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Biomedical subjects

P Simon

Publications and source records attributed to P Simon.

At least 163 records · Page 9Linked to original sources

Epidermal growth factor receptor and c-erbB-2 expression in normal breast tissue during the menstrual cycle.

EGF receptor (EGF-R) and c-erbB-2 are homologous tyrosine kinase transmembrane receptors. They are involved in controlling proliferation, and probably differentiation, of normal breast epithelial cells, and their expression has been linked to the prognosis of breast cancer. Their physiological roles in normal breast tissue remain to be elucidated, as most studies to date have involved breast cancer cell lines. We studied the location of EGF-R and c-erbB-2 in 100 samples of normal breast with standard immunohistochemical methods and double-labelling techniques. EGF-R was mainly expressed on the stroma and myoepithelial cells, whereas c-erbB-2 expression was exclusively epithelial. An image analyser was used to quantitate variations in their expression during the menstrual cycle. EGF-R and c-erbB-2 expression on epithelial cells was stronger during the luteal phase than the follicular phase (p < 0.01 for EGF-R). The pattern of expression was also compared with that in 28 breast cancers and 7 fibroadenomas.

Breast↗

Autologous tissue cardiac valve for aortic valve replacement: technical aspects and early results.

BACKGROUND: The known complications of heterograft bioprostheses and homograft valves have renewed the interest in the use of autologous material. A new technique to construct a tissue prosthesis for aortic valve replacement using the patient's pericardium harvested at the time of operation was developed. The glutaraldehyde-tanned pericardium is mounted on a stent requiring no suturing. Intraoperative testing assures adequate valve function. METHODS: The autologous tissue cardiac valve was implanted in 50 patients in the aortic position between March 1994 and May 1995. Echocardiograms were performed in all patients before hospital discharge, at 3 months (41 patients), and at the end of first postoperative year (12 patients). The mean age was 69.8 +/- 5 years (range, 58 to 82 years). Eighty-four percent of patients presented with aortic stenosis and 16% had a combined lesion. Additional cardiac procedures were performed in 21 patients. RESULTS: Aortic cross-clamp time was 72 +/- 19 minutes, and bypass time was 97 +/- 28 minutes. There were three in-hospital deaths, and 2 patients died within the first postoperative year. Predischarge echocardiography demonstrated excellent hemodynamics, with a mean gradient of 20 +/- 8 mm Hg and no or trivial aortic insufficiency in 45 patients. One patient had moderate aortic insufficiency. At first follow-up 36 patients (90%) were in New York Heart Association class I and 4 patients were in class II. Echocardiography showed no evidence of valve failure or degeneration (mean gradient, 17 +/- 5mm Hg; aortic insufficiency = grade 0 [trivial] in 35 patients, grade II in 3 patients, and grade III in 1 patient). Similarly, no degeneration or valve failure with increasing aortic insufficiency was seen in the patients studied at the end of the first postoperative year. CONCLUSIONS: These results demonstrate that an autologous tissue cardiac valve can be manufactured in the operating room without significant additional operating time. Intraoperative testing minimizes the risk of primary failure with aortic insufficiency. Short-term results are encouraging with good hemodynamic performance of the valve and no signs of degeneration. However, long-term durability needs to be demonstrated.

Aged↗

Genotypes of the vitamin-D-receptor gene and bone mineral density in Caucasoid postmenopausal females.

OBJECTIVE: To evaluate the relation of bone mineral density (BMD) to inherited polymorphisms within the gene coding for the vitamin D receptor (VDR) in postmenopausal women. METHODS: DNA samples from 163 post-menopausal women and from 112 controls were genotyped for common allelic determinants within the VDR gene as defined by the restriction enzyme sites for BsmI, ApaI, and TaqI. BMD was evaluated at the lumbar spine (L2-L4) by dual energy X-ray absorptiometry. Single restriction enzyme site polymorphisms as well as their joint genotypes were evaluated for their association with BMD in postmenopausal women. RESULTS: The three restriction site polymorphisms showed a close association indicating linkage disequilibrium (P < 0.0001). There was no relationship between any of the single restriction site polymorphisms and BMD. The distribution of the five most common joint genotypes among postmenopausal women and controls was similar. There was no relation of BMD and any of the five most common VDR genotype groups. Females more than 5 years after menopause had a significantly lower BMD than those less than 5 years after menopause (P < 0.001). This age-related decrease of BMD was also decernible within genotype groups. CONCLUSION: In our population, the postmenopausal period has a major influence on BMD, but BMD is not controlled significantly by any of the common allelic variations within the VDR gene.

Absorptiometry, Photon↗

Perioperative myocardial injury with different modes of antegrade and retrograde cardioplegic delivery.

The effect of three cardioplegic protocols on perioperative myocardial injury was studied in 62 coronary artery bypass grafting (CABG) patients randomized into three groups with either antegrade or retrograde cold blood cardioplegia, or coronary sinus occlusion during antegrade supply. During the aortic cross-clamp time anterior and posterior septal temperatures were recorded, indicating the distribution of cardioplegic solution within the myocardium. Serum creatine kinase (CK), CK-isoenzyme MB and myoglobin as well as 12-lead electrocardiograms (ECG) were analyzed. Statistical analysis showed no effect of the cardioplegic protocol, whereas the patient's preoperative status, aortic cross-clamp time and intraoperative myocardial temperature had significant (P < 0.05) effects on immediate postoperative CK and CK-MB enzyme release. Creatine kinase-MB peak values were significantly increased in patients with major vessel disease and reduced left ventricular function (92 +/- 53 U/l versus 67 +/- 25 U/l). Both CK and CK-MB values were significantly higher in patients with aortic cross-clamp times of more than 1 h than in patients with shorter clamping times (661 +/- 188 and 78 +/- 40 U/l versus 500 +/- 200 and 57 +/- 24 U/l). Patients with 22 +/- 3 degrees C myocardial temperature before terminal cardioplegia had significantly elevated CK as compared to patients with temperatures of 15 +/- 2 degrees C (665 +/- 185 U/l versus 510 +/- 211 U/l). However, enzyme peak values had only poor predictive power for postoperative ECG changes, suggesting that enzyme peaks were not necessarily a sign of perioperative ischemia. Patients with major vessel disease and reduced myocardial function, with aortic cross-clamp time of more than 1 h and/or inadequate intraoperative myocardial cooling may be highly susceptible to global ischemia and operative procedures, and therefore show elevated peak enzyme levels shortly after surgery. In contrast, elevated myoglobin peaks within 1 h after aortic declamping were significantly correlated to perioperative signs of transient ischemia (P < 0.02).

Aged↗

Analysis of stimulant locomotor effects of modafinil in various strains of mice and rats.

Locomotor effects of modafinil were analysed and compared in various strains of mice and rats. A stimulation of locomotor activity was evidenced in all tested strains of mice: Swiss CD1, BALB/c, DBA2, C3H, B6CBAF1/JICO, Nude CD1 and in all tested strains of rats: Long Evans, Sprague Dawley, Wistar. In mice, from 10 mg/kg intraperitoneal, a precocious stimulant effect was observed. The drug seems to operate in its native form on the mouse brain since its intracerebroventricular administration (from 15 micrograms/mouse) elicited a stimulation of locomotion. In rats, the effective doses were higher (from 40 mg/kg ip); the effects of modafinil mainly oppose to the decrease in locomotion (habituation) which normally occurs in control animals. In addition, it was observed that administration of modafinil in rats habituated to their environment induced a recovery of locomotor activity.

Analysis of Variance↗

Loss of heterozygosity of the RB gene is a poor prognostic factor in patients with osteosarcoma.

PURPOSE: The usual therapy of osteosarcoma is neoadjuvant chemotherapy, followed by surgery, then by postoperative chemotherapy. There is no prognostic factor to predict, at diagnosis, the histologic response and final outcome. Inactivation of the retinoblastoma-susceptibility gene RB is associated with the pathogenesis of several human cancers. In primary osteosarcomas, loss of heterozygosity (LOH) at the RB locus has been found in greater than 60% of cases. The aim of this study was to determine the potential early prognostic value of LOH of RB gene on the biopsy material at diagnosis. PATIENTS AND METHODS: Forty-seven patients with primary osteosarcoma, treated in four French institutions, were studied. LOH was studied by polymerase chain reaction (PCR) of an informative RB DNA polymorphism. RESULTS: Assessment of LOH at the RB gene could be completed on 34 heterozygous patients only. LOH was found in 24 cases (70%). The event-free survival (EFS) rate at 60 months is 100% for patients without LOH, 43% for all patients with RB LOH, and 65% for nonmetastatic patients with RB LOH. The difference in EFS is highly significant at P = .008 and P = .024, respectively. Histologic response after preoperative chemotherapy did not show significant correlation with LOH status. CONCLUSION: RB gene LOH appears to be an early predictive feature for osteosarcomas that indicates a potential unfavorable outcome. RB LOH study might shortly help to identify high-risk patients earlier. If this is verified, therapy could then be adapted earlier to the individual's real risk of relapse.

Adolescent↗

Operative management of aortic arch aneurysm using profound hypothermia and circulatory arrest.

Since the first successful replacement of the aortic arch with perfusion of the head, various methods have been employed to preserve cerebral function during aneurysm operations. Although deep hypothermia was used for surgery of the aortic arch, as early as 1963, the introduction of prolonged circulatory arrest has simplified replacements of the aortic arch. Between October 1990 and September 1993, 69 patients underwent aortic arch replacement for aneurysmal disease at the Dept. of Cardio-Thoracic Surg., University of Vienna. 52 patients had an acute dissection Type A, 17 patients were operated on electively. The patients age (48 male, 21 female) ranged between 16 and 81 years. Primary diagnosis was hypertension (n=44), marfan (n=14), unknown (n=10) and trauma (n=1). Total cardiopulmonary bypass was established via femoral artery cannulation. All patients received Cortison and Thiopental for added cerebral protection. Deep hypothermia (12 degrees C), confirmed by 0-EEG, and circulatory arrest were induced in all patients. The aneurysm was opened longitudinally and a full thickness single patch or "island" of aortic wall, containing the origins of the three arch vessels, was constructed and anastomosed in a continuous fashion to an albumin coated graft. 68 patients survived the operation (intraoperative mortality 1%). The 30-day mortality was 23% (n=16). Twelve patients died of multiorgan failure, two patients of a stroke and two due to myocardial infarction. The mean cerebral circulatory arrest time was 32 minutes (range 11-61 min.). Our experience with aortic arch replacements using profound hypothermia and circulatory arrest supports our contention, that it is the method of choice in this very difficult surgical field.

Adolescent↗

Hybridization of 2,659 Clostridium perfringens isolates with gene probes for seven toxins (alpha, beta, epsilon, iota, theta, mu, and enterotoxin) and for sialidase.

OBJECTIVE: To genetically characterize Clostridium perfringens isolates for association of pathologic type with various diseases. DESIGN: Prospective study. SAMPLE POPULATION: 2,659 C perfringens isolates from various nonhuman animals species, human beings, and foods. PROCEDURE: Colony hybridization with DNA probes for 7 toxin (alpha, beta, epsilon, iota (subunits a and b), theta, mu, and enterotoxin) genes and 1 sialidase gene were performed to group the isolates by pathologic type. RESULTS: Enterotoxin-negative type-A isolates were the most common (2,575/2,659), were isolated from all sources, and were separated into 5 pathologic types. In cattle and horses with enterotoxemia, essentially only these pathologic types were identified. The enterotoxin-negative isolates of types C or D each had a single pathologic type. Type-C isolates were isolated only from swine with necrotic enteritis and type-D isolates from small ruminants with enterotoxemia, except that 1 type-D isolate was also found from a healthy fish. Type-B or -E isolates were not found. Among the 47 enterotoxin-positive isolates, 5 isolates from sheep or deer were type D and the other 42 were type A. These 42 isolates were grouped into 3 pathologic types: 1 type was isolated from samples of almost all origins, but the other 2 types were found in only 5 fish, 4 human beings, and 1 dog. CONCLUSIONS AND CLINICAL RELEVANCE: Genetic characterization of these isolates allowed identification of 11 different pathologic types. This approach may be useful in molecular diagnosis and prophylaxis of clostridial disease.

Animals↗

[Clinical experience with a novel surgical technique: laparoscopy-assisted vaginal hysterectomy].

A new surgical technique, the laparoscopically assisted vaginal hysterectomy (LAVH) is evaluated through the clinical course of a group of patients operated for hysterectomy in the years 1993-1995. Although the groups of patients being operated for LAVH, vaginal or abdominal hysterectomy have not been randomized, we conclude that the laparoscopic assistance allows the vaginal approach of hysterectomies that should have been otherwise operated by laparotomy. Medical and financial advantages of this technique are discussed.

Adult↗

[High grade osteosarcoma of the lower limb. Complications and results of the treatment of 20 patients].

UNLABELLED: Over 11 years we treated 30 osteosarcomas: 20 of them were high grade non metastatic osteosarcomas of the lower limb, which were treated by neoadjuvant chemotherapy (Rosen T10, or OS 87 protocol of the French Society for Pediatric Oncology). MATERIAL AND METHODS: There were 12 males and 8 females; the mean age was 19 years (range 12-51). The site of the tumor was the femoral neck (1 case), femoral diaphysis (2 cases), distal femur (12 cases), proximal tibia (4 cases), distal tibia (1 case), 3 were IIA and 17 IIB according to Enneking system. Conservative treatment was performed in 17 cases: there were 12 knee prostheses, 4 allografts and 1 knee arthrodesis with allograft. RESULTS: a) Surgical complications: Mechanical complications occurred in 10 patients. The function was preserved 8 times. In 2 patients the knee became stiff. An infection occurred in 3 patients: a conservative treatment was possible in 2 of them with a fair result. In the third case, an above-the-knee amputation had to be done. b) Functional results were studied according to Enneking rating. 14 arthroplasties (12 done as first surgical treatment and 2 after mechanical complication) had a 68, 19 score. c) Oncologic results: 8 patients were good respondents and 12 patients were bad respondents to chemotherapy according to Huvos grading. One local relapse was observed which could be treated by mean of a second chemotherapy and a prosthetic reconstruction. The patient is still alive and disease-free at 7 years (9 years after the diagnosis of the osteosarcoma). 5 patients had distant metastasis (lung, bones, and brain). One out of 5 was good respondent and 4 out of 5 are presently dead. Using Kaplan Meier statistical analysis, the overall survival wzs 76.8 per cent and the event-free survival was 67.4 per cent at 80 months. CONCLUSION: We preferred a simple prosthetic reconstruction without osseous sleeve or an intercalary allograft if possible: these procedures allow the patient very rapid autonomy to have despite a prolonged chemotherapy.

Actuarial Analysis↗