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Biomedical subjects

C Herbert

Publications and source records attributed to C Herbert.

At least 19 recordsLinked to original sources
PubMed2003

Dissociation of T helper type 2 cytokine-dependent airway lesions from signal transducer and activator of transcription 6 signalling in experimental chronic asthma.

BACKGROUND: Type 2 T helper lymphocytes (Th2 cells) and their cytokine products are important in the pathogenesis of asthma. OBJECTIVE: To examine the contribution of the signal transducer and activator of transcription (STAT) 6 pathway, involved in Th2 cytokine signalling, to the development of lesions of chronic asthma. METHODS: BALB/c mice sensitized to ovalbumin were chronically challenged by inhalational of low mass concentrations of antigen for 6 weeks. Airway lesions in wild-type mice were compared with those in STAT6-deficient mice and in IL-4/13 double-deficient mice by histomorphometry and immunohistochemistry. Airway responses to methacholine were evaluated by whole-body plethysmography. Cytokine production by peribronchial lymph node cells was quantified by enzyme immunoassay. RESULTS: STAT6-/- mice developed a variety of airway lesions that were at least equivalent to those in wild-type mice, including accumulation of intraepithelial eosinophils and of chronic inflammatory cells in the lamina propria, subepithelial fibrosis and epithelial thickening. In addition, STAT6-/- mice exhibited exaggerated airway hyper-reactivity (AHR) compared to wild-type animals. This was despite a shift from a Th2 to a Th1 pattern of immunoglobulin production by plasma cells in the inflammatory infiltrate and diminished mucous cell hyperplasia/metaplasia, together with increased production of IFN-gamma by peribronchial lymph node cells, consistent with absence of signalling via the STAT6 pathway. In contrast, gene-targeted IL-4/13-/- mice exhibited markedly diminished eosinophil recruitment and airway remodelling, as well as absence of AHR. CONCLUSIONS: In this model, the effects of STAT6 deficiency were in marked contrast to the suppression of inflammation and AHR described in models of allergic bronchopulmonary inflammation. These results, which provide evidence of STAT6-independent AHR in an inhalational challenge model of chronic asthma, emphasize the critical effector roles of IL-4 and IL-13, as well as the need to use appropriate models to understand cytokine signalling pathways that may be potential therapeutic targets in asthma.

Animals↗
PubMed2003

Microarray-based method for combinatorial library sequence mapping and characterization.

Here we describe a DNA-chip-based method for high-throughput sequence mapping. This involves competitive hybridization between short and differentially labeled fluorescent oligonucleotide probes and glass-supported PCR products. Competition between an excess of oligonucleotide probes targeting the same sequence segment improves sequence discrimination and reduces sensitivity to experimental conditions such as probe concentrations, hybridization, and washing temperatures and durations. The method was found to be particularly adapted to sequence mapping of combinatorial libraries obtained by DNA shuffling between members of a gene family. We present an application of this technique for the characterization of recombination biases in combinatorial libraries used in directed evolution.

Base Sequence↗
PubMed2002

Role of interleukin-13 in eosinophil accumulation and airway remodelling in a mouse model of chronic asthma.

BACKGROUND: Interleukin-13 is believed to be important in asthmatic inflammation and airway hyper-reactivity. OBJECTIVE: To investigate the role of IL-13 in chronic asthma, using an improved experimental model of asthma that reproduces most of the morphological features of the human disease. METHODS: BALB/c mice or gene-targeted mice deficient in their ability to produce IL-13 or the IL-4 receptor alpha-chain (IL-4Ralpha) were sensitized to ovalbumin and exposed to aerosolized antigen for 30 min/day on 3 days/week for 6 weeks. Intraepithelial eosinophils, accumulation of chronic inflammatory cells in the airway wall, subepithelial fibrosis, epithelial hypertrophy and numbers of mucous cells were quantified histomorphometrically. Airway hyper-reactivity (AHR) to a cholinergic agonist was assessed by barometric plethysmography. RESULTS: Compared with wild-type animals, IL-13 -/- mice exhibited diminished accumulation of eosinophils and chronic inflammatory cells, as well as reduced subepithelial fibrosis, epithelial hypertrophy and mucous cell hyperplasia (P < 0.01 for all comparisons). In contrast, AHR was still demonstrable in IL -13 -/- mice. In IL-4Ralpha -/- mice the inflammatory response, subepithelial fibrosis and AHR were similar to wild-type mice, although the receptor-deficient mice had significantly less epithelial hypertrophy and mucous cell hyperplasia. CONCLUSION: These results imply a critical role for IL-13 in accumulation of intraepithelial eosinophils in chronic asthma, as well as in epithelial and subepithelial remodelling. In addition, they suggest that in chronic asthma, IL-13 may be capable of signalling via a pathway that does not involve IL-4Ralpha.

Animals↗
PubMed2002

[Influence of social and occupational class and area of residence on management and survival in patients with digestive tract cancer: a population study in the Calvados area (France)].

Several studies have shown socio-economic differences in cancer survival, low socio-economic level being associated with poor prognosis of cancer. The aim of the study was to investigate the influence of social environment on care procedures for treatment in cancer and to determine to what extent well-established socio-economic differences in cancer prognosis can be explained by such an influence. A retrospective analysis was conducted on patients having had a digestive cancer in the department of Calvados (France) between 1978 and 1990 collected by the local digestive cancer registry (1534 males and 1060 females). Jobless male and female farmers visited private specialists and were treated in specialized care centres at a rate two-fold lower than people in higher social classes. However, our results suggest that these variations do not explain all the influence of social environment on cancer survival either in males and females.

Aged↗
PubMed2001

Molecular characterization of CLPT1, a SEC4-like Rab/GTPase of the phytopathogenic fungus Colletotrichum lindemuthianum which is regulated by the carbon source.

The gene CLPT1 (Colletotrichum lindemuthianum Protein Transport 1) encoding a Rab/GTPase was isolated from the filamentous fungus Colletotrichum lindemuthianum, the causal agent of bean anthracnose. At the amino acid level, CLPT1 shows between 54 and 80% identity to SEC4-like proteins, a class of molecules required for intracellular vesicular transport in yeasts. In particular, typical SEC4 domains involved in nucleotide binding and membrane attachment are present in the CLPT1 sequence. Functional identity of CLPT1 with SEC4 was confirmed by complementation of the Saccharomyces cerevisiae sec4-8 mutation. This is the first report of a gene involved in the control of intracellular vesicular trafficking in a phytopathogenic fungus. RNA blot analyses of CLPT1 expression were performed during in vitro growth of the fungus on synthetic media containing glucose or pectin, as single carbon source. The accumulation of CLPT1 mRNA was strongly increased on pectin, a plant cell wall polysaccharide that induces the production of extracellular pectinases, whereas the level of CLPT1 mRNA was below the detection threshold on glucose. These results suggest that CLPT1 is mainly involved in protein secretion and that the production of extracellular enzymes potentially involved in pathogenesis in filamentous fungi is sustained by induction of the genes involved in the secretory machinery.

Amino Acid Sequence↗
PubMed2001

Estimation of colorectal cancer prevalence in France.

The prevalence in France of patients with colorectal cancer was estimated using data from five population-based cancer registries. At the end of 1994, the number of cases diagnosed in France no more than 5 years before was approximately 95000, of whom 12180 had suffered metastasis and 9746 a local recurrence. This type of cancer is the most common in both men and women and these results enable the need for care or surveillance to be evaluated more accurately.

Adult↗
PubMed2001

Correlations between the duration of pain and the success of shock wave therapy.

Patients who have had successful treatment for either chronic heel pain (plantar fasciitis) or humeral epicondylitis subsequently were evaluated for a comparable problem in the contralateral heel or elbow. Patients who had experienced symptoms in the contralateral heel or elbow for a shorter period were less likely to have a positive result from shock wave therapy than those patients who had received treatments for more chronic symptoms.

Adult↗
PubMed2001

Stage of extension and treatment for colorectal cancer after a negative test and among non-responders in mass screening with guaiac faecal occult blood test: a French experience.

Despite its proven efficacy in three randomized trials, the relevance of mass screening for colorectal cancer using the guaiac faecal occult blood test is still debated. The low sensitivity of the test and the poor participation rate, especially in France, are major obstacles to its effectiveness. The aim of our study was to characterize cancers occurring after a negative test and among non-participants in the screening programme organized in the French department of Calvados. Cancers in the negative test group had a later stage of extension than subjects testing positively but an earlier stage of extension than cancers in the reference group, which were not different from those of non-responders. The proportion of resection for non-responders was significantly lower than that for participants, whatever the test result (P < 0.001), and lower than that for reference subjects (P < 0.05). There was no difference in treatment between negative and positive responders. Negative responders did not have a delayed cancer diagnosis or a worse condition of treatment than people who were not screened. Low sensitivity reduced the efficacy of colorectal cancer screening but did not seem to increase the potential to do harm.

Aged↗
PubMed2001

Making decisions about cancer screening when the guidelines are unclear or conflicting.

OBJECTIVE: Our purpose was to determine the factors involved in the cancer screening decisions of family physicians in situations where the clinical practice guidelines are unclear or conflicting as opposed to when they are clear and uncontroversial. STUDY DESIGN: We analyzed discussions with focus groups using a constant comparative approach. POPULATION: A total of 73 family physicians in active practice participated in 10 focus groups (1 urban group and 1 rural group in each of 5 Canadian provinces). OUTCOME MEASURES: Our main outcome measures were participants' perceptions regarding cancer screening when the guidelines were unclear or conflicting. RESULTS: We propose a model of the determinants of cancer screening decision making with regard to unclear and conflicting guidelines. This model is rooted in the physician-patient relationship, and is an interactive process influenced by patient factors (anxiety, expectations, and family history) and physician factors (perception of guidelines, clinical practice experience, influence of colleagues, distinction between the screening styles of specialists and family physicians, and the amount of time and financial costs involved in performing the maneuver). CONCLUSIONS: Our model is unique, because it is embedded in the physician-patient relationship. Ultimately, a modified model could be used to design interventions to assist with the implementation of preventive services guidelines.

Adult↗
PubMed2001

[Malignant mesothelioma in Basse-Normandie, a French population study. Descriptive analysis, prognostic factors and survival].

BACKGROUND: Malignant mesothelioma is a pleural and/or peritoneal tumor closely related to asbestos exposure, and its incidence should continue to increase during the first two decades of the 21(rst)century. The main prognostic factors described for this tumor are older age, sex, tumor stage and histological type. The aim of this study was to assess the incidence of pleural and peritoneal malignant mesothelioma in the County of Basse-Normandie (France), as well as their epidemiological characteristics, and the prognostic factors related to survival duration. METHODS: Cases were identified through repeated inquiries among all chest physicians and pathologists of the County of Basse-Normandie. A special care was taken in the validation of the diagnosis of each case. Incidence of mesothelioma was determined according to sex and age (5 years categories). Qualitative and quantitative variables were compared with the use of chi-square or Student's t tests respectively. Survival rate was calculated by Kaplan-Meier method, and prognostic factors were studied by means of Cox model. RESULTS: Study population consisted in all 80 malignant mesothelioma cases diagnosed in Basse-Normandie between the 1(rst) of September 1995 and the 31(rst) of August 1999. Annual incidence rates of pleural mesothelioma were 1.1/100 000 in men and 0.23/100 000 in women; annual incidence rates for peritoneal mesothelioma were 0.21/100 000 in men and 0.13/100 000 in women. Asbestos exposure was present in 63 cases (78.8%). The study of geographic distribution of mesothelioma cases revealed the influence of the main asbestos industrial settings, as well as the numerous scattered cases related to other occupational exposure. Mean survival duration was 9 months for pleural mesothelioma and 5 months for peritoneal mesothelioma. After adjustment on age, death risk was higher in asbestos-exposed than in non asbestos-exposed cases. CONCLUSION: This study confirms that malignant mesothelioma is closely related to asbestos exposure, but not only in main asbestos industrial settings. It suggests that asbestos exposure may take place among prognostic factors of this tumor.

Age Factors↗
PubMed2001

Use of morphine for pain after intracranial surgery.

Intramuscular codeine is the most regularly prescribed analgesia for post-surgery craniotomy patients. Morphine is avoided for this patient group because of fears of side-effects. A literature search found evidence that titrated morphine has no inherent risks if patients are well observed.

Analgesics, Opioid↗
PubMed2000

Novel therapeutic nano-particles (lipocores): trapping poorly water soluble compounds.

The development of stable spherical lipid-coated drug particles that are termed 'lipocores' is reported here. Unlike conventional lipid-based particles (i.e. liposomes, emulsions, micelles), these particles are comprised solely of a core of a poorly water soluble drug surrounded by polyethyleneglycol conjugated lipid (PEG-lipid) and are formed via a 'kinetic' trapping process. These lipocore particles were made with the acyl chain of 16 carbon length (C16) acyl-chain derivatives of paclitaxel or vinblastine and with the polyene antifungal hamycin. Formation of the particles occurred regardless of the type of PEG-phospholipid used (i.e. acyl chain length, chain saturation, and polymer length) and could also be formed with the negatively charged lipid N-glutaryl-dioleoyl-phosphatidylethanolamine (DOPE-GA). Images from both freeze-fracture electron microscopy and electron cryo-microscopy revealed solid spherical structures with no internal lamellae for the PEG-lipid particles made with the C16 derivatives of paclitaxel (BrC16-T) or vinblastine (C16-Vin). From a solute distribution study of lipocores made with BrC16-T and distearoyl-phosphatidylethanolamine-PEG2000 (DSPE-PEG2000), the particles were found to have no measurable aqueous captured volume. Fluorescence anisotropy and order parameter measurements revealed the core material of these particles to be highly immobilized. The mole ratio of BrC16-T:lipid in the lipocores was typically > 90: < 10 and as high as 98:2, and the refrigerated lipocores were stable for several months. BrC16-T/DSPE-PEG2000 lipocores of 50-100 nm particle size were far less toxic than paclitaxel (Taxol) after intraperitoneally (i.p.) or intravenously (i.v.) administration in mice and were active against i.p. and subcutaneously (s.c.) planted human (OvCar3) ovarian carcinoma grown in SCID mice. It is believed the high drug:lipid ratio, the stability, and therapeutic efficacy of these novel particles make them a paradigm for delivery of poorly water soluble drugs and/or their hydrophobic derivatives.

Animals↗
PubMed1999

Colorectal cancer after a negative Haemoccult II test and programme sensitivity after a first round of screening: the experience of the Department of Calvados (France).

Colorectal cancers emerging after a negative Haemoccult II are described in the context of a first round of mass screening in the Department of Calvados (France), from April 1991 to the end of December 1994. People with a cancer occurring after a negative test until 31 December 1995 were identified by a local cancer registry. Incidence was calculated and the programme sensitivity was estimated. The incidence of cancer emerging after a negative test was 57.7 per 100000, i.e. half of the calculated incidence in the reference group (141.6 per 100000). These cancers did not differ from those of either the non-responder or reference groups, in particular for the stage of extension. The programme sensitivity was globally higher than that estimated in European trials: 77.2, 66.3 and 55.9%, 1, 2 and 3 years after the test respectively. Programme sensitivity was higher for distal colon cancer 1 year after the test, which is probably due to the relatively slow growth of this subsite.

Aged↗
PubMed1999

Evidence of improving survival of patients with rectal cancer in france: a population based study.

BACKGROUND: Over the past 20 years there have been many changes in the management of rectal cancer. Their impact on the overall population is not well known. AIMS: To determine trends in management and prognosis of rectal cancer in two French regions. SUBJECTS: 1978 patients with a rectal carcinoma diagnosed between 1978 and 1993. METHODS: Time trends in treatment, stage at diagnosis, operative mortality, and survival were studied on a four year basis. A non-conditional logistic regression was performed to obtain an odds ratio for each period adjusted for the other variables. To estimate the independent effect of the period a multivariate relative survival analysis was performed. RESULTS: Over the 16 year period resection rates increased from 66.0% to 80.1%; the increase was particularly noticeable for sphincter saving procedures (+30.6% per four years, p=0.03). The percentage of patients receiving adjuvant radiotherapy increased from 24.0% to 40.0% (p=0.02). The proportion of patients with Dukes' type A cancer increased from 17. 7% to 30.6% with a corresponding decrease in those with more advanced disease. Operative mortality decreased by 31.1% per four years (p=0.03). All these improvements have resulted in a dramatic increase in relative survival (from 35.4% for the 1978-1981 period to 57.0% for the 1985-1989 period). CONCLUSIONS: Substantial advances in the management of rectal cancer have been achieved, but there is evidence that further improvements can be made in order to increase survival.

Adolescent↗
PubMed1999

[Reporting of resected colonic carcinomas. Assessment of practices in 8 French counties in 1995].

OBJECTIVES: The objective of this work was to study the reporting of resected colonic carcinomas and to compare them with Consensus Guidelines published in January 1998. METHODS: The study included 535 colonic carcinomas collected in 8 French registries in 1995, and chosen by drawing lots. For each report, the presence of the information requested by the Guidelines was looked for. Three synthetic variables were built: 2 scores and one qualitative at 2 classes. The influence of patients, tumour and health care system's characteristics was analysed on the 3 dependent variables. RESULTS: Some important variations were observed for information's percents in reporting. In monovariate analysis, scores were significantly influenced by cancer's sub-location, area of patient's residence, surgical center, type of laboratories and pathologist case volume. In multivariate analysis, significant heterogeneity in practices remained between geographical areas. Types of laboratories and pathologist case volume affected differently dependent variables. CONCLUSION: This study shows the necessity to assess the practices before consensus because of the impact of pathological forms in therapeutic decisions and variations observed.

Aged↗
PubMed1999

[Organized screening of colorectal cancer in France. System of care and professional logistics].

The preservation or the amelioration of the health of individuals and populations does not only depend on the activity of the medical profession. It largely depends on public health policies. Screening for cancers illustrates how difficult it is to organise an action of public health within a health care system of liberal tradition in France. Through the example of screening for colorectal cancer, this article proposes to identify the mechanisms by which the system of health care determines the methods of organisation of mass cancer screenings. Through interviews carried out among the organisers of five colorectal cancer screening campaigns, we identified three models on which French screening campaigns are based: an administrative model, a medical model and a mixed model. Each of these models represents a different adaptation of the organisation of mass screening to the health care system in place in France. The interests of the concerned professional groups confront each other and the collective interest. It seems that to integrate such an approach to public health in a system dominated by payment per act is doomed to fail. Today, France can no longer avoid a modification of its health care system and of its nomenclature if it wants to improve the feasibility of cancer screening programmes and increase their chance of success.

Attitude of Health Personnel↗