Biomedical subjects
Publications and source records attributed to B Richard.
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Small-animal ultrasound imaging has been made possible using high-resolution imaging devices. The spatial resolution is therefore sufficient to accurately measure anatomical parameters in mice. This paper reviews some of the main applications of high-resolution ultrasound imaging of the mouse and highlights what could be the forthcoming advances.
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BACKGROUND: Protease nexin-1 (PN-1) is an important physiological regulator of thrombin in the brain. PN-1 is also present in aortic smooth muscle cells and may thus participate in vascular biology. However, little is known about its function in the vessel wall. OBJECTIVES: In this study, we investigated the effect of PN-1 overexpression in smooth muscle cells (SMCs), on their sensitivity to thrombin, and their capacity for adhesion, spreading and migration. RESULTS: Two clones exhibiting a two- to threefold increase in PN-1 expression were selected and compared with untransfected and mock-transfected cells. Overexpression of PN-1 was observed to inhibit thrombin-induced cell responses as indicated by a twofold decrease in induction of PAI-1 expression, a decreased calcium mobilization in response to low thrombin concentrations and a twofold increase in the capacity to inhibit thrombin catalytic activity. Overexpression of PN-1 did not modify adhesion, spreading, and migration of SMCs on type I collagen. In contrast, SMCs overexpressing PN-1 exhibited a 40% reduction in adhesion, a 50% reduction in spreading and a complete absence of migration on vitronectin when compared with control SMCs. CONCLUSIONS: Our studies thus reveal that PN-1 is likely to play a critical role in regulating essential cell functions such as (i) thrombin-induced responses, which are dependent on its antiprotease activity, and (ii) adhesion, spreading, and migration, which are independent of its antiprotease activity and may be related to its interaction with other partners, such as vitronectin in the present case.
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OBJECTIVE: This multicenter phase III study compared the MEMID regimen (mitoxantrone, VP16, methylglyoxal, ifosfamide and dexamethasone) with CEOP, a CHOP-like regimen (cyclophosphamide, epirubicin, vincristine and prednisone), in elderly patients (> or =65 years) with aggressive non-Hodgkin's lymphoma (NHL). METHODS: One hundred and forty-nine patients were eligible, 72 in the MEMID arm and 77 in the CEOP arm. The primary endpoint was to compare overall survival (OS) between groups, and secondary endpoints were event-free survival (EFS), response rate and toxicity. RESULTS: Neutropenia (p < 10(-5)), anemia (p < 10(-5)) and thrombocytopenia (p = 0.0006) were significantly more frequent in patients who received MEMID. We observed an objective response rate of 55.5% in the MEMID arm and 64.9% in the CEOP arm (p = 0.24). The median OS and EFS were 15.4 and 8.5 months in the MEMID arm, and 20.3 and 10.5 months in the CEOP arm (p = 0.59 and 0.47), respectively. The median EFS was 15.4 months in the MEMID arm and 20.3 months in the CEOP arm (p = 0.59). CONCLUSION: The increased toxicity without survival benefit confirms the superiority of CHOP and CHOP-like regimens for elderly patient with aggressive NHL.
INTRODUCTION: Birmingham Children's Hospital (BCH) is the centre for a regional comprehensive cleft service attempting to implement the national guidelines for minimum standards of care. A national audit of cleft management (CSAG) found that 58% of alveolar bone grafts were successful; published series suggest that success rates can be of the order of 95%. We present the results of an audit of alveolar bone grafting over a 33-month period, after implementation. PATIENTS AND METHODS: A retrospective clinical process audit was taken from the hospital notes and an analysis of radiological outcome by Bergland score was obtained by two independent assessors. RESULTS: The audit highlighted the difficulties of integrating the increased clinical workload. Other difficulties included poorly standardised pre- and postoperative occlusal radiography, inconsistent orthodontic management and a lack of prospective data collection. An 81% success rate for alveolar bone grafting compares favourably to the CSAG study. Of 82 patients, 68 had sufficient data for a retrospective review; 21 were our own patients and 47 were referred into the centralised service. The success of bone grafting as defined by CSAG (including Bergland scores) is based on only two-thirds of the patients as many have their orthodontic treatment managed in more distant units and radiographs are much harder to obtain. Bone grafting later than age 11 years, was true for 28% (6/21) of our BCH patients and 46% (22/47) for those referred to our service. CONCLUSIONS: This audit demonstrates what has been achieved in a re-organised service in the context of Real Politik in the NHS and suggests the areas that require improvement.
OBJECTIVE: Acid production from sugars is one of the virulence factors of cariogenic bacteria. To eliminate this factor, many authors have suggested using sugar substitutes like xylitol, which is not fermented by most oral bacteria. The aim of this work was to investigate whether oral strains of lactobacilli unable to utilise xylitol could become able to utilise this polyol. DESIGN: Twenty-eight oral strains and six ATCC strains of lactobacilli were tested. None was initially able to produce acids from xylitol. Media containing only xylitol was used in order to see if an adaptation was possible. The acid production from xylitol was measured by recording the pH variations of the culture medium. The acids produced were identified by HPLC. RESULTS: After a 15-days culture, 10 strains produced acids. After a 40-days culture, 11 more strains produced acid. When acid production occurred, lactic, formic, acetic, propionic and butyric acids were the organic acids formed by all the strains. CONCLUSIONS: Adaptation of oral strains of lactobacilli to xylitol can occur in vitro.
OBJECTIVE: To present first-line thoracic surgery made possible by localization studies in three patients with ectopic parathyroid adenomas. DESIGN AND METHODS: Three patients with ectopic parathyroid tissue in the mediastinum were examined by ultrasound, technetium-99m sestamibi scintigraphy, computed tomography (CT), and venous catheterization with measurement of parathyroid hormone. Without previous cervical exploration, video-assisted thoracic surgery (VATS) was used in all cases to avoid the need for thoracic open surgical procedures. RESULTS AND CONCLUSIONS: The mediastinal parathyroid glands were all detected at scintigraphy, and CT and venous catheterization were helpful in anatomic and functioning characterization. All pathologic glands were successfully resected, with only one minor complication. VATS can safely remove a deep mediastinal parathyroid adenoma and avoid more aggressive open approaches. In an experienced referral center, systematic and sophisticated imaging studies may accurately identify and localize rare ectopic parathyroid adenomas, and avoid cervical surgery.
A NEW FORM OF MEDICAL IMAGING: Positron emission tomography (PET) is used for the non-invasive in vivo visualisation of biochemical cell processes. It reveals the metabolic characteristics of neoplastic lesions and hence their identification by compensating the lack of lesion specificity of radiological techniques. VARIOUS INDICATIONS: Using the current oncology marker, 18F-fluorodeoxyglucose (FDG), excellent results with PET have been established at all stages of neoplasia, notably for the diagnosis of initial malignancy and the identification of residual lesions and early detection of relapses. Moreover, the fact that the whole of the body can be explored makes PET the tool of choice in the control of the extension and operability of cancers. With the close correlation between imaging and the metabolism of the lesions, PET is the earliest and most precise for assessing the effects of treatment. LIMITS AND PERSPECTIVES: The existence of benign inflammatory FDG binding should lead to the development of markers of other metabolisms directly linked to cell proliferation. The lack of anatomical reference points characteristic of PET does not permit the precise localisation of the lesions detected and could be corrected by combining, in a single apparatus, the PET camera and an X scan, the anatomical resolution of which is irreplaceable. This type of equipment represents the development of a new branch of medical imaging, oncological imaging.
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Rituximab (chimeric anti-CD20 IgG1 monoclonal antibody) is effective in the treatment of relapsed/refractory low-grade lymphomas of B-cell origin as well as in diffuse large B-cell lymphoma. Several reports also demonstrated the efficacy of rituximab for the treatment of autoimmune cytopenia, especially for cold agglutinin disease. We report the first case, to our knowledge, of rituximab-related autoimmune hemolytic anemia. The pathophysiological mechanisms remain unknown, although the drug could act through massive cytokines liberation after destruction of CD20 positive cells by rituximab.
Numerous studies have demonstrated efficacy of imipenem-cilastatin, 50 mg/kg/day, as first line therapy in febrile patients with neutropenia of short duration consecutive to cytostatic chemotherapy. However, only two studies used low dosage of this antibiotic as 1.5 g/day, in prospective, double blind, randomized clinical trials, in this indication. Efficacy and tolerability of imipenem-cilastatin 0.5 g three times daily IV in 30-min infusions, as first-line empiric therapy, were retrospectively evaluated in our hematological unit. From January 1996 to September 2000, 30 neutropenic patients (12 females) with 45 febrile episodes were included. Median age was 57.5 years (31-75). Twenty-four of them had lymphomas, 4 solid tumors and 2 myelomas. There were 13 clinically documented infections, (CD, 28.8%), 16 microbiologically documented infections, (MD, 35.6%) and 16 febrile episodes corresponding to fever of unknown origin, (FUO, 35.6%). The median neutrophils count on nadir (n = 44), was 67/mm3 (8-369). The median duration of neutropenia was 5 days (3-15). Bacteremia was observed in 10 patients, urinary tract infection in 3 patients. The most frequently isolated microorganism was Escherichia coli. The overall success rate of the first line therapy was 66.7%. Adverse events were observed in 11.1% of the patients without necessity to stop treatment. The MD infections showed a lower rate of success compared with CD infections and FUO. These data were in accordance with the previous studies. The importance of number of microorganisms (p = 0.007) and of infected sites (p = 0.01) appeared as prognostic factors (univariate analysis). Although imipenem-cilastatin has been used in numerous studies as empiric broad-spectrum antibiotic therapy in the treatment of febrile neutropenic cancer patients, the exact dosage of this antibiotic is still not standardized. However, utilization of this antibiotic in monotherapy at low dosage seems to us to be safe and effective as usual dosage in the antimicrobial treatment ofthe febrile patients with post chemotherapy neutropenia of short duration.
Somatostatin (SRIF) receptors (sst) are present on normal pancreatic endocrine beta-cells. However, the use of SRIF analogs in the scintigraphic imaging of insulinomas and in the medical management of these tumors seems to be restricted to a subgroup of patients. The aim of this study was to determine the prevalence of sst expression in vitro and characterize sst subtype binding in insulinomas and its correlation with in vivo sst receptor scintigraphy (SRS). In vitro studies were performed on 27 insulinomas from 25 patients: 22 with benign and three with malignant tumors. Semiquantitative RT-PCR of sst mRNAs was performed for 20 of these insulinomas. Sst2 and sst5 were expressed in 70%, sst1 in 50%, and sst3 and sst4 subtypes only in 15-20% of the tumors. (125)I-Tyr(0)DTrp(8)SRIF(14) binding was assessed by quantitative autoradiography in 18 insulinomas, and competition experiments were performed with SRIF(14) and L797-591, L779-976, L796-778, L803-087, L817-818, selective agonists of the five sst subtypes, and BIM23244, a selective agonist of sst2 and sst5. Significant specific binding was observed in 72% of the insulinomas. Displacement experiments with ligands of higher affinity for each of the sst receptors revealed significant binding with the sst2 and sst5 ligands in 72%, sst3 in 44%, sst1 in 44%, and sst4 in 28% of cases. All insulinomas displaying sst2 binding were also sst5 sensitive. However, the ratio of sst5/sst2 displacement was variable and only equal to that for SRIF(14) in experiments with the sst2/sst5 agonist BIM23244. SRS was performed 10 times in nine patients; it detected 60% of the tumors, including metastases of a malignant insulinoma. All the tumors detected by SRS displayed high levels of (125)I-Tyr(0)DTrp(8)SRIF(14) binding. The mechanisms underlying the loss of expression of sst2/sst5 in a third of insulinomas remains to be determined, but this loss of expression may be involved in beta-cell dysfunction.
Primary hyperparathyroidism is due to an adenoma in 85% of cases. In 10% of cases, the parathyroid adenoma may be in an ectopic location. Ten per cent of these ectopic adenomas are located in the mediastinum. Imaging modalities performed in persistent or recurrent hyperparathyroidism include ultrasound, MIBI scintigraphy, venous blood sampling, helical CT and MRI. The authors report 3 cases of ectopic adenoma located in the mediastinum, where pre-operative diagnosis was confirmed using cardiac MRI sequences.
The isolation of lupeol, beta-sitosterol acetate and three quinolizidinic alkaloids, (+)-lupanine, (-)-sparteine and (-)-3 beta-hydroxy-13 alpha-tigloyloxy-lupanine (1), from the stem bark of Ormosia wayana is reported.
The Lactobacillus genus has been shown to be associated with the dental carious process, but little is known about the species related to the decay, although Lactobacillus rhamnosus is suspected to be the most implicated species. Conventional identification methods based on biochemical criteria lead to ambiguous results, since the Lactobacillus species found in saliva are phenotypically close. To clarify the role of this genus in the evolution of carious disease, this work aimed to find a rapid and reliable method for identifying the L. rhamnosus species. Methods based on hybridization with DNA probes and DNA amplification by PCR were used. The dominant salivary Lactobacillus species (reference strains from the ATCC) were selected for this purpose as well as some wild strains isolated from children's saliva. DNA profiling using semirandom polymorphic DNA amplification (semi-RAPD) generated specific patterns for L. rhamnosus ATCC 7469. The profiles of all L. rhamnosus strains tested were similar and could be grouped; these strains shared four common fragments. Wild strains first identified with classic methods shared common patterns with the L. rhamnosus species and could be reclassified. One fragment of the profile was purified, cloned, used as a probe and found to be specific to the L. rhamnosus species. These results may help to localize this species within its ecological niche and to elucidate the progression of the carious process.