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Biomedical subjects

P Vincent

Publications and source records attributed to P Vincent.

At least 19 recordsLinked to original sources

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

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

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

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

[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

[Stage III non-small cell lung cancers: prospects of concomitant radiochemotherapy].

The prognosis of stage III non small cell lung cancer is reportedly poor, particularly in patients with mediastinal lymph node involvement. These patients may be either good surgical candidates, marginally resectable, or inoperable for technical or medical reasons, but, in any case, surgery and/or radiotherapy are curative in only a minority of them. The high incidence of early distant failures underscores the need for early and effective systemic therapy in association with local treatment, since occult metastatic disease is present in most patients at the time of diagnosis. Recent phase III trials have demonstrated significant benefit to induction chemotherapy prior to irradiation or surgery in reducing the distant metastasis rate. However, poor local control remains a major issue in these locally advanced tumors. In patients with inoperable disease, the concomitant use of chemotherapy along with radiotherapy substantially improves local control. For operable patients, induction chemotherapy with concomitant moderate-dose radiotherapy improves local control as well, and may facilitate surgical resection in marginally operable cases. Currently, a number of phase II clinical trials report encouraging results with concomitant chemoradiotherapy used either prior to surgery or with curative intent in locally advanced non small cell lung cancer.

Antineoplastic Agents

Bedrest compliance for women with pregnancy problems.

Bedrest has long been recommended for high-risk pregnancies, but recent studies question its effectiveness in improving pregnancy outcomes. To be effective, the women for whom bedrest is recommended must practice it. This study examined degree of compliance and reason for noncompliance in women for whom bedrest was recommended, and outcomes of pregnancy among high-risk women who complied compared with those who did not. The subjects were 326 high-risk pregnant women who were prescribed bedrest for preterm labor, blood pressure problems, or bleeding problems. Of that group, one-third did not comply with the bedrest recommendation. These women had more children, were not currently married, had more stress, did not attend prenatal classes, continued drinking alcohol during pregnancy, and were not trying to get pregnant compared with women who complied. Reasons for noncompliance included the need to care for children, not feeling sick, household demands, lack of partner or family support, need to work, and discomfort. The pregnancy outcomes for the women who complied were similar to those of the women who did not comply. These findings support the importance of more research on the practice of prescribing bedrest to improve pregnancy outcomes.

Bed Rest

Radiation therapy with concomitant continuous infusion cisplatin for unresectable nonsmall cell lung carcinoma.

PURPOSE: This pilot study was designed to test the tolerance and effectiveness of concurrent continuous infusion cisplatin and radiotherapy in the treatment of unresectable nonsmall cell lung (NSCL) cancer. METHODS AND MATERIALS: Between July 1989 and July 1991, 92 consecutive patients with either medically or technically inoperable NSCL cancer were treated with thoracic radiotherapy and concomitant chemotherapy. Radiotherapy consisted of a total dose of 70 Gy delivered in 2 Gy daily fractions over 9 weeks with a planned 2-week break after 40 Gy. During the second week of each cycle of radiotherapy, cisplatin was administered, 20 mg/m2/day for 5 days as a continuous infusion. Eighty-five patients were evaluable. RESULTS: Overall response rate was 81.7% (65.9% complete response). Medically operable patients were considered for curative surgical resection following 40 Gy and one cycle of chemotherapy; 11 patients underwent resection with 3/11 having no pathologic evidence of tumor. Median survival for all 85 patients was 11.4 months with a median follow-up of 27 months. Overall survival was 48.2%, 27.5%, and 25% at 12, 24, and 36 months, respectively. Survival was independent of tumor stage, histology and grade, and patient age and gender. Patients having a complete response (n = 54) had a 2-year survival of 42.1% compared to 3.2% for partial-responders and nonresponders (n = 31; p < 0.0001). Patients undergoing surgical resection (n = 11) had a 2-year survival of 75.8% compared to 20.6% for those treated with chemoradiotherapy alone (n = 74). Forty-eight patients have died of their disease. There were two treatment-related deaths, seven deaths of intercurrent disease and three of unknown causes. Eighteen of 25 patients alive at the time of analysis were without evidence of disease. Actuarial local control was 50.6% at 1 year, and 33.3% at 2 years. The distant failure rate was 47.8% at 2 years. Major acute toxicities, mainly hematologic or gastrointestinal, occurred in less than 10% of patients. Esophagitis was mild and infrequent (8.4%). Severe late pulmonary fibrosis occurred in 5.2% of patients and resulted in two treatment-related deaths. CONCLUSION: Concomitant chemoradiotherapy was well tolerated, resulted in a high rate of local control, and in a survival benefit for patients demonstrating a complete response or going on to surgical resection. The incidence of distant metastases continues to be high and future strategies should be directed at improving systemic therapy.

Adult

Trends in bacterial infections in febrile neutropenic patients: 1986-1992.

BACKGROUND: Bacterial infection is a major cause of morbidity and mortality in neutropenic patients. AIMS: (1) To review patterns and trends in bacterial infections in three cohorts of febrile neutropenic patients managed by a single unit over a seven year period. (2) To relate any changes to the use of central venous (Hickman's) catheters and high-dose cytosine arabinoside chemotherapy. METHODS: Retrospective review of the results of initial bacteriological work-up performed on 344 episodes of febrile neutropenia. The three cohorts were 1986-87 (n = 102), 1989-90 (n = 92) and 1991-92 (n = 150). RESULTS: (1) The ratio of gram-negative to gram-positive bacteraemias fell from 1.36 in the first cohort to 1.05 in the second and 0.40 in the third (p = 0.03). There was a fall in both percentage and number of gram-negative isolates coupled with a rise in the frequency of gram-positive isolates. (2) Coincidentally there was a rise in the frequency of positive cultures from Hickman catheter entry wounds and an increasing frequency of simultaneous isolation of the same organism from the catheter entry site and the blood. The types of organisms isolated from catheter entry wounds showed a trend towards fewer gram-negative and more gram-positive. (3) A relationship was observed between the use of high-dose cytosine arabinoside chemotherapy and the incidence of bacteraemia (p = 0.025) but not with the change in types of organisms. CONCLUSIONS: Over seven years we have documented a major change in the types of infections, particularly bacteraemias, seen in febrile neutropenic patients. In our institution the more widespread use of intravenous catheters and high-dose cytosine arabinoside chemotherapy have been identified as two possible contributing factors.

Bacteremia

High prevalence of Helicobacter pylori infection in cohabiting children. Epidemiology of a cluster, with special emphasis on molecular typing.

Intrafamilial cases of infection with the same strain of Helicobacter pylori (H pylori) have been reported but these clusters were too small to distinguish between person to person spread or coinfection from a common environmental source. To gain more information on the mode of transmission of H pylori, an epidemiological survey with bacterial strain differentiation by restriction endonuclease analysis of chromosomal DNA was carried out in an institution of 117 children with encephalopathy (aged 3.5 to 19 years). All children with antibodies against H pylori had gastroscopy to obtain gastric biopsy specimens. The prevalence of infection (confirmed histologically or microbiologically, or both) was 38% (45/117), and rose to 67% in one of the five sections of the institution. H pylori was isolated in 34/45 cases, and 22 different strains were found of which five strains were present in more than one child. Up to seven children were infected by the same strain, five of them were living in the same section. Analysis of the characteristics of infected children showed the predominant role of living conditions and the period of time cohabiting in this unexpectedly high prevalence of H pylori infection in children living in good sanitary conditions.

Adolescent

A randomised dosage study of ceftazidime with single daily tobramycin for the empirical management of febrile neutropenia in patients with hematological diseases.

A single-institution, randomised trial was conducted to compare the clinical and microbiological efficacy of two different doses of ceftazidime in combination with a single daily dose of tobramycin for the empirical management of febrile neutropenic patients with hematologic disorders (absolute neutrophil count < 1 x 10(9)/l). Upon the development of fever or signs of sepsis, patients received either 2 g ceftazidime every 8 h plus a single daily dose tobramycin (5 mg/kg/day) (C2T, n = 73) or 1 g ceftazidime every 8 h plus a single daily dose of tobramycin (C1T, n = 77). In addition, flucloxacillin (1-2 g every 4 h) could be added if there was clinical suspicion of staphylococcal infection. Analysis was performed for the whole group and for the subset which did not receive flucloxacillin. When evaluated at 96 h, 70% (95% CI, +/- 11%) of patients randomised to C2T and 60% (95% CI, +/- 11%) randomised to C1T had responded (chi 2 = 1.27, P = 0.26). The response rates at 96 h for those who did not receive flucloxacillin were 77% (+/- 12%) and 74% (+/- 13%), respectively (chi 2 = 0.01, P = 0.92). Overall, 68 (93% +/- 6%) and 72 (94% +/- 6%) patients, respectively, eventually became afebrile (chi 2 = 0.06, P = 0.81). Renal function, as judged by serum creatinine, was unaffected by either antibiotic schedule. Within 10 days of antibiotic commencement there was one death in each arm and overall there were five deaths in each arm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

A comparison of the binding of biotin and biotinylated macromolecular ligands to an anti-biotin monoclonal antibody and to streptavidin.

A competitive enzyme immunoassay was used to study the binding of biotinylated macromolecular ligands and d-biotin to an anti-biotin monoclonal antibody and to streptavidin. Solid phase BSA-c-biotin competed with biotin or biotinylated macromolecular ligands in solution for receptor binding. The concentration of d-biotin required to inhibit streptavidin binding to solid phase BSA-c-biotin by 50% was 11.5 pM. This streptavidin-biotin interaction was taken as having an affinity/avidity index of 100 and all other receptor-ligand interactions were calculated relative to this. The avidity indices calculated for streptavidin interactions with BSA-c-biotin and IgG-biotin were 17.6 and 6.6 respectively, whereas for anti-biotin the values for these ligands were 20.5 and 19.9 respectively. The interaction of anti-biotin with d-biotin had an affinity index of 0.001. Although streptavidin has the greatest binding affinity for d-biotin, its avidity for biotinylated ligands was considerably lower and comparable to that observed for anti-biotin-biotinylated macromolecule interactions.

Animals

Translocation (Y;1)(q12;q21) in acute leukemia.

This report documents one patient with myelodysplasia evolving into acute leukemia who showed a t(Y;1) translocation confirmed by in situ hybridization. Most of the q arm of the Y chromosome was translocated to an additional q arm of chromosome 1, resulting in trisomy 1q. To our knowledge only four other cases with this t(Y;1) have been reported.

Adult

Idazoxan decreases estrogen-induced lordosis in female but not "hormone-independent" lordosis in male guinea pigs of an inbred strain.

This experiment examined whether the imidazoline idazoxan (which binds to alpha-noradrenergic receptors and to imidazoline-preferring sites) interferes with hormone-dependent or hormone-independent lordosis responses. Ovariectomized (ovx) Strain 2 female guinea pigs which were sexually receptive after receiving estradiol benzoate (EB; 3 micrograms/d for 3 days) were injected with either idazoxan (10 mg/kg) or with vehicle at 24 hr after the last EB injection. Idazoxan significantly decreased EB-facilitated lordosis responses in these females. Castrated Strain 2 males, which show lordosis behavior without gonadal hormone administration, were injected with the same dosage of idazoxan (10 mg/kg) or with vehicle. Idazoxan did not inhibit lordosis behavior in these males.

Adrenergic alpha-Antagonists

Neighboring cerebellar Purkinje cells communicate via retrograde inhibition of common presynaptic interneurons.

Paired tight-seal whole-cell recordings were obtained from neighboring Purkinje cells in cerebellar slices. Under voltage clamp, spontaneous inhibitory postsynaptic currents resulted from the activity of GABAergic interneurons, stellate and basket cells. Up to 80% of inhibitory postsynaptic currents in paired recordings were in register. This correlation was not affected by antagonists of glutamate receptors, faded with distance, and was abolished by tetrodotoxin. Earlier work showed that voltage-gated Ca2+ entry into a Purkinje cell elicits a transient presynaptic inhibition of inhibitory postsynaptic currents. It is now shown that this inhibition is not restricted to the stimulated cell, but that it is transmitted to its neighbors. The results indicate that Purkinje cells exchange information by an unconventional mechanism involving retrograde control of inhibitory synapses.

Animals

[Treatment of obstructive bronchial cancers with high dose, endobronchial curietherapy. Technical aspects and clinical results].

Between September 1990 and September 1991, 35 patients with mainly recurrent or residual endobronchial carcinoma were treated with 91 high-dose-rate endobronchial brachytherapy applications. Treatment technique was fairly simple and could easily be performed on an outpatient basis. Endoscopic placement of one or two applicators is followed by computerized dosimetry and irradiation during a median time of 10 minutes. Treatment included 3 sessions of 10 grays measured at 10 mm from the center of the radioactive source at 2-week intervals. Response rate was 81.8% including 51.5% complete clinical response. There were 12 microscopically complete response out of 14 patients biopsied. Immediate tolerance was excellent in 90% of cases. However, late complications were severe in 25% of cases. Ongoing radiobiological research should determine an optimal therapeutic approach in term of efficacy and long term toxicity before using endobronchial brachytherapy as a part of the initial management of unresectable lung cancers.

Adult

Single daily ceftriaxone and tobramycin in the empirical management of febrile neutropenic patients: a randomised trial.

A single-institution, randomised pilot trial was conducted to compare the clinical efficacy, microbiological efficacy and possible toxicity of empirical single daily antibiotic administration in febrile neutropenic patients with haematologic disorders (absolute neutrophil count < 1 x 10(9)/l). Upon the development of signs of sepsis, patients received either single daily dose tobramycin (5 mg/kg per day) plus ceftriaxone (2 g/day) (C + T, n = 47) or tobramycin (1.5 mg/kg, every 8 h) plus azlocillin (4 g, every 6 h) (A + T, n = 45). In addition, flucloxacillin (1-2 g, every 4 h) could be added if there was clinical suspicion of staphylococcal infection (17 in each arm). Analysis was performed for the whole group and for the subset which did not receive flucloxacillin. When evaluated at 96 h, 62% of patients randomised to C + T and 67% randomised to A + T had responded (95% confidence interval (CI) for the difference in rates, -25% to +15%). Ninety-six hour response rates for those who did not receive flucloxacillin were 73% and 78%, respectively (95% CI, -17% to +27%). Overall, 42 (89%) and 41 (91%) patients, respectively, eventually became afebrile (95% CI, -14 to 10%) and there was no evidence of altered renal function or electrolyte imbalance in patients randomised to single daily antibiotic therapy compared with the conventional (multi-daily dose) arm. Within 10 days of antibiotic commencement there was 1 death in the C + T arm and 4 deaths in the A + T arm, although overall there were 4 deaths in each arm. Our results suggest that single daily empirical antibiotic therapy with tobramycin and ceftriaxone is efficacious and is not associated with an increased incidence of renal dysfunction or electrolyte imbalance compared with conventional administration schedules of azlocillin plus tobramycin. Single daily therapy has the potential to lead to savings in nursing-staff time and materials and may well contribute to an improved quality of life for febrile neutropenic patients.

Adolescent