The future for the field of sports medicine.
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Evidence-Based Medicine↗
Biomedical subjects
C Martin
Publications and source records attributed to C Martin.
Detection of 11 germline inactivating TP53 mutations and absence of TP63 and HCHK2 mutations in 17 French families with Li-Fraumeni or Li-Fraumeni-like syndrome.
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Checkpoint Kinase 2↗
Expression profile of human herpesvirus 8 (HHV-8) in pyothorax associated lymphoma and in effusion lymphoma.
AIMS: Pyothorax associated lymphoma (PAL) occurs in a clinical setting of longstanding pyothorax or chronic inflammation of the pleura. Like primary effusion lymphoma, it has an association with Epstein-Barr virus (EBV), and is confined to the pleural cavity, but has differing morphological and phenotypic features. Human herpesvirus 8 (HHV-8) has been consistently reported in primary effusion lymphoma. This study examines the immunophenotype of two European cases of PAL, investigates the presence of HHV-8 and its expression profile, and assesses whether PAL is similar to other effusion lymphomas. METHODS: Material was obtained from two European cases of PAL. Immunocytochemical analysis was performed using antibodies against CD45, CD20, CD79a, CD45RAA, CD3, CD43, CD45RO (UCHL1), CD30, BCL-2, CD68, epithelial membrane antigen (EMA), BCL-6, p53, Ki-67, kappa light chain, lambda light chain, and the EBV antigens latent membrane protein 1 (LMP-1) and EBV encoded nuclear antigen 2 (EBNA-2). The cases were examined for HHV-8 by means of polymerase chain reaction in situ hybridisation (PCR-ISH), solution phase PCR, in situ hybridisation (ISH), and real time quantitative TaqMan PCR to HHV-8 open reading frame 26 (ORF-26) and viral (v) cyclin encoding regions. The expression profile of HHV-8 in PAL and in BC-1 and BC-3 cells was assessed by RNA TaqMan PCR to the HHV-8 genes encoding v-cyclin, v-IL-6, and G protein coupled receptor (GPCR). RESULTS: Both cases expressed CD24, CD20, CD79a, BCL-2, light chain restriction, and high Ki-67 staining. EBV was identified by EBER-ISH in one case. HHV-8 was not identified by solution phase PCR, but was detected by PCR-ISH (sensitivity of 1 viral genome copy/cell) in 35% of the cells and by TaqMan PCR, which showed 50-100 HHV-8 copies/2,000 cell genome equivalents (sensitivity of 1 viral genome in 10(6) contaminating sequences). HHV-8 v-IL-6, v-cyclin, and GPCR encoded transcripts were identified using RNA TaqMan PCR. v-IL-6 was high in PAL and in BC-1 and BC-3 cells. CONCLUSION: The presence of HHV-8 in one of two patients with PAL raises interesting questions in relation to the pathobiology of the condition. Clearly, the results indicate that HHV-8 is not an obligate pathogen, necessary for the effusion phenotype, but might contribute to it by its secretion of specific cytokines.
Aged↗
Changes in airway resistance by simultaneous exposure to TNF-alpha and IL-1beta in perfused rat lungs.
Tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta are formed simultaneously under inflammatory conditions such as asthma and acute respiratory distress syndrome. Here we investigated the effects of TNF-alpha (10 ng/ml) and/or IL-1beta (10 ng/ml) in isolated blood-free perfused rat lungs. In lungs precontracted with methacholine, IL-1beta alone and IL-1beta/TNF-alpha decreased airway resistance 10 min after administration, whereas TNF-alpha alone had no effect. In untreated lungs, airway resistance was unaltered by either cytokine alone but started to increase 40 min after treatment with both cytokines together, indicating bronchoconstriction. The bronchoconstriction was accompanied by a steroid-sensitive increase in cyclooxygenase (COX)-2 mRNA expression and thromboxane formation. The cytokine-induced bronchoconstriction was blocked by the thromboxane receptor antagonist SQ-29548, indomethacin, the selective COX-2 inhibitor NS-398, and the steroid dexamethasone. We conclude that IL-1beta has an early bronchodilatory effect (after 10 min) that is unchanged by TNF-alpha. However, at later time points (after 40 min), IL-1beta and TNF-alpha in concert cause a COX-2- and thromboxane-dependent bronchoconstriction. Our findings show that TNF-alpha and IL-1beta exert complex and time-dependent effects on lung functions that cannot be predicted by studying each cytokine alone.
Airway Resistance↗
Exogenous reinfection with tuberculosis on a European island with a moderate incidence of disease.
The frequency and determinants of exogenous reinfection and of endogenous reactivation of tuberculosis in patients previously treated are poorly understood. In Gran Canaria Island, Spain, between 1991 and 1996, 962 tuberculosis cases were confirmed by culture. Drug susceptibility testing was performed on available bacterial isolates and IS6110-based RFLP genotyping was carried out. Twenty-three patients (2.4%) had two positive cultures separated by at least 12 mo, 18 of whom had bacterial DNA available for genotypic analysis. The initial and final isolates from eight (44%) were different genotypes, indicating exogenous reinfection. Six of them were retreated after cure and two retreated after default. Six were HIV seronegative and two were HIV seropositive. Endogenous reactivation was seen in the remaining 10 patients of whom eight were retreated after default and two after cure. Three of the eight (38%) being retreated after default developed multidrug resistance. One genotype was responsible for a second episode of tuberculosis in five cases, three exogenous reinfections and two endogenous reactivations. In the context of a moderate incidence of tuberculosis, exogenous reinfection is an important cause of TB recurrence, even in HIV-seronegative patients.
Adult↗
Immediate allergic response in small airways.
The role of small airways in the immediate allergic response is largely unknown. We therefore used the model of precision-cut lung slices (PCLS) in combination with quantitative videomicroscopy to study the early allergic response to allergen in airways ranging from 50 to 900 microm. After PCLS from untreated Wistar rats had been passively sensitized for 16 h with serum from sensitized Brown Norway rats, exposure to 0.1% ovalbumin resulted in an immediate allergic response. Both extent (r = 0.74, p < 0.0001) and velocity (r = 0.49, p < 0.0001) of the allergen-induced bronchoconstriction increased with decreasing airway size. In addition, we observed that smaller airways not only contracted stronger and quicker, but that they also relaxed faster, suggesting that smaller airways are more reactive in principle. The allergen-induced bronchoconstriction in PCLS was prevented by the serotonin receptor antagonist ketanserin (IC(50) 6 nM), but not by antagonists directed against histamine, acetylcholine, PAF, or endothelin receptors, or by cyclooxygenase or lipoxygenase inhibitors. Like allergen, serotonin provoked responses that were stronger in smaller airways. These findings suggest that the immediate allergic response in rat PCLS depends largely on serotonin and that this response can occur in nearly all airway generations, but is most pronounced in the smallest airways, that is, the terminal bronchioles.
Allergens↗
Cytokine-induced bronchoconstriction in precision-cut lung slices is dependent upon cyclooxygenase-2 and thromboxane receptor activation.
Cytokines play an essential role in the regulation of inflammatory responses. The effects of cytokines on lung functions are less well known and their study in vivo is complicated by the attraction of leukocytes to the inflamed sites. Recently the model of precision-cut lung slices was developed, where viable lung slices with an intact microanatomy are taken into culture and where bronchoconstriction can be followed by observing single airways under the microscope. We used this model to study the direct effects of cytokines on airway tonus in the absence of blood-derived leukocytes. Incubation of precision-cut lung slices with a mixture of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and interferon (IFN)-gamma resulted in contraction of airways, which was accompanied by expression of cyclooxygenase (Cox)-2 and thromboxane release into the supernatant. The thromboxane receptor antagonist SQ29548 completely prevented the cytokine-induced bronchoconstriction, whereas the 5-lipoxygenase inhibitor AA681 had no effect on cytokine-induced bronchoconstriction. Preventing the expression of Cox-2 by dexamethasone or blocking Cox-2 activity with the selective Cox-2 inhibitor NS398 attenuated both thromboxane formation and bronchoconstriction. Incubation of lung slices with each of the cytokines alone caused no bronchoconstriction; in fact, IL-1 alone rather dilated the airways. However, simultaneous incubation with TNF and IL-1beta caused a bronchoconstriction that was not further enhanced by IFN-gamma. We conclude that TNF-alpha and IL-1beta synergistically cause bronchoconstriction by induction of Cox-2 and subsequent activation of the thromboxane receptor. Our study raises the possibility that TNF and IL-1 may contribute to bronchospasm during inflammatory lung diseases.
Animals↗
Real-time quantitative analysis of E-cadherin expression in ret/PTC-1-activated thyroid neoplasms.
Papillary thyroid carcinoma (PTC), the most common variety of thyroid cancer, is found in a variety of morphologic variants, usually grows slowly, and is clinically indolent, although rare, aggressive forms, with local invasion or distant metastases, occur. Our group has previously demonstrated an association between Hashimoto thyroiditis and ret/PTC-1 activation, and have hypothesised that c-ret activation might be implicated in immune reaction to thyroid epithelium. The objective of this study was to examine expression of the cellular adhesion molecule, E-cadherin, in various thyroid tumor types and Hashimoto thyroiditis in the context of ret/PTC-1 positivity by using laser capture microdissection and TaqMan reverse transcription-polymerase chain reaction (RT-PCR). Variable down-regulation of E-cadherin among carcinomas was demonstrated, with anaplastic carcinomas showing little or no expression. Follicular thyroid carcinomas consistently had significantly decreased E-cadherin expression compared with papillary thyroid carcinomas. The ret/PTC-1-positive papillary thyroid carcinoma (PTCret+) and Hashimoto thyroiditis cases had consistently lower E-cadherin expression levels than the corresponding ret/PTC-1-negative papillary carcinomas (PTCret-), suggesting not only an association between ret activation and the loss of cellular adhesion but also, more significantly, an association between papillary thyroid carcinoma and Hashimoto thyroiditis.
Cadherins↗
Role of glycopeptides in the treatment of septic complications after cardiac surgery.
Agents like Staphylococcus epidermidis and Staphylococcus aureus are common agents in both early and late prosthetic valve endocarditis (PVE). Streptococci, especially vividans and enterococci are more apt to occur late. Diphtheroids and gram-negative bacteria are also frequent in early and late PVE. Fungi are found at a frequency of 5 to 8% and a variety of unusual organisms are found in individual case reports. Treatment is based on parenteral therapy with a bactericidal agent that can achieve trough serum levels in excess of 8-10 X MICs of the infecting organisms. Initially the antibiotic selection should be active against the most common isolates. Because most S. epidermidis are beta-lactam-resistant, vancomcyin must be part of the initial empiric regimen. Vancomycin should be combined with rifampin or an aminoglycoside (usually gentamicin) or both. When there is a high level of resistance to aminoglycoside, vancomycin may be used alone until susceptibility data are available and then rifampin can be given together with an aminoglycoside or a quinolone to which the organism is susceptible. The aminoglycoside should be given for a maximum of 2 weeks, to avoid nephrotoxicity, and vancomycin for 6 weeks. Surgery is required in case of major emboli, hemodynamic decompensation, and uncontrolled infection. The presence of bacteremia for more than 1 week may warrant surgical intervention but, if the patient appears to be well and without emboli or hemodynamic problems, serum levels of antibiotic, particularly vancomycin, should be evaluated. Dosage regimen should be modified to achieve trough levels of vancomycin between 15 to 20 microg/ml. Use of vancomycin by continuous infusion may be considered with a targeted blood concentration of 15 to 20 microg/ml.
Anti-Bacterial Agents↗
Angiogenesis inhibition in the in vivo antineoplastic effect of manumycin and paclitaxel against anaplastic thyroid carcinoma.
Our laboratory has investigated the anticancer effects of combined manumycin (a farnesyltransferase inhibitor) and paclitaxel (a microtubule inhibitor) against anaplastic thyroid carcinoma (ATC). In this study we reported the in vivo efficacy of this combination against ATC cells and the lack of toxicity of this treatment in mice. We observed that manumycin-treated tumors looked paler than both control and paclitaxel-treated tumors. We hypothesized that angiogenesis inhibition mediated part of the in vivo effect of manumycin. This hypothesis was supported by the findings that manumycin significantly inhibited angiogenesis (as directly demonstrated by measurement of hemoglobin content and vascular area) in Matrigel implanted into mice, that manumycin decreased the vascular endothelial growth factor in hypoxic ATC cells, and that both manumycin and paclitaxel inhibited endothelial cell proliferation. Interestingly, inhibition of endothelial tubule formation in Matrigel was enhanced by combining manumycin and paclitaxel. As angiogenesis and tumor growth are continuous processes, we investigated the effect of sustained delivery of manumycin and found that paclitaxel plus slow release manumycin (13.25 mg/kg x week) inhibited ATC xenografts more than paclitaxel plus intermittent manumycin (15 mg/kg x week). In conclusion, manumycin plus paclitaxel is an effective combination against ATC, and inhibition of angiogenesis plays a role in the antineoplastic effect of this combination.
Animals↗
The diving behaviour of green turtles undertaking oceanic migration to and from Ascension Island: dive durations, dive profiles and depth distribution.
Satellite telemetry was used to record the submergence duration of green turtles (Chelonia mydas) as they migrated from Ascension Island to Brazil (N=12 individuals) while time/depth recorders (TDRs) were used to examine the depth distribution and dive profiles of individuals returning to Ascension Island to nest after experimental displacement (N=5 individuals). Satellite telemetry revealed that most submergences were short (<5 min) but that some submergences were longer (>20 min), particularly at night. TDRs revealed that much of the time was spent conducting short (2-4 min), shallow (approximately 0.9-1.5 m) dives, consistent with predictions for optimisation of near-surface travelling, while long (typically 20-30 min), deep (typically 10-20 m) dives had a distinctive profile found in other marine reptiles. These results suggest that green turtles crossing the Atlantic do not behave invariantly, but instead alternate between periods of travelling just beneath the surface and diving deeper. These deep dives may have evolved to reduce silhouetting against the surface, which would make turtles more susceptible to visual predators such as large sharks.
Animal Migration↗
The Internet and hospital marketing strategy: a survey.
This project, which was conducted in the U.S. using a large number of healthcare organizations, is an attempt to discover if we can find any evidence of the impact of marketing theories on the real world of healthcare organizations. This paper addresses three major themes: Do healthcare organizations have an Internet strategy? Are they using the Internet in a strategic fashion? Can we identify any difference among the sectors concerning the strategic use of the Internet? Finally, implications for further research and health care practices are highlighted as well.
Health Care Surveys↗
Classroom contexts: connections between class size and within class grouping.
BACKGROUND: There has been a vigorous debate for many years about the educational effects of class size differences, but even if differences have an impact on pupils' academic progress this still leaves unanswered important questions about what mediates the effect. AIMS: This paper is informed by a classroom contextual perspective, and examines associations between class size and within class groupings (in terms of size and number of groups, adult presence in groups, and type of interaction between grouping members). Age differences in these relationships are also explored. SAMPLES: The quantitative study is based on analysis of 3157 groupings, from 672 Reception, Year 2 and Year 5 classes in 331 schools. The qualitative study was based on 12 classes in 8 case study schools, and questionnaire responses completed by over 100 class teachers. METHODS: Links between size of class and within class groupings were examined on the basis of a 'grouping mapping survey', in which teachers at a given time in the school day provided information on group size and number, adult presence, and type of interaction between pupils, and complementary qualitative analyses of data from teacher-completed questionnaires, and interviews. RESULTS: The number of groups in a class increased with the size of the class. Over all three year groups, small classes had on average just over three groups, while large classes approached six groups. The size of groups in the class decreased with size of class. In class sizes over 25, pupils were more likely to be in a large group of 7-10, while in classes under 25 they were more likely to be in whole class groupings. Qualitative analyses showed that teachers felt that groups of 7-10 pupils had negative educational effects, for example, in terms of the quality and quantity of teaching and children's concentration and contribution in groups. CONCLUSIONS: Results suggest that the effects of class size can be best seen as through the size and number of groups, which will then have implications for learning experiences. So while debate about size of class has often been in terms of reduced size of class resulting in pupil academic gains, it is also important educationally to consider within class grouping size and number, and their effects.
Child↗
Long-term arterial cannulation in ICU patients using the radial artery or dorsalis pedis artery.
STUDY OBJECTIVES: To evaluate the rate of arterial thrombosis and catheter-related infection following radial artery or dorsalis pedis artery (DPA) cannulations lasting > or = 4 days. DESIGN: Prospective, observational study of two cohorts of ICU patients. SETTING: ICU of a university hospital. PATIENTS: In a first group of 131 consecutive patients, the DPA was selected for arterial cannulation. In the second group, 134 consecutive patients were considered for radial artery cannulation. MEASUREMENTS AND RESULTS: In the DPA group, the overall success rate for catheter placement was 85%. Patients were cannulated for 16 +/- 5 days (mean +/- SD). In the radial artery group, the overall success rate was 97.7% (129 of 132 patients; p < 0.0001 vs DPA group). Patients were cannulated for 13.3 +/- 4.0 days. In both groups, no signs of ischemia were detected at the clinical examination. In the DPA group, no thrombosis was detected at the angiographic examination in 21 patients (38%), a thrombosis without vessel obstruction was observed in 21 patients (31%), and a thrombosis with vessel obstruction was observed in 21 patients (31%). In the radial artery group, no thrombosis was observed in 31 patients (24%; not significant vs DPA group), a partial thrombosis was found in 73 patients (57%), and a total thrombosis with vessel obstruction was found in 25 patients (19%). Two cases of catheter-related infection were observed in the DPA group. In the radial artery group, four cases of catheter-related infection were diagnosed vs DPA group (not significant). CONCLUSIONS: The rate of serious complications was similar for both sites of arterial cannulation. Accepting a 12.7% lower rate of successful placement, the DPA route provides a safe and easily available alternative when radial arteries are not accessible.
Catheterization, Peripheral↗
Prevention of nosocomial urinary tract infection in ICU patients: comparison of effectiveness of two urinary drainage systems.
STUDY OBJECTIVES: To determine whether the rate of acquisition of bacteriuria differs between the use of a complex closed drainage system (CCDS) with a preattached catheter, antireflux valve, drip chamber, and povidone-iodine releasing cartridge, and a two-chamber open drainage system (TCOS) in ICU patients. DESIGN: Prospective, nonrandomized, controlled trial. SETTING: Medical/surgical/trauma ICU in a university hospital. PATIENTS: Two hundred twenty-four ICU patients requiring an indwelling urinary catheter. INTERVENTION: We compared the rate of acquisition of bacteriuria in two groups of consecutive patients (n = 113 and n = 111, respectively) who underwent bladder catheterization with a TCOS during the first 6 months and with a CCDS during the next 6 months. Urinary catheters were managed by a team of trained nurses following the same written protocol. No prophylactic antibiotics were administered, either during management of catheter placements or catheter withdrawal, but 75% of patients received one or more antimicrobial medications for treatment of infected sites other than the urinary tract. Urine samples were obtained weekly for the duration of catheterization and within 24 h after catheter removal, and each time symptoms of urinary infection were suspected. Only patients who required an indwelling catheter for > 48 h were evaluated. MEASUREMENTS AND RESULTS: There was no statistical difference in the rate of bacteriuria between the two groups. Bacteriuria occurred in 11.5% and 13.5% of patients, and was diagnosed on day 14 +/- 8 and 13 +/- 9 of catheterization (mean +/- SD) for the TCOS and the CCDS, respectively. A CCDS cost $3 (US dollars) more than the TCOS. CONCLUSIONS: To our knowledge, this is the first study to compare the effectiveness of a TCOS and a CCDS in ICU patients. No differences were noted between the two systems (alpha = 0.05). The higher cost of a CCDS is not justified for ICU patients.
Bacteriuria↗
The development and fine structure of Lankesterella cf. dicroglossi (Apicomplexa: Lankesterellidae) infecting frogs in Niger, West Africa.
One of four Hoplobatrachus occipitalis (Günther, 1859) frogs received from Niger, West Africa was heavily infected with Lankesterella blood and pre-erythrocytic stages. Infected blood and tissues from this frog were force-fed to the remaining three frogs. Two survived to necropsy on days 14 and 27 post-feeding and were found to be infected with gamogonic and oogonic stages, respectively. The source of infection is inconclusive, as a natural origin cannot be excluded. Microgamont, macrogamont, oocyst and sporozoite structure and fine structure are described and found to conform in general, but not in detail, to previous descriptions. Gamonts and oocysts occurred predominantly in the liver and spleen. Walled sporulating oocysts were situated within macrophage centres. Oocysts yielded a progeny of 32 sporozoites. Pre-erythrocytic sporozoites developed within expanded inclusions, within their host cell, from which they massively invaded the liver and spleen, and to a lesser extent the lungs and kidneys. Sporozoites occurred in a parasitophorous vacuole in the erythrocytes. Conspecificity with Lankesterella dicroglossi Paperna et Ogara, 1996 reported from the same host species in Kenya remains uncertain due to several structural and developmental differences.
Animals↗
Assessment of axillary lymph node involvement in small breast cancer: analysis of 893 cases.
Axillary nodal involvement (ANI) remains an essential prognostic factor for breast cancer patients, as it implies the necessity of systemic adjuvant treatment and locoregional irradiation. Axillary dissection (AD) contributes to improved local disease control and may increase survival. However, AD results in a 10%-25% incidence of long-term side effects, particularly lymphedema. Moreover, many small primary lesions with low risk of ANI are now discovered by screening, and it is not clear whether AD should be used routinely in all such patients. Sentinel lymph node biopsy (SLNB) is a selective procedure that allows selective staging of the axilla with few side effects. However, indications for SLNB are not precisely defined yet, so some patients may be understaged and the axillary relapse rate may increase. This study was conducted to help clinicians assess the risk of ANI and analyzed six clinical and histological parameters to optimally recognize patients who might benefit from SLNB, with a minimal risk of false-negative rate. We retrospectively analyzed the ANI risk among 893 women treated by conservative surgery and radiation for T0, T1, or T2 invasive tumours < 3 cm in size. All patients underwent AD with sampling of a minimum of seven lymph nodes. In each case, we assessed the clinical and pathological tumor size, histological subtype (including grading), tumor location, age at diagnosis, and breast size. The global ANI rate in the entire cohort was 25.3%. In multivariate analysis, three variables were significantly predictive of the ANI risk: tumor size (P < 0.0001), histological subtype (P = 0.0005), and breast size (P = 0.004). By combining these parameters, we were able to define three categories of women with low (< 20%), intermediate (21%-25%), and high (> 25%) ANI risk. We suggest that women with nonpalpable (T0), T1 grade 1/2, and T2 < 3 cm tumors of medullary, mucinous, tubular, or papillary histological subtype are the best candidates for SLNB. For other patients with a higher ANI risk tumor, AD may still remain the best procedure to obtain accurate staging and definitive local control.
Adult↗
[Erysipelas: microbiological and pathogenic data].
Streptococcus pyogenes is considered as the primary cause of erysipelas and the virulence factors of this species are reviewed. The role of Staphylococcus aureus alone or associated with Streptococcus pyogenes remains unclear. Other etiologies are infrequent. Several techniques were used to detect bacteria (direct examination, culture, antigen or genome assay) in local samples (needle aspiration, swab.), in others sites (throat, blood cultures), or specific antibodies. The performance of the various diagnosis methods is evaluated. Despite the combination of 2 or more methods, the etiology remains unknown in almost 20 p. 100 of the cases.
Erysipelas↗