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Biomedical subjects

P Vincent

Publications and source records attributed to P Vincent.

At least 73 records · Page 4Linked to original sources
PubMed1996

Spatio-temporal dynamics of cyclic AMP signals in an intact neural circuitm.

The functional properties of neuronal networks can be reconfigured by a variety of modulatory neurotransmitters, which may alter the excitable properties of neurons or the strengths of synaptic connections. Many of these neuromodulators act via the intracellular second messenger cyclic AMP, but their effects on the spatial distribution of cAMP concentration have never been examined in an intact neural circuit. We therefore used the cAMP-indicator dye FICRhR (refs 1, 2) to investigate the effect of several neuromodulators (octopamine, dopamine, acetylcholine, serotonin and proctolin) on cAMP distribution in identified neurons of the lobster stomatogastric ganglion (STG). When added to the bath solution, each of these neuromodulators produced a unique pattern of cAMP transients among the different neurons of the STG. Electrical stimulation of neurons innervating the STG causes synaptic release of endogenous modulators, leading within a few seconds to local increases of cAMP in fine neurite branches, the site where many modulators are thought to act. After prolonged stimulation, cAMP diffuses from the site of production to throughout the neuritic tree and eventually to the cell body. Diffusion of cAMP may explain how transient localized inputs to a neuron can produce long-range effects such as long-term changes in gene expression.

Animals↗
PubMed1996

Fluctuations of inhibitory postsynaptic currents in Purkinje cells from rat cerebellar slices.

1. Paired patch-clamp recordings were performed in cerebellar slices to study IPSCs evoked by interneurones (stellate and basket cells) in Purkinje cells. 2. IPSCs were first examined while keeping the presynaptic cell in the cell-attached mode. In some of these experiments IPSCs had a remarkably broad amplitude distribution. Large variabilities were associated with large mean IPSC amplitudes and were preferentially obtained with presynaptic basket cells. Action currents recorded from the presynaptic interneurone in the cell-attached mode were reproducible indicating that the variability occurs downstream of action potential generation. 3. The variability of IPSC amplitudes was observed independently of the instantaneous firing rate of the presynaptic cell, and could therefore not be ascribed to synaptic fatigue. 4. Highly variable IPSC amplitude were also obtained if the presynaptic interneurone was placed in whole-cell recording with a potassium-based intracellular solution. 5. If the recording pipette were filled with Cs+ ions a large increase in the mean of the IPSCs was observed within seconds after establishing the whole-cell recording. In Cs(+)-dialysed cells it was possible to modulate the mean IPSC amplitudes by altering the characteristics of the presynaptic stimulation. IPSC amplitudes obtained in response to presynaptic voltage pulses to 0 mV were large and had little scatter. IPSCs obtained in response to pulses near +60 mV, close to the reversal potential of presynaptic Ca2+ currents, had a much lower mean amplitude and also had little scatter. Thus presynaptic application of Cs+ ions both increases the mean amplitude and decreases the variability of the postsynaptic response. 6. To test whether interneurones could be coupled by electrical synapses, paired recordings were performed from neighbouring interneurones. No correlation was found between the firing patterns of such paired recordings, indicating that electrical coupling among presynaptic neurones is not responsible for large IPSC fluctuations as recorded in Purkinje cells. 7. Finally, IPSC fluctuations were investigated in paired recordings from two Purkinje cells. IPSCs corresponding to the activity of common interneurones were identified on the basis of temporal correlation. By plotting the amplitudes of such common IPSCs in one cell against those obtained simultaneously in the other cell, the pattern of IPSCs due to a single presynaptic neurone could be identified. These results show that fluctuations of IPSCs due to the same interneurone in one postsynaptic Purkinje cell are independent of those occurring in another Purkinje cell. 8. The results indicate that the major source of fluctuations is localized within the axonal arborization of presynaptic interneurones. The results with presynaptic Cs+ require that the fluctuations involve the concerted release of several presynaptic vesicles. Two possible mechanisms for such multiquantal events are discussed: fluctuations in presynaptic depolarization, and fluctuations in a regenerative Ca2+ amplification mechanism.

Animals↗
PubMed1996

Concurrent cisplatin, etoposide, and radiotherapy for unresectable stage III nonsmall cell lung cancer: a phase II study.

PURPOSE: Prognosis of unresectable Stage III nonsmall cell lung cancer (NSCLC) treated with thoracic radiotherapy alone has been disappointing. In recent years, several Phase III trials have demonstrated encouraging results with induction chemotherapy, but with poor long-term local control. Concurrent cisplatin alone during the radiation therapy course has resulted in improved local control, but without efficacy on occult metastatic disease. Intensification of chemotherapy during radiation has the potential of improving both local control and metastasis-free survival. This Phase II study was undertaken to determine the feasibility, toxicity, response rate, local control, and survival of concurrent chemotherapy with cisplatin-etoposide and radiotherapy in unresectable Stage IIIA and IIIB nonsmall cell lung cancer. METHODS AND MATERIALS: Between February 1992 and April 1993, 50 patients with either medically or technically inoperable Stage III NSCLC were treated with concurrent chemoradiotherapy. Thoracic radiotherapy was administered to a total dose of 60 Gy. Concurrent chemotherapy consisted of cisplatin 20 mg/m2/day plus etoposide 50 mg/m2/day, from day 1 through day 5, every 4 weeks for four cycles. Medically operable patients were evaluated for surgical resection after 45 Gy and two cycles of concurrent chemotherapy. All patients received an esophagitis preventive regimen. RESULTS: Response rate was 84%, including 68% complete response. With a minimum follow-up of 23 months, overall survival was 70% at 1 year, 39.7% at 2 years, and 34.7% at 3 years. Median survival was 18 months. Age, performance status, histologic type and grade, and stage and tumor size, did not influence survival, with the exception of contralateral nodal involvement (p = 0.0055). Patients achieving a complete response (n = 34) had a 2-year survival of 58.4% compared to 0% for nonresponders (p < 0.0001). Patients who could benefit from surgery (n = 9) had a 2-year survival of 77.8% compared to 31.2% for nonoperated patients (p < 0.013). Seventeen patients (34%) are currently alive and free of disease. Actuarial local control was 63.4% at 1 year, and 58.5% at 2 and 3 years, respectively. Major hematologic toxicity occurred in 24% of the patients. CONCLUSIONS: Concomitant chemoradiotherapy with cisplatin and etoposide at this dose level is a well tolerated outpatient regimen, which resulted in a high local control rate, and an encouraging survival at 1, 2, and 3 years. A direct comparison of this treatment schedule to induction chemotherapy followed by radiotherapy, or concurrent chemoradiation therapy using cisplatin alone, appears warranted.

Adult↗
PubMed1996

The influence of genotype and environment on the physiological and metabolic diversity of Fusarium compactum.

Fungal species produce a large variety of secondary metabolites which are of considerable interest to the pharmaceutical industry. It is clear that the secondary metabolite production of a species varies significantly in strains from different geographic locations and from different habitats. The influence of genotype and environment on metabolite production is, however, poorly understood. In this study we examined the influence of genotypic variability, physiological variability, environmental location, and habitat on metabolite production by Fusarium compactum. Isolates of the fungus from two geographic locations and two distinct habitat types were examined for growth on 95 different carbon sources, and genotypic variability was determined using RAPDs and rDNA-RFLP analysis. In a blind test secondary metabolite production was assessed using HPLC profiles of methanolic cell extracts. A number of correlations were observed between genotypic groupings, as determined using parsimony, and specific metabolic production. Similar correlations were also observed with physiological groups although genotypic analysis proved to be a more sensitive predictor of metabolite variability. The data suggest a complex relationship between environment, genotype, and metabolite production but highlight the use of genetic screening as a means of optimizing the changes of identifying a wide range of metabolites from a given species.

Base Sequence↗
PubMed1996

[High-dose rate endobronchial brachytherapy: results and complications in 189 patients].

Between September 1990 and March 1995, 189 patients were treated with high-dose-rate endobronchial brachytherapy. Most patients (70%) presented with either recurrent or persistent symptomatic endobronchial tumor after standard therapy. A minority of the patients (12%) had small endobronchial tumor and were unfit for surgical resection or radiotherapy. Treatment was delivered weekly and consisted of three to four 8- to 10-Gy radiotherapy fractions applied at 10 mm from the source. Major symptomatic improvement was obtained on hemoptysis (74%), dyspnea (54%), and cough (54%). Complete endoscopic response occurred in 54.5% of the cases. Median survival was 7 months for the entire group. For small strictly endobronchial tumors, complete response rate was 95.5%, median survival was 17 months, and 30-month survival was 46%, with a plateau starting at 18 months. The rate of late grade 3 to 4 toxicity was 17%, including hemoptysis (n = 13), stenosis (n = 12), local necrosis (n = 8), and bronchial fistula (n = 3). By univariate analysis, no factor was found to be predictive of late toxicity. Our study confirms the benefit of endobronchial brachytherapy in the palliative treatment of endobronchial recurrences and in the curative intent treatment of small endobronchial tumors in patients not suitable for other forms of therapy.

Adult↗
PubMed1996

Attention disturbance in clinical depression. Deficient distractor inhibition or processing resource deficit?

Cognitive impairments in depression have recently been proposed as secondary to more basic attentional disturbances. Studies have shown that performance on the Stroop Color-Word Test is impaired in depressives, but it is not clear whether this impairment reflects a primary distractor inhibition disturbance or a more global cognitive dysfunction, such as a reduction of processing resources. In the present study, unmedicated clinical depressives were evaluated using a computerized Stroop Color-Word Test and the Visuo-Spatial Interference Test, a selective attention task that makes fewer demands on resources. Compared with normal subjects, depressives presented increased choice reaction times (CRT) and interference in both tests. Correlations were found between CRT and interferences only in depressives, favoring the processing resource hypothesis. Further exploratory analysis comparing the more rapid depressives and the slower normal subjects on CRT revealed that although these subgroups had comparable CRT, rapid depressives still exhibited increased interference on the Visuo-Spatial Interference Test. Thus, in non- or mildly retarded patients, a specific distractor inhibition deficit was observed in absence of resource deficit.

Adult↗
PubMed1996

[Preoperative radio-chemotherapy of stage III unresectable non-small cell lung cancer: results of a pilot study].

Prognosis of Stage III NSCLC remains dismal, particularly when mediastinal nodal involvement is present. In order to improve local control and to reduce early distant failures, we have treated Stage III patients with concurrent chemoradiotherapy since 1989. From September 1989 to February 1994, 140 patients were treated with concurrent chemoradiotherapy. Among these, 24 initially inoperable patients became operable after induction chemoradiotherapy. Characteristics: median age 51 years (35-70); squamous: 45.8%; non squamous: 41.7%; median tumor size: 8 cm; T3 (79.2%); T4a (12.5%); N2 (62.5%) and N3 (8.3%). Preoperative radiotherapy was delivered at a dose of 45 Gy (25 f) over 5 weeks to the mediastinum. Concurrent chemotherapy was continuous infusion cisplatin (n = 10) or cisplatin plus etoposide (n = 14). Five weeks later, radical surgery was carried out (lobectomy n = 14, pneumonectomy n = 10), followed by additional chemotherapy (n = 12) and/or radiotherapy (n = 6), according to histological response. Pathological CR rate was 29.2%. Grade III toxicities were digestive (12.5%), hematologic (8.3%) and infectious (4.2%). Three patients had severe non-lethal postoperative complications with one hemorrhage and two pneumothorax (12.5%). With a median follow-up of 41 months, overall survival at 2 and 5 years was 77.5%, and 72%, respectively. Actuarial local control at 5 years was 82.4%. Nine patients presented with distant metastases, including six with isolated brain metastases. This preoperative chemoradiotherapy regimen appears feasible without overwhelming toxicity and with an acceptable rate of postoperative complications. Despite a significant incidence of isolated brain metastases (25%), 5-year survival is highly encouraging since and appears substantially better than primary surgery.

Adult↗
PubMed1996

[Results of posterior lumbar intersomatic fusion in the treatment of isthmic spondylolisthesis. Apropos of 27 cases followed over more than 10 years].

PURPOSE OF THE STUDY: Posterior lumbar interbody fusion (PLIF) as described by Cloward, with laminectomy of the entire separate neural arch in spondylolisthesis, is a difficult operation. The purpose of this study is to evaluate the results of PLIF with autologous bony graft, without reduction or instrumentation in grade I and II spondylolisthesis. MATERIAL: The authors report the results of a series of 36 cases of spondylolisthesis (out of a series of 160 cases) operated on with PLIF, after a minimum of 10 years of follow-up (mean: 11.8 years, 10-16 years). 9 patients were lost for follow-up, 27 had been examined clinically and radiologically. 19 males and 8 females. Mean age 29.6 years (14 to 50). The series consisted in 24 lumbo-sacral disc and 3 L4-L5 disc fusion. Before operation, 25 patients suffered backache and 20 had sciatic. Mean preoperative listhesis according to Boxall was 29 per cent. METHODS: PLIF had been done with autologous bony graft and neural decompression without reduction. The thickness of the space had been restored with special progressive distractor. Postoperative back cast was used during 6 months. RESULTS: Postoperative nerve roots complications occurred in 4 cases and were regressive within 3 months. Results were excellent in 17 cases, good in 7 cases and poor in 3 cases. Patients returned to work after 9.8 months (13.6 months for heavy work). 26 patients had solid tomographic interbody fusions. No additional subluxation was noted. In 10 per cent of the cases the graft was partially crammed. In 7 cases a degenerative aspect of the upper disc was noted (symptomatic in 6 cases). The sagittal balance of the spine evaluated with a specific index showed persistent abnormality in 50 per cent of the cases but PLIF brought a significant improvement in 26 per cent. DISCUSSION: The rate of fusion is better than in series using bony allografts and better than in series using anterior interbody fusion. The analysis of the adjacent discs shows that it is not necessary to extend fusion to the upper disc. Instrumentation had not been used in this series but a cast seems to be indispensable. Instrumentation with plates and pedicular screws should be able to give more stability but is often responsible of iatrogenic lesions at the articular facets. CONCLUSION: This study confirms the good results obtained by PLIF with nerve roots decompression in spondylolisthesis. Fusion is stable and does not accelerate degenerative lesion of the upper disc.

Adolescent↗
PubMed1995

Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain.

Nicotine affects many aspects of behaviour including learning and memory through its interaction with neuronal nicotinic acetylcholine receptors (nAChR). Functional nAChRs are pentameric proteins containing at least one type of alpha-subunit and one type of beta-subunit. The involvement of a particular neuronal nicotinic subunit in pharmacology and behaviour was examined using gene targeting to mutate beta 2, the most widely expressed nAChR subunit in the central nervous system. We report here that high-affinity binding sites for nicotine are absent from the brains of mice homozygous for the beta 2-subunit mutation. Further, electrophysiological recording from brain slices reveals that thalamic neurons from these mice do not respond to nicotine application. Finally, behavioural tests demonstrate that nicotine no longer augments the performance of beta 2-1- mice on passive avoidance, a test of associative memory. Paradoxically, mutant mice are able to perform better than their non-mutant siblings on this task.

Animals↗
PubMed1995

Transmission and acquisition of Helicobacter pylori infection: evidences and hypothesis.

The role of Helicobacter pylori in gastroduodenal diseases has been established, but many ecological and epidemiological features remain unclear. Although H pylori infection is one of the most common infections in the world, the mode of transmission remains unknown. Uncommon extra-endoscopic isolation raises obstacles to a good understanding of epidemiological patterns, and no rational basis exists for a prophylaxis strategy. This work reviews the data on the reservoir of the bacteria and its ecological niche, the method of excretion from the site of infection and the possible circumstances of acquisition. Many features are completely unknown or still controversial, and interpretation is often speculative. At the present time, it can be assumed that the most likely mode of spread would be from saliva in childhood. However, further works are required to establish, whether or not, fecal transmission co-occurs in low hygiene conditions.

Animals↗
PubMed1995

A third locus for hereditary haemorrhagic telangiectasia maps to chromosome 12q.

Hereditary haemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is an autosomal dominant vascular disorder which associates epistaxis, mucocutaneous and visceral telangiectases, and recurrent haemorrhage with chronic anaemia and visceral shuntings. Recently, the tumour growth factor (TGF)-beta binding protein endoglin localized to 9q33-34 was identified as responsible for HHT in several large kindreds with pulmonary arteriovenous malformations (PAVMs). Additional linkage studies demonstrated that HHT is a genetically heterogeneous disorder with families unlinked to this region of 9q. In the families in which HHT was not linked to chromosome 9, less PAVMs were present. Furthermore, in one of these families, HHT was found linked to 3p22, where the TGF-beta II receptor is located. In this linkage study, we have analysed DNA from two families, in which HHT was unlinked to chromosome 9q and 3p, and PAVMs were absent, with a series of genetic markers on the centromeric region of chromosome 12. Using two-point linkage analysis, a significant lod score of Zmax = 7.86 at theta = 0.05 was obtained with the D12S85 microsatellite marker.

Antigens, CD↗
PubMed1995

Client characteristics associated with not keeping appointments for public health nursing home visits.

Home visits have been identified as an intervention strategy for high-risk pregnant women. A necessary component of this intervention strategy is for the women to be home for the visit with the nurse. The purpose of this study was to identify factors associated with women not keeping their home visit appointments with a public health nurse. Subjects were 232 low-income high-risk pregnant women who received at least one home visit by a public health nurse. Younger age, more stressful life events, receipt of medical assistance, inadequacy of prenatal care, noncompliance with health recommendations, and longer gestational time were associated with not keeping public health nursing appointments. While this study provides some insight into the factors associated with women not keeping their appointments with the public health nurse, further investigation is warranted to identify strategies to reduce the incidence of not-kept appointments.

Adult↗
PubMed1995

[Radiotherapy and concomitant cisplatin in stage III non-small cell bronchial cancer: results of a pilot study].

From July 1989 to July 1991, 73 previously untreated patients with histologically proven stage III inoperable non-small cell lung cancer have been treated with standard fractionation radiation therapy and concomitant cisplatin by continuous infusion. Thoracic irradiation was delivered at a dose of 40 grays in 20 fractions over 4 weeks to the entire mediastinum, ans was followed after a two-week rest by a boost of 30 grays in 15 fractions over 3 weeks with oblique fields sparing the spinal cord. Continuous infusion cisplatin was given during the second week or each radiation therapy sequence at a dose of 20 mg/sqm/24 hours during five days (120 hours) with usual hyperhydratation and antiemetic measures. Toxicity was essentially hematologic and gastro-intestinal but there was only 4.1% grade 3 or grade 4 complications. Radical surgery became feasible after the first cycle of treatment in 10 patients (13.7%). Complete response rate as determined by CT-scan and fiberoptic bronchoscopy was 61.6%. At a median follow-up of 26 months, actuarial overall survival at 1, 2 and 3 years was 46.6%, 27.7% and 24.5%, respectively. There were no local recurrence or distant relapses after 3 years, which will hopefully result in long-term survival in one quarter of these patients. These results compare favorably with other studies combining radiation therapy and concomitant cisplatin with different dosage and schedule. Local control appears substantially improved by this combined modality treatment over radiation therapy alone. However, the incidence of distant metastasis remains significant, especially during the first year of follow-up. Further improvement of early and long-term survival could possibly result from the incorporation in this protocol of a second drug active against subclinical dissemination.

Actuarial Analysis↗