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Biomedical subjects

C Martin

Publications and source records attributed to C Martin.

At least 91 records · Page 5Linked to original sources

A phase I/II study of oral uracil/tegafur (UFT), leucovorin and irinotecan in patients with advanced colorectal cancer.

BACKGROUND: The aim of this study was to determine the maximum tolerated dose (MTD), toxicity profile and response rate of the oral 5-fluorouracil prodrug UFT (tegafur/uracil) and leucovorin (LV) in combination with irinotecan in patients with advanced or metastatic colorectal cancer. PATIENTS AND METHODS: Patients with histologically proven advanced or metastatic colorectal adenocarcinoma received first-line chemotherapy comprising UFT 250 mg/m(2)/day and LV 90 mg/day given on days 1 to 14, with escalating doses of irinotecan (200-300 mg/m(2)) administered intravenously on day 1 of a three-weekly cycle. Eligibility criteria were standard. The MTD was defined as the dose at which >33% of six patients experienced a dose-limiting toxicity (DLT) during cycle 1. RESULTS: A total of 32 patients were studied. Initially, six patients were treated at each of the irinotecan dose levels (200, 250 and 300 mg/m(2)) combined with UFT 250 mg/m(2)/day and LV 90 mg/day. DLTs consisting of grade 3 or 4 diarrhoea and febrile neutropenia were observed in one of 20 patients at 250 mg/m(2) and three of six patients at the 300 mg/m(2) irinotecan dose level. Having defined the MTD, the 250 mg/m(2) dose level was established as the recommended dose (RD) and expanded to 20 patients in whom treatment was generally well tolerated. The overall response rate was 19%, with five patients having a partial response (PR) and 18 stable disease (SD) out of 32 response-evaluable patients. CONCLUSION: UFT and LV can be safely combined with irinotecan. The RDs for future studies are UFT 250 mg/m(2)/day and LV 90 mg/day given on days 1-14, with irinotecan 250 mg/m(2) administered on day 1, every 3 weeks. This combination is well tolerated and active. Further investigation of UFT and LV in combination with irinotecan is warranted in patients with colorectal cancer.

Adenocarcinoma↗

Tea consumption, apoptosis, and colorectal adenomas.

Induction of apoptosis has been suggested as a mechanism for the anti-carcinogenic effect of tea constituents in animals and in vitro studies. We addressed this hypothesis in a human study. Study participants were consecutive patients who underwent colonoscopy at the UNC Hospitals (August 1998 to March 2000). Biopsies were taken from normal rectal mucosa. Apoptosis was scored by the terminal deoxyribonucleotide transferase-mediated digoxigenin dUTP nick end labeling (TUNEL) method and by standard morphological criteria. The analysis included 171 patients with adenomas (cases) and 323 adenoma-free controls. After adjusting for sex, age, race, and BMI, apoptotic score was inversely associated with adenoma: the odds ratios (ORs) for linear trend associated with tertiles were 0.3 (0.3-0.5) for morphologic score and 0.5 (0.4-0.6) for the TUNEL score, respectively. Tea consumption (2-3 and >3 versus <2 servings/day) showed a weak negative association with adenoma: the ORs were 0.7 (0.3-1.4) and 0.5 (0.2-1.1), respectively. Neither measurement of apoptotic score changed by the level of tea consumption (P value for Kruskal-Wallis test > or =0.5). We did not find statistical interaction between apoptotic score and tea consumption. Tea exposure is not associated with apoptosis in normal rectal tissue in vivo.

Adenoma↗

p16INK4A as a marker for cervical dyskaryosis: CIN and cGIN in cervical biopsies and ThinPrep smears.

AIM: To examine the potential of p16(INK4A) as a biomarker for dysplastic squamous and glandular cells of the cervix in tissue sections and ThinPrep smears. METHODS: Immunocytochemical analysis of p16(INK4A) expression was performed on 22 normal cervical tissue samples, five cervical glandular intraepithelial neoplasia (cGIN), 38 cervical intraepithelial neoplasia 1 (CIN1), 33 CIN2, 46 CIN3, and 10 invasive cancer cases (eight squamous and two adenocarcinomas). All samples were formalin fixed and paraffin wax embedded, and immunohistochemical analysis was carried out using a mouse monoclonal anti-p16(INK4A) antibody after antigen unmasking. The staining intensity was assessed using a 0 to 3 scoring system. In addition, the expression status of p16(INK4A) was examined in 12 normal ThinPrep smears, one smear exhibiting cGIN, and a total of 20 smears exhibiting mild, moderate, and severe dyskaryosis. Human papillomavirus (HPV) detection was carried out using a modified SYBR green assay system. Fluorogenic polymerase chain reaction (PCR) and solution phase PCR were used for specific HPV typing. RESULTS: p16(INK4A) immunoreactivity was absent in all normal cervical tissues examined. Dysplastic squamous and glandular cells were positive for p16(INK4A) expression in all cases included in this study, except for one CIN3 case. p16(INK4A) expression was mainly nuclear in CIN1 cases, and both nuclear and cytoplasmic in CIN2, CIN3, cGIN, and invasive cases. All cases positive for HPV expressed the p16(INK4A) protein, although not all cases found positive for p16(INK4A) were HPV positive. In general, the p16(INK4A) staining intensity was lower in cases negative for HPV or those containing a low risk HPV type. CONCLUSION: This pattern of overexpression demonstrates the potential use of p16(INK4A) as a diagnostic marker for cervical squamous and also glandular neoplastic lesions. In addition, the technique can be used to identify individual dyskaryotic cells in ThinPrep smears. Thus, p16(INK4A) is a useful marker of cervical dyskaryosis.

Biomarkers↗

Ceftriaxone (1 g intravenously) penetration into abdominal tissues when administered as antibiotic prophylaxis during nephrectomy.

A pharmacokinetics study was conducted to determine the effects of ceftriaxone administered before nephrectomy on the occurrence of postoperative wound infection. Ceftriaxone was administered as antibiotic prophylaxis in 11 consecutive patients undergoing nephrectomy who received 1,000 mg intravenously 30 min before surgery. Simultaneous blood and tissue samples were collected at three stages of the surgical procedure: opening of the abdominal cavity, nephrectomy, and closure of the abdominal cavity. Samples of following tissues were assayed: abdominal-wall fat, perirenal fat, kidney cortex and medulla, and urine. During the different stages of surgical procedures, ceftriaxone concentrations remained higher than the MIC90 of the potential pathogens (Staphylococcus aureus, Escherichia coli, and Enterobacteriaceae). In selected patients undergoing nephrectomy and requiring antimicrobial prophylaxis such as malnourished, debilitated, diabetic or immunosuppressed patients, the use of a single dose of ceftriaxone (1,000 mg) makes it possible to offer an optimal bacterial coverage for the prevention of postoperative infection. According to our kinetic evaluation, ceftriaxone is potentially a good antibiotic for prophylaxis in urological surgery.

Abdomen↗

The early allergic response in small airways of human precision-cut lung slices.

To study the role of small airways in the early allergic response (EAR), the method of human precision-cut lung slices (PCLS) was developed and used to examine the bronchoconstriction elicited by passive sensitisation and allergen provocation. Viable human PCLS of 250-microm thickness containing airways <1.5 mm in outer diameter were prepared from lung lobes obtained from lung resection and taken into culture. According to the low release of lactate dehydrogenase and the constant ciliary beat frequency, human PCLS were viable for at least 3 days. Following overnight passive sensitisation with serum from allergic individuals, administration of grass-pollen extract or activating immunoglobulin E antibody resulted in immediate airway contraction that was quantified by videomicroscopy. The extent of the EAR increased with decreasing airway size (outer airway diameter), with the strongest response occurring in the terminal bronchioles. Histamine receptor antagonism was ineffective, and leukotriene or thromboxane receptor antagonism attenuated the early allergic response only in some cases. However, simultaneous blockade of leukotriene and thromboxane receptors almost completely prevented the early allergic response in the precision-cut lung slices from all individuals, suggesting such a dual treatment as a potential future asthma therapy.

Acetates↗

[Paraneoplastic opsoclonus-myoclonus syndrome associated with small-cell lung cancer].

Opsoclonus-myoclonus syndrome was observed in a patient treated for small-cell lung cancer. Opsoclonus presented as anarchic involuntary eye movements associated with myoclonies of the limbs and trunk. Opsoclonus-myoclonus is exceptional and a specific expression among several paraneoplastic manifestations described in small-cell lung cancer. These manifestations develop late after diagnosis of cancer. Presence of anti-neuronal antibodies in the serum (inconstant) is a factor of very poor prognosis.

Aged↗

[Advantage of virtual endoscopy in the evaluation of the ossicular chain].

PURPOSE: Our study consists of a comparison of traditional computed tomography (CT) data sets with 2 views of virtual endoscopy in the preoperative evaluation of various diseases of the middle ear. MATERIALS AND METHODS: We studied 59 patients, all sent for conductive hearing loss with normal eardrum who underwent a complete CT examination: axial helical acquisition and coronal incremental acquisition: virtual endoscopy with selection of two reproducible views: an external one of the auditory canal and a lower one of the hypotympanum. Reading was performed by 2 independent radiologists. All patients were subsequently operated by the same surgeon. Results were compared with surgical reports. RESULT: Virtual endoscopy is valuable for the evaluation of ossicular and prosthesis dislocations, morphological anomalies of the malleus, incus, and stapes superstructure. Nevertheless, standard axial and coronal CT images remain necessary as confirmed by the poor results of virtual endoscopy in cases of attic obstruction, cholesteatomas and otospongiosis. CONCLUSION: Virtual endoscopy is a valuable technique of the evaluation of some ossicular chain pathologies but it cannot be used alone.

Adolescent↗

Ultrasharp magnetization steps in perovskite manganites.

We report a detailed study of steplike metamagnetic transitions in polycrystalline Pr0.5Ca0.5Mn0.95Co0.05O3. The steps have a sudden onset below a critical temperature, are extremely sharp (width <2x10(-4) T), and occur at critical fields which are linearly dependent on the absolute value of the cooling field in which the sample is prepared. Similar transitions are also observed at low temperature in non-Co doped manganites, including single crystal samples. These data show that the steps are an intrinsic property, qualitatively different from either previously observed higher temperature metamagnetic transitions in the manganites or metamagnetic transitions observed in other materials.

Journal Article↗

Microphase separation in Pr0.67Ca0.33MnO3 by small-angle neutron scattering.

We have evidenced by small-angle neutron scattering at low temperature the coexistence of ferromagnetism (F) and antiferromagnetism (AF) in Pr0.67Ca0.33MnO3. The results are compared to those obtained in Pr0.80Ca0.20MnO3 and Pr0.63Ca0.37MnO3, which are F and AF, respectively. Quantitative analysis shows that the small-angle scattering is not due to a mesoscopic mixing but to a nanoscopic electronic and magnetic "red cabbage" structure, in which the ferromagnetic phase exists in the form of thin layers in the AF matrix (stripes or 2D "sheets").

Journal Article↗

Optical pulsations from the anomalous X-ray pulsar 4U0142+61.

Anomalous X-ray pulsars (AXPs) differ from ordinary radio pulsars in that their X-ray luminosity is orders of magnitude greater than their rate of rotational energy loss, and so they require an additional energy source. One possibility is that AXPs are highly magnetized neuron stars or 'magnetars' having surface magnetic fields greater than 10(14) G. This would make them similar to the soft gamma-ray repeaters (SGRs), but alternative models that do not require extreme magnetic fields also exist. An optical counterpart to the AXP 4U0142+61 was recently discovered, consistent with emission from a magnetar, but also from a magnetized hot white dwarf, or an accreting isolated neutron star. Here we report the detection of optical pulsations from 4U0142+61. The pulsed fraction of optical light (27 per cent) is five to ten times greater than that of soft X-rays, from which we conclude that 4U0142+61 is a magnetar. Although this establishes a direct relationship between AXPs and the soft gamma-ray repeaters, the evolutionary connection between AXPs, SGRs and radio pulsars remains controversial.

Journal Article↗

[Motives for the prescription of antibiotics in the emergency department of the University Hospital Center in Nice. A prospective study].

OBJECTIVES: Since April 1999, we have set-up an infectious disease consultation in the emergency unit of the University Hospital in Nice. Unjustified antiobiotherapy is often initiated. We therefore conducted a survey to study the motives and validity of antibiotic prescriptions. METHOD: This prospective study was conducted in two phases. The first consisted in asking the emergency physicians prescribing antibiotics to fill-in a questionnaire giving information on the diagnosis established and the antiobiotherapy proposed. In the second phase, the diagnoses and corresponding treatments were submitted to 4 experts who assessed the acceptability of the diagnoses and the antibiotics prescribed. The experts only had access to the clinical and para-clinical data available. Moreover, their therapeutic judgement was based on previously published consensuses. RESULTS: The 6-month survey collected 117 questionnaires that could be analysed. The rate of error in diagnosis was of 33% (39/117). Thoracic x-rays could not be interpreted in 11% of cases. In single variant analysis, factors of erroneous diagnosis were due to its interpretation by an internist, the diagnostic category of "broncho-pulmonary infections" and the lack of documentation. In multi variant analysis, only the lack of documentation was related to erroneous diagnosis (OR = 5.5; IC 95% (2.03; 15.30), p < 0.0002). The rate of antibiotherapy not adapted to the diagnosis made by the physician was of 32% (37/117). In 24 cases the modalities of the prescription were incorrect and in 13 cases the prescription was unjustified. Only the status of the prescriber (internist) was statistically associated with an antibiotherapy not adapted to the diagnosis (OR = 2.2; IC 95% (0.93; 5.26), p < 0.05). CONCLUSION: Unjustified antibiotherapy in an emergency unit is generally due to erroneous diagnosis of infection. The lack of documentation and inexperience of the prescribers appear to be the two elements contributing to unjustified antibiotherapy.

Anti-Bacterial Agents↗

The combination of a heat and moisture exchanger and a Booster: a clinical and bacteriological evaluation over 96 h.

OBJECTIVE: To determine whether the combination with a new device (Booster ) for active humidification improves the efficacy of a hydrophobic heat and moisture exchanger (HME). DESIGN AND SETTING: Prospective, interventional study in the ICU of a university hospital. PATIENTS: Consecutive patients requiring controlled mechanical ventilation INTERVENTIONS: Patients were ventilated with a HME, and a Booster was added for 96 h to the ventilatory circuit. MEASUREMENTS AND RESULTS: During the inspiration phase the following factors were measured: peak and mean airway pressures, maximal (beginning of inspiration), minimal (end of inspiration), and mean values of temperature of inspired gases, and relative and absolute humidity of inspired gases. Microbiological samples were obtained from the Booster, the ventilator side of the HME, and the tracheal secretions on days 1 and 4. Minimal and mean temperatures were increased as soon as the Booster was used and this increase was maintained for 96 h until the Booster was withdrawn. Then the temperature returned to baseline values. Absolute humidity values followed the same course. There was also some indirect evidence of very little, if any, changes in the HME resistance. The ventilatory side of the HMEs remained sterile in each patient, and the Booster was colonized by the same bacteria as those in the tracheal secretions. CONCLUSIONS: Adding the Booster to a hydrophobic HME improved the heat and water preservation of ventilatory gas.

Bacteria↗

A French study of the Dominic Interactive.

INTRODUCTION: The Dominic Interactive was developed in North America to assess a child's perception of her/his own symptoms, which is critical to balance parents' and school professionals' perception. It is a computerized, DSM-IV-based pictorial questionnaire akin to a video game, for children aged 6-11. A strengths and competencies scale displays positive situations. Most children complete the Dominic Interactive 90 situations within 10-15 min. OBJECTIVE: Because of the cultural differences between North American and French children, a study of the appropriateness of the instrument to assess French children was required. METHODS: The CD-ROM-based Dominic Interactive was completed by 253 community children, and by 150 children from outpatient clinics in four French cities. The latter also received clinical diagnoses. Prevalence estimates yielded by the Dominic Interactive in the general population and referred children, relationships between prevalence estimates based on the Dominic Interactive and clinical judgments, and differences between Dominic Interactive scores in sub-samples of children with and without a clinical diagnosis were studied. RESULTS: Significant differences between clinically referred and non-referred children were found for every diagnosis, and between Dominic Interactive scores of referred children with and without a clinical diagnosis with the exception of oppositional disorder. Parental acceptability of the instrument was never a problem, children like it, and clinicians' comments were positive. DISCUSSION: Reference and clinical judgment both indicate that the Dominic Interactive is appropriate to assess child mental health in France. Clinical judgment discrepancies between sites and small numbers are the limitations of this study. CONCLUSION: The instrument performed well in the French context. The potential advantages of using the Dominic Interactive (children enjoy the activity, parents approve of it, it is relatively cost-effective, etc.) suggest its applicability in other settings.

Child↗

High duplication of the internal jugular vein: clinical incidence in the adult and surgical consequences, a report of three clinical cases.

Duplication of the internal jugular vein (IJV) is a rare malformation. Three intraoperative cases are reported. In our personal experience, the clinical incidence of the anomaly is approximately 4 per 1,000 unilateral neck dissections. The venous duplication is at a variable height, affecting the superior part of the IJV. The lateral branch of the accessory nerve (XI) always passes medially to the anterior vein and laterally to the posterior vein, between the venous duplication. This is most often unilateral but sometimes bilateral. The IJV may be normal, dilated or ectatic. The discovery of this anatomical variation has practical implications during cervical lymph node clearance, either functional or radical, during oncological surgery necessitating viewing the IJV and its affluents and the lateral branch of the accessory nerve. The embryological explanation suggests a topographical "conflict" between the development of the IJV and the lateral branch of the accessory nerve. The French version of this article is available in the form of electronic supplementary material and can be obtained by using the Springer LINK server located at http://dx.doi.org/10.1007/s00276-002-0020-y.

Aged↗