor lipid deposits. On day 7, amorphous calcium phosphate was detected. Between days 7 and 14, crystalline forms of calcium phosphate appeared and amorphous calcium phosphate progressively changed into carbapatite over the 56-day period. CONCLUSIONS: Infrared spectroscopy yields valuable additional information on the nature and kinetics of the various components of glutaraldehyde-treated tissues after implantation. It may prove to be important in the evaluation of new techniques of calcium mitigation.

Animals↗
PubMed1998

DNA vaccination with HuD inhibits growth of a neuroblastoma in mice.

Some patients with small cell lung cancer (SCLC) or neuroblastoma develop an immune response against HuD, a human homologue of the Drosophila protein, elav, which is expressed in the nucleus and to a lesser degree the cytoplasm of neurons and tumor cells. This immune response is characterized by antibodies (anti-Hu) that at high titers are associated with a disease called paraneoplastic encephalomyelitis/sensory neuronopathy, in which infiltrates of T cells are found in the tumor and nervous system. Although all SCLCs express HuD, anti-Hu antibodies are identified in only 17% of patients with SCLC, usually at low titers, and are associated with indolent tumor growth. To determine whether the anti-Hu immune response causes indolent tumor growth, we developed an animal model using HuD DNA immunization. We found that a plasmid coding for a secreted form of HuD induced a strong and specific anti-Hu response. Immunized animals were challenged by s.c. implantation of a neuroblastoma cell line that constitutively expresses HuD. When compared with controls, mice immunized with the secreted HuD showed significant tumor growth inhibition (51% reduction volume; P = 0.0012), and 14% of them had complete tumor rejection. Tumors from these animals showed three times more CD3+ lymphocytic infiltrates than those from control mice and had a higher CD8+:CD4+ ratio. None of the animals developed neurological deficits or neuropathological evidence of nervous system pathology. In this mouse model of neuroblastoma, DNA immunization with HuD resulted in tumor growth inhibition but did not induce neurological disease. This model closely mimics the clinical course of more indolent tumor growth seen in patients with the anti-Hu immune response.

Animals↗
PubMed1997

Combined heart-lung-liver, double lung-liver, and isolated liver transplantation for cystic fibrosis in children.

Between June 1990 and September 1995, 8 of 24 children with cystic fibrosis (CF) who were accepted either for combined transplantation or isolated liver transplantation died while waiting for a graft; 11 underwent transplantation and 5 are currently on the waiting list. Of the 11 children who had surgery, 7 (group 1) underwent one of the following procedures: heart-lung-liver (n = 4), sequential double lung-liver (n = 2), or bilateral lobar lung from a split left lung and reduced liver (n = 1). During the same period, the four other children (group 2) underwent isolated liver transplantation (three full-size livers, one partial liver). There was one perioperative death in each group. Pulmonary infection was the most common cause of morbidity in group 1. Other complications in group 1 included tracheobronchial stenosis (n = 2), biliary stricture (n = 2), and severe ascites (n = 2). All were successfully treated. Obliterative bronchiolitis developed in three patients. This was treated with FK 506. In group 2, pulmonary function tests improved or remained stable after liver transplantation. Surgical complications in group 2 included severe ascites (n = 1), biliary stricture (n = 1), and abscess of the liver (n = 1). Actuarial survival was 85.7% +/- 2% in group 1 at 1 year; it remained unchanged at 3 years and was 64.2% at 5 years.

Adolescent↗
PubMed1997

Pulmonary bipartitioning and lobar transplantation: a new approach to donor organ shortage.

The scarcity of small donors has significantly limited lung transplantation for pediatric and small adult patients. Use of single lobes procured from size-unmatched donors has overcome this difficulty, but only in a few selected cases and, in addition, it represents a waste of lung tissue. In an animal model we have shown that it is possible to divide one lung with careful partitioning of the vascular and bronchial structures and thus obtain two viable lobar grafts suitable for bilateral implantation in a smaller animal. We have now applied this procedure clinically in seven patients operated on between May 1993 and November 1994. The indications were cystic fibrosis in three children, primary pulmonary hypertension in two adults, bronchiectasis in one, and idiopathic pulmonary fibrosis in one. There were three children aged 13 to 17 years (median 14) and four adults aged 40 to 53 years (median 45). There was a 46% to 50% discrepancy for weight between recipient and donor and a 12% to 17% discrepancy for height. The surgical technique consisted of careful partitioning of the left donor lung, bilateral anterior thoracotomy in the recipient, and, with the use of cardiopulmonary bypass, implantation of the lower lobe in the left hemithorax and the upper lobe in the right hemithorax. Vascular and bronchial connections were facilitated by leaving a long pedicle on the recipient side. The pulmonary artery anastomosis for the donor left upper lobe was done with the "fissure" side of the artery to ensure an anastomosis without tension. An end-to-end bronchial anastomosis overcame the problem of size discrepancy. Six patients are alive and well 10 to 27 months (median 19) after operation. One patient with cystic fibrosis died of systemic aspergillosis infection. All were discharged from the hospital within the first or second postoperative month. No technical problems were identified: repeated bronchoscopy has demonstrated satisfactory healing without early stricture formation. All patients remain well subjectively with good exercise tolerance and all patients achieve greater than 70% of predicted values of forced expiratory volume in 1 second. Perfect adaptation of the transplanted lobes to the recipient pleural space has been demonstrated by postoperative computed tomographic scan. In conclusion, bilateral lobar transplantation from a single donor lung is possible in small adults or children when there is a large size discrepancy with the donor. This may help resolve the problem of donor availability in the pediatric population.

Adolescent↗
PubMed1996

[Immunological diagnosis of paraneoplastic neurologic syndromes].

Paraneoplasic neurological syndromes are defined as an association between neurological disease and cancer in the absence of metastatic, infectious or metabolic complications. These syndromes occur in less than 1% of patients with cancer. With the exception of the Lambert-Eaton syndrome in which an autoimmune mechanism has been proven, the pathogenesis of paraneoplasic neurological syndromes remains unknown despite a frequent association with anti-Hu, anti-Yo, and anti-Ri antibodies. Neither passive transfer of these antibodies nor immunization with recombinant proteins has been able to produce paraneoplasic syndromes in animal models. It is most likely that cell immunity or other antigenic mechanisms are also implicated and that the synthesis of anti-Hu, anti-Yo or anti-Ri is simply one manifestation of a more complex immune reaction. Nevertheless, the discovery of these antibodies can be useful in the diagnosis of cancer, especially in the early stages. Other antibodies, specific for paraneoplasic neurological syndromes, will undoubtedly be discovered in the future, increasing the capacity of immunological diagnosis. A better understanding of immune cross reactions between the tumor and the nervous system may help further our understanding of the immune system and lead to progress in specific treatment for paraneoplasic neurological syndromes.

Autoantibodies↗
PubMed1996

Association of latissimus dorsi muscle expansion with electrostimulation before cardiomyoplasty.

BACKGROUND: The principle of cardiomyoplasty is chronic electrostimulation of the latissimus dorsi muscle (LDM) flap wrapped around the heart to obtain a phasic activity that can be integrated to ventricular kinetics. In clinical cardiomyoplasty procedures, a complete wrap of both ventricles by the LDM cannot always be obtained in cases of extremely dilated hearts. This is due to the limited LDM length available for wrapping. In most of these cases, benefits of cardiomyoplasty are very limited. We have investigated the feasibility of progressive LDM expansion associated with electrostimulation. The aim was to increase the muscle area before cardiomyoplasty, while preserving the electrophysiologic characteristics of muscle fibers. METHODS: In 5 goats, a silicone LDM expander with two incorporated muscular pacing electrodes was inserted deep into the LDM through a paravertebral incision along the posterior edge of the muscle. The pacing leads were connected to a myostimulator implanted in a subcutaneous pocket. The expander was progressively inflated over 8 weeks, up to 500 mL. Simultaneously the LDM was electrostimulated. RESULTS: At 2 months planimetric studies demonstrated an increase of the LDM surface from 175 +/- 12 to 229 +/- 17 cm2 (+31% +/- 4%; p < 0.05). The expanded LDM showed preserved electrophysiologic characteristics. The analysis of biopsy samples revealed histologic integrity of muscle fibers and preservation of their mean diameter. CONCLUSIONS: Potential benefits of this procedure are (1) increase of muscle surface, (2) training of muscular fibers and preservation of muscular tone, and (3) division of the distal vascular supply at implantation, which may potentiate vascularization from the LDM main pedicle. An LDM expansion could be considered before cardiomyoplasty in cases of significant heart dilatation. This device was successfully implanted in 2 patients, 2 months before cardiomyoplasty. Cardiomyoplasties were performed without difficulty, and a complete biventricular wrap was obtained in both patients in spite of massive cardiomegaly.

Animals↗
PubMed1996

Aortomyoplasty counterpulsation: experimental results and early clinical experience.

BACKGROUND: Presently the only clinical method of skeletal muscle augmentation of the heart is achieved by wrapping muscle around the cardiac ventricles and then stimulating the muscle to contract synchronously with cardiac systole. Intraaortic balloon counterpulsation provides diastolic counterpulsation in the short-term with the known benefits of increasing diastolic pressure and reducing ventricular afterload. Using protocols already in existence for dynamic cardiomyoplasty we have investigated the long-term use of extraaortic skeletal muscle-powered counterpulsation. METHODS: In five alpine goats the right latissimus dorsi muscle (LDM) was used to achieve a wrap around the ascending aorta, which had been augmented with an elliptic pericardial patch. Electrostimulation protocols were commenced after 2 weeks and continued for 12 to 24 months. At this time baseline hemodynamic measurements were made with and without stimulation of the LDM. Acute cardiac depression was induced and further measurements were made, again with and without stimulation of the LDM. RESULTS: Results in the basal state demonstrated improvement in all parameters with stimulation and a 23% increase of the subendocardial viability index. After induction of cardiac depression there was a 52% increase in cardiac output, 39% decrease in systemic vascular resistance, and 27% increase in subendocardial viability index. Histologic studies demonstrated tight adhesion between the aortic wall and the LDM, no dilatation of the aortic wall, and no deleterious effects in the aortic wall of the chronic intermittent constriction. Histochemical staining demonstrated transformation of the muscle fibers of the LDM flap into type 1 oxidative muscle fibers. CONCLUSIONS: In conclusion, our present study demonstrates that in this animal model aortomyoplasty produces a chronic counterpulsation with preservation of aortic architecture. With induction of heart failure aortomyoplasty provided an effective means of cardiac assistance. The use of the ascending aorta to achieve diastolic counterpulsation may be an efficient use of skeletal muscle energy to augment the heart in selected clinical cases. Early clinical experience is described in this article.

Animals↗