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Biomedical subjects

J L Bernard

Publications and source records attributed to J L Bernard.

At least 19 recordsLinked to original sources

[Infectious complications postengrafment in the first year after autologous stem cell transplantation in children].

BACKGROUND: Studies on the infectious complications postengrafment in pediatric stem cell transplantation patients are rare. The aim of this study was to assess the incidence, types, outcome and factors affecting late infections. PATIENTS AND METHODS: A single-institution retrospective analysis was done of infections recorded in the first year following engrafment in children who underwent autologous stem cell transplantation for solid tumors from January 1991 to December 2000. A systematic antimicrobial chemoprophylaxis of TMP/SMX was administered. Patients who were at high risk for varicella-zona virus infection received prophylactic acyclovir. RESULTS: Eighty-four assessable patients were enrolled. Fifty-four patients (64%) underwent autologous peripheral blood stem cell transplantation and 30 patients (36%) underwent bone marrow transplantation. Forty-nine episodes of infections were documented in 39 patients (46%) of whom 27 patients (32%) developed infections after the first 100 days post transplantation. Bacterial septicemia occurred in nine patients of whom four patients had a catheter-related septicemia. Twelve patients (14%) developed localized herpes zoster infection. Local fungal infection occurred in five patients. Infection-related death occurred in one patient with non-documented pneumonitis. Univariable analysis showed a correlation between the CD34(+) cell dose <7.5 10(6)/kg and the development of infections (P =0.04). Patients who did not go into remission after transplantation where at high risk for septicemia (P =0.007). Multivariate analysis showed that a history of varicella or pretransplant varicella-zona positivity was the only significant factor for development zoster infection (P =0.01). CONCLUSION: Our study shows that infections in the first year postengrafment following autologous stem cell transplantation for solid tumors have a good prognosis and that the use of TMP/SMX should be the single systematic antimicrobial prophylaxis. The CD34(+) cell dose seems to play a role in preventing late infections.

Adolescent↗

Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study.

PURPOSE: The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival. PATIENTS AND METHODS: A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded. RESULTS: The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P <.001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators. CONCLUSION: The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.

Adolescent↗

Anatomy of the presacral venous plexus: implications for rectal surgery.

The presacral venous plexus results from anastomoses between the lateral and median sacral veins, and courses into the pelvic fascia covering the anterior aspect of the body of the sacrum. The presacral venous plexus is not directly visible during rectal surgery, and injuries to this plexus may be life-threatening. Dissection of the retrorectal plane or anchoring of the rectum to the sacral promontory as in rectal prolapse surgery exposes the patient to the risk of injury to the presacral venous plexus. The aim of this study was to identify some avascular areas in the anterior aspect of the sacrum in order to lower the occurrence of such injuries during rectal surgery. The pelvis of 10 fresh cadavers was dissected after injection of a colored resin into the inferior vena cava, and the presacral venous plexus was studied. Four avascular tetragonal areas were common to all the specimens. The corners of a square with a side of 3 cm, centered on the anterior aspect of the body of sacrum, were always contained in the avascular areas. The upper side of this square was parallel to a line passing through the sacral promontory, at a 3 cm distance from it. Staples or sutures should be placed in the avascular areas to avoid injuries to the presacral venous plexus.

Cadaver↗

The LMCE5 unselected cohort of 25 children consecutively diagnosed with untreated stage 4 neuroblastoma over 1 year at diagnosis.

The Lyon-Marseille-Curie-Est (LMCE) of France cooperative group has previously reported successive series of unselected stage four children older than 1 year at diagnosis with metastatic neuroblastoma (LMCE 1 and 3). The goal of LMCE 5 study was to increase progression free survival rate as compared to LMCE 1 and 3. Based on improvements reported with post induction chemotherapy, the LMCE 5 used post induction for all children, but omitted total body irradiation and immunomagnetic purging in megatherapy regimen for all children. Twenty-five sequentially diagnosed children received an induction regimen which compared with previous induction included an increased dose of etoposide and cyclophosphamide, delivered similar dose of cisplatinum, and deleted doxorubicin and vincristin. After surgery treatment was stratified based on response and eligible children received etoposide carboplatin (LMCE 5A : n=10)+/-doxorubicin (LMCE 5B-C n=13) followed by megatherapy (melphalan without total body irradiation and unpurged peripheral blood stem cell rescue). The increase in drug doses during induction did not improve remission rate. The progression free survival at 6 years is 8%. It is significantly worse than LMCE 3, and equivalent to LMCE 1 study though toxic death rate has decreased with increasing experience. Failure to improve the response rate during induction and reducing the megatherapy regimen may be the main factors in this disappointing result. Modified strategies for induction, non toxic alternative to total body irradiation, and post megatherapy regimen should be developed.

Adolescent↗

Mechanisms governing subcellular localization and function of human RGS2.

RGS proteins negatively regulate heterotrimeric G proteins at the plasma membrane. RGS2-GFP localizes to the nucleus, plasma membrane, and cytoplasm of HEK293 cells. Expression of activated G(q) increased RGS2 association with the plasma membrane and decreased accumulation in the nucleus, suggesting that signal-induced redistribution may regulate RGS2 function. Thus, we identified and characterized a conserved N-terminal domain in RGS2 that is necessary and sufficient for plasma membrane localization. Mutational and biophysical analyses indicated that this domain is an amphipathic alpha-helix that binds vesicles containing acidic phospholipids. However, the plasma membrane targeting function of the amphipathic helical domain did not appear to be essential for RGS2 to attenuate signaling by activated G(q). Nevertheless, truncation mutants indicated that the N terminus is essential, potentially serving as a scaffold that binds receptors, signaling proteins, or nuclear components. Indeed, the RGS2 N terminus directs nuclear accumulation of GFP. Although RGS2 possesses a nuclear targeting motif, it lacks a nuclear import signal and enters the nucleus by passive diffusion. Nuclear accumulation of RGS2 does not limit its ability to attenuate G(q) signaling, because excluding RGS2 from the nucleus was without effect. RGS2 may nonetheless regulate signaling or other processes in the nucleus.

Amino Acid Sequence↗

Evaluation of micronucleated lymphocytes, constitutional karyotypes and anti-p53 antibodies in 21 children with various malignancies.

The implication of environmental carcinogens in childhood cancer is still unknown. To assess a possible link between DNA damage and alterations of the tumor suppressor gene p53, blood samples of 21 children with malignancies were examined for the presence of micronuclei in lymphocytes using the cytokinesis blocked micronucleus assay (CBMA). The constitutional karyotypes were analyzed for chromosome abnormalities and the presence of anti-p53 antibodies in blood sera was evaluated by an enzyme-linked immuno sorbent assay (ELISA). A control group of 20 children was also included. The rates of micronucleated cells were 5.1 per thousand+/-3.9 and 2.4 per thousand+/-2.3 for the cancer and control groups, respectively. The difference between the groups were statistically significant (P<0.05 by the Mann-Withney rank sum test). Two children in the cancer group showed extensive chromosome breakage in lymphocytes. The sera of two other children from the cancer group and of one child from the control group contained anti-p53 antibodies. Chromosome breakage and anti-p53 antibodies from the five children were associated with increased micronucleated cell rates. The results of the present study suggest that genotoxic events can occur in the lymphocytes of children with a cancerous state.

Adolescent↗

[Endometriosis of the rectus abdominis muscles].

The authors report three cases of endometriosis of the rectus abdominis muscle, presenting as a mass of the abdominal wall associated with pain during menstruation in women with a history of cesarean section. Treatment consisted in wide surgical resection followed by prosthetic abdominal wall repair in one recurrent case. Abdominal wall endometriosis is a rare disease that can be explained by grafting of endometrial cells to the abdominal wall during laparotomy for pelvic surgery, particularly cesarean section. Isolation of the abdominal wall during cesarean section and irrigation of the abdominal wall at the end of the operation are two theoretical measures designed to prevent endometrial cell engraftment. When abdominal wall endometriosis occurs, only radical surgical resection can prevent recurrence.

Abdominal Pain↗

LMCE3 treatment strategy: results in 99 consecutively diagnosed stage 4 neuroblastomas in children older than 1 year at diagnosis.

PURPOSE: To tailor postinduction therapy for stage 4 neuroblastoma in children who are older than 1 year at diagnosis according to status after induction. PATIENTS AND METHODS: From March 1987 to December 1992, 99 patients who were consecutively admitted were included in the Lyon-Marseille-Curie East of France (LMCE)3 strategy. After induction with the French Society of Pediatric Oncology NB87 regimen and surgery, patients who were in complete remission immediately proceeded to consolidation therapy with vincristine, melphalan, and fractionated total-body irradiation (VMT). All other patients underwent a postinduction strategy before VMT, either an additional megatherapy regimen or further chemotherapy with etoposide/carboplatin. RESULTS: The progression-free survival (PFS) is 29% at 7 years from diagnosis, which compares favorably with that of a similar cohort of 72 patients previously reported by our group (LMCE1; PFS of 20% at 5 years and 8% at 14 years, P =.004). In the multivariate analysis, only age younger than 3 years at diagnosis (P =.0085) and achievement of complete or very good partial remission after NB87 and surgery (P =.00024) remained significant. The PFS of the 87 patients who were included in the postinduction strategy was significantly better than that of the comparable 62 patients on the LMCE1 study (32% v 11% at 7 years; P =.005). CONCLUSION: The progressive improvements in the LMCE results over the last 10 years suggest that improvements in supportive care measures and increases in each component of this strategy (induction, postinduction, consolidation) may all contribute to increased survival rates.

Antineoplastic Combined Chemotherapy Protocols↗

G protein selectivity is a determinant of RGS2 function.

RGS (regulator of G protein signaling) proteins are GTPase-activating proteins that attenuate signaling by heterotrimeric G proteins. Whether the biological functions of RGS proteins are governed by quantitative differences in GTPase-activating protein activity toward various classes of Galpha subunits and how G protein selectivity is achieved by differences in RGS protein structure are largely unknown. Here we provide evidence indicating that the function of RGS2 is determined in part by differences in potency toward G(q) versus G(i) family members. RGS2 was 5-fold more potent than RGS4 as an inhibitor of G(q)-stimulated phosphoinositide hydrolysis in vivo. In contrast, RGS4 was 8-fold more potent than RGS2 as an inhibitor of G(i)-mediated signaling. RGS2 mutants were identified that display increased potency toward G(i) family members without affecting potency toward G(q). These mutations and the structure of RGS4-G(i)alpha(1) complexes suggest that RGS2-G(i)alpha interaction is unfavorable in part because of the geometry of the switch I binding pocket of RGS2 and a potential interaction between the alpha8-alpha9 loop of RGS2 and alphaA of G(i) class alpha subunits. The results suggest that the function of RGS2 relative to other RGS family members is governed in part by quantitative differences in activity toward different classes of Galpha subunits.

Amino Acid Sequence↗

[Adenocarcinoma in Barrett's esophagus. A study of 28 resected cases].

STUDY AIM: The aim of this retrospective study was to report a series of 28 patients with adenocarcinoma (ADK) arising in Barrett's esophagus (BE), treated by esophagectomy. PATIENTS AND METHODS: From 1992 to 1998, 28 patients were operated on for ADK in BE. There were 27 men and one woman (mean age: 65 years) classified as ASA I (n = 2), ASA II (n = 15) and ASA III (n = 11). Eighteen patients had a long story of gastro-esophageal reflux disease which required surgical repair in five of them. Dysphagia was the main symptom (n = 19). Surgical procedures included 15 Ivor Lewis operations, nine esophagectomies without thoracotomy and four esophagogastrectomies by the left thoracic approach. RESULTS: Pathological examination of the specimens showed an EBO with adenocarcinoma (n = 27) and a high grade dysplasia (n = 1). Among five patients with a previously known BE, three under endoscopic surveillance had high grade dysplasia (n = 1) and limited T1 tumor (n = 2), while the other two patients without surveillance developed an invasive tumor (T3N1). There were three postoperative deaths (mortality rate: 10%), all arising from pulmonary failure. Median survival was 16.6 months. All patients resumed a normal diet. The actuarial survival rates were 63%, 42% and 15.2% respectively at 1, 2 and 4 years. A multivariate analysis could identify 3 prognostic factors: ASA score previously known BE under surveillance, length of BE. CONCLUSION: Adenocarcinoma arising in BE is very often diagnosed too late. Patients with high risk BE require an endoscopic survey. High grade dysplasia detected in two successive examinations by two different pathologists may require prophylactic esophagectomy, but local endoscopic management presently under evaluation could be efficient in the future.

Actuarial Analysis↗

Effect of endoscopic sphincterotomy on bile lithogenicity in patients with gallbladder in situ.

BACKGROUND AND STUDY AIMS: Endoscopic sphincterotomy results in a continuous flow of bile into the duodenum and consequently leads to an increase in the frequency of enterohepatic bile acid cycling. Because bile acids are the driving force of biliary secretion, sphincterotomy may affect bile genesis. The present study was undertaken to determine the influence of endoscopic sphincterotomy on bile composition. PATIENTS AND METHODS: The cholesterol saturation index and the bile acid pattern were determined in the gallbladder bile of lithiasis patients with (group III) or without sphincterotomy (group I), and in the hepatic bile of patients with gallbladder in situ who were checked at 3 months after the endoscopic procedure (group II). Stones from each patient were examined for chemical composition and microstructure. RESULTS: All the patients had cholesterol stones. After endoscopic sphincterotomy the molar percentages of cholesterol in the gallbladder bile of group III and in the hepatic bile of group II were significantly lower (-31% and -46% respectively) than in group I. Similarly, the cholesterol saturation index in the hepatic bile (0.79) and the gallbladder bile (0.86) from patients who had undergone sphincterotomy indicated undersaturation whereas bile from group I was oversaturated (1.25). On the other hand, endoscopic sphincterotomy did not modify the hydrophobicity index of the bile acid pool, even though deoxycholate content increased. CONCLUSIONS: Endoscopic sphincterotomy causes a marked decrease in the lithogenicity of bile and thus may prevent the risk of recurrence of cholesterol lithiasis.

Absorptiometry, Photon↗

Clinical features of Behçet's disease in children: an international collaborative study of 86 cases.

OBJECTIVES: The objective of this study was to characterize the clinical picture of Behçet's disease (BD) in children. STUDY DESIGN: A questionnaire was completed by five BD specialists from Turkey, France, Iran, or Saudi Arabia. We first reviewed 86 cases retrospectively with a specially designed computerized database and then selected 65 who met the criteria of the International Study Group for BD, which include buccal aphthosis plus at least two among recurrent genital aphthosis, eye lesions, skin lesions, and positive pathergy test. The remaining 21 patients, who had features suggestive of BD but did not fulfill the international criteria, were analyzed separately and then compared with the other 65 patients. RESULTS: BD affected boys and girls equally. The clinical picture frequently included mucocutaneous lesions. Uveitis was less frequent than in adults but carried a poor prognosis, especially in male patients (p < 0.001). The mortality rate (3%) was related to large vessel involvement. Familial cases were particularly frequent (15%). Erythema nodosum and skin hypersensitivity were common in Turkish patients, whereas neuro-BD was more frequent in French and Saudi Arabian patients. Patients who did not fulfill the international criteria had significantly less genital aphthosis (p < 0.01), less skin lesions or hypersensitivity (p < 0.01), and less uveitis (p < 0.01). CONCLUSION: BD in children is similar to BD in adults. The high frequency of familial cases calls for further investigation of the immunogenetic factors that may favor early expression of the disease.

Adolescent↗

[Refractory pain in children with cancer: role of peridural analgesia].

BACKGROUND: Adequate treatment of pain in children with cancer is a critical issue, and is of equal importance as discussions concerning chemotherapy, surgery and radiotherapy. OBJECTIVE: To evaluate the treatment of refractory pain by peridural analgesia. METHODS: Seven children (1-15 years) with solid tumors were treated with long term epidural analgesia for refractory pain. Catheters were inserted in epidural space (L1-L2) and infused with sufentanil, bupivacaine and clonidine. RESULTS: Three out of five children with good response to peridural therapy could be discharged. A 12-month-old infant had a poor response. Treatment was discontinued in a teenager boy because of patient refusal. The side effects were: early catheter displacement in two patients and a bacterial contamination in one. Serious adverse effects related to high doses of opiates were not observed. However, toxicity of bupivacaine was observed in three patients leading to treatment discontinuation in one. CONCLUSION: Long-term epidural analgesia looks promising in selected children with refractory pain.

Adolescent↗