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Biomedical subjects

C Martin

Publications and source records attributed to C Martin.

At least 55 records · Page 3Linked to original sources

Sequential mitoxantrone/prednisone followed by docetaxel/estramustine in patients with hormone refractory metastatic prostate cancer: results of a phase II study.

BACKGROUND: Mitoxantrone/prednisone ameliorates symptoms in hormone refractory prostate cancer (HRPC) but has no effect on survival. Docetaxel (Taxotere)/estramustine improves response but with significant toxicity. We reasoned that a sequential administration of the two regimens could be a viable alternative for delivering full doses of chemotherapy, avoiding overlapping toxicity and preserving dose intensity. PATIENTS AND METHODS: Thirty HRPC patients were treated with mitoxantrone 10 mg/m(2), day 1, every 3 weeks, plus prednisone 5 mg twice daily, for three cycles, followed by estramustine phosphate, 280 mg three times daily, days 1 to 5, plus docetaxel 75 mg/m(2), day 2, every 3 weeks for a maximum of 10 cycles. RESULTS: All patients were assessable for response and toxicity. After mitoxantrone/prednisone treatment, the prostate-specific antigen (PSA) response rate was 23%, which increased to 63% after completion of sequential mitoxantrone/prednisone and docetaxel/estramustine treatment (12 partial and 7 complete responses). With a median follow-up of 18 months, median survival for all patients was 18 months, and median progression-free survival was 10 months. The mitoxantrone/prednisone regimen was well tolerated, and the only grade 3-4 toxicity was grade 3 neutropenia in four (13%) patients. Twenty-nine patients received a total of 173 cycles of docetaxel/estramustine (median, 6 cycles/patient). Six (20%) patients had grade 3-4 neutropenia and two (6%) patients had febrile neutropenia episodes. The most frequent non-hematological toxic effects were asthenia, nausea and vomiting, edemas and onycholysis. Two (6%) patients had deep venous thrombosis. CONCLUSIONS: Mitoxantrone/prednisone followed by docetaxel/estramustine is a well-tolerated and active regimen in HRPC. Sequential therapy is feasible and can be used to integrate novel, more active regimens.

Aged↗

[Selective digestive decontamination: the light as changed from red to green].

OBJECTIVES: To study the efficacy of selective digestive decontamination (SDD) for the prevention of nosocomial infections, particularly pneumonia, as well as its impact on the emergence of multiresistant bacteria. DATA SOURCES: Data collected from the Pubmed: original articles, review articles and editorial published on SDD. The keywords were: selective digestive decontamination, pneumonia, intensive care unit, infection. DATA SELECTION: Ten randomized clinical trials performed since 1995 in mechanically ventilated adult patients hospitalized in intensive care unit. RESULTS: The rationale for the use of SDD consists on the parenteral administration of a short course of antibiotic associated with the topical use of non-absorbable antibiotics directed against Gram negative bacteria. Five randomized studies described a reduction in the incidence of pneumonia associated with SDD. Only one study has showed a decrease in mortality rate. The other five studies, which present some methodological limitations, concluded the lack of efficacy of SDD. Regarding the emergence of multiresistant bacteria, the literature underlines the role of environment. The use of SDD seems to trigger the resistance in endemic areas, while these are softened in the units with a good control of their ecology. CONCLUSION: The data from the literature provide arguments to use SDD in targeted patient populations like multiple traumas in intensive care units, which have a low rate of multiresistant bacteria.

Anti-Bacterial Agents↗

[Salmonella of Indian origin: pseudo-susceptibility to fluoroquinolones].

We report the case of a patient presenting with typhoid fever after returning from a stay in India. This infection was not cured with a course of ciprofloxacin, due to a reduced susceptibility of the bacteria to the drug. This decreased susceptibility to fluoroquinolones was not detected by the antibiogram, but the MIC for nalidixic acid was greater than 32 mg/l. This case suggests using a third generation cephalosporin instead of a quinolone, for people coming from a high-risk zone. It also suggests that the MIC for nalidixic acid and for norfloxacin can be used as the first clue for a reduced susceptibility to fluoroquinolones.

Adult↗

[Anatomic study and advantages of the free rectus abdominis flap for head and neck reconstruction].

INTRODUCTION: The main goal of using the free flap is to be able to carry out extensive surgical resection resulting in good functional outcome. The aims of this study were to define the best area for free rectus abdominis harvest and to assess its value in head and neck reconstruction. MATERIAL AND METHODS: Twenty rectus abdominis flaps were studied in ten fresh cadavers. A review of the literature of the free rectus abdominis flap in head and neck reconstruction yielded the main recipient sites and complications (flap necrosis and postoperative abdominal hernia). A reconstruction was performed after near total glossectomy. RESULTS: With seven perforators and four cutaneous branches of intercostal nerves, the paraumbilical region is the best area to harvest this flap. The rectus abdominis free flap seems to be adapted for near total glossectomy reconstruction. Previous studies reported that this flap was essentially used for oropharynx and skull base reconstruction. The main complications are flap necrosis (4%) and abdominal hernia (3%). CONCLUSION: The paraumbilical rectus abdominis free flap is reliable and easy to use with a two-team approach in head and neck reconstruction with moderate donor site morbidity. It is useful for reconstruction of large defects of the oropharynx and skull base. Sensory-motor reinnervation superiority for deglutition in tongue reconstruction still needs to be evaluated.

Cadaver↗

Blood-feeding in the young adult filarial worms Litomosoides sigmodontis.

In this study with the filarial model Litomosoides sigmodontis, we demonstrate that the worms ingest host red blood cells at a precise moment of their life-cycle, immediately after the fourth moult. The red blood cells (RBC) were identified microscopically in live worms immobilized in PBS at 4 degrees C, and their density assessed. Two hosts were used: Mongolian gerbils, where microfilaraemia is high, and susceptible BALB/c mice with lower microfilaraemia. Gerbils were studied at 12 time-points, between day 9 post-inoculation (the worms were young 4th stage larvae) and day 330 p.i. (worms were old adults). Only the very young adult filarial worms had red blood cells in their gut. Haematophagy was observed between days 25 and 56 p.i. and peaked between day 28 and day 30 p.i. in female worms. In males, haematophagy was less frequent and intense. Similar kinetics of haematophagy were found in BALB/c mice, but frequency and intensity tended to be lower. Haematophagy seems useful to optimize adult maturation. These observations suggest that haematophagy is an important step in the life-cycle of L. sigmodontis. This hitherto undescribed phenomenon might be characteristic of other filarial species including human parasites.

Age Factors↗

Interaction between two quantitative trait loci affects fetal haemoglobin expression.

The biological mechanisms controlling complex quantitative traits are likely to be affected by interactions between genetic factors, sometimes referred to as epistasis. The identification of interacting loci through genetic analyse faces many challenges, and few examples of replicated findings of interaction exist for humans and model system organisms. The replication of an interaction, or the non-independence, of two quantitative trait loci (QTL) affecting the developmental switch from the expression of fetal to adult haemoglobin is reported here. Fetal haemoglobin expression in adults is a highly heritable, yet complex, phenotype. Using a sample of 874 dizygotic twin pairs of European descent, we found linkage to a QTL on chromosome 8 to be conditional on the twin pairs' genotypes at a polymorphism in the beta-globin complex; an interaction originally identified in a large Asian Indian kindred. The beta-globin polymorphism has been previously shown to be associated with fetal haemoglobin levels in adults. This study reports the first known replication of a genetic interaction between QTLs influencing a complex human trait.

Chromosomes, Human, Pair 8↗

Adolescent medicine in paediatric practice.

Adolescents are a growing area in paediatric practice in both hospital and community settings. They make up around one quarter of the practice of many paediatricians. Yet until recently there has been little formal interest in young people's health in the UK. The situation is now changing, particularly following the publication of the "National Service Framework for children, young people and maternity services", which places a major emphasis on adolescent health. Given that this area is relatively new to many paediatricians, this article aims to provide an overview of the range of health problems that affect young people, to provide practical advice for working with this group in paediatric practice, and to outline current and future opportunities for training in adolescent health in the UK.

Adolescent↗

Molecular pathology of prostate cancer.

The molecular pathology of prostate cancer is complex; not only are multiple genes involved in its pathogenesis, but additional environmental factors such as diet and inflammation are also involved. The exhaustive research into prostate cancer to date has demonstrated a complex interaction of multiple genes and environmental factors, some of which may be more important in individual prostate cancer cases. This is an exciting era, with the emergence of new investigative tools such as DNA microarray technology and the application of the field of proteomics to the study of human cancers. Knowledge of genetic changes underlying the initiation, development, and progression of prostate cancer is accumulating rapidly. With increasing knowledge, it may be possible to distinguish indolent from aggressive prostate tumours by molecular fingerprinting. This review discusses the most consistently reported molecular pathological findings in hereditary and sporadic prostate cancer, together with new concepts and technologies.

Chromosome Aberrations↗

Integrating the Modelling of EN 1828 and Galen CCAM Ontologies with Protégé: towards a Knowledge Acquisition Tool for Surgical Procedures.

The presentation assess the usability of the ontology platform protégé integrated with the terminology reasoning tool RACER to represent different terminology systems as the CEN European standard EN 1828 which is a categorical structure and the extensive French coding system CCAM supported by a GALEN representation. We present the 2 systems and some results showing the easiness to test the consistence of the ontology or of instances of terminology systems.This type of software tool which is accessible as open source could support a convergent "reference terminology representation" approach. Based on a formal representation development and allowing diversity in linguistic expressiveness of end users this approach can associate shared knowledge acquisition in the public domain and competing systems, software developers and researchers.

Humans↗

Target concentrations of remifentanil with propofol to blunt coughing during intubation, cuff inflation, and tracheal suctioning.

BACKGROUND: The target blood concentrations of propofol and remifentanil, when used in combination, required to blunt the cough response to tracheal intubation, cuff inflation, and tracheal suctioning without neuromuscular blocking agents are not known. METHODS: In a randomized prospective study, 81 patients were enrolled to determine which of three target remifentanil blood concentrations was required to blunt coughing during intubation, cuff inflation, and tracheal suctioning. Anaesthesia was achieved with propofol at a steady effect-site concentration of 3.5 microg ml(-1). The target blood remifentanil concentrations were 5, 10, or 15 ng ml(-1). These concentrations were maintained for 12 min before intubation. RESULTS: There was no cough response to intubation in more than 74% of patients and no significant difference in the incidence of coughing with intubation between the three groups. Significant difference in coughing, diminishing with increasing remifentanil target concentration, was observed with cuff inflation (P=0.04) and tracheal suctioning (P=0.007). Bradycardia and hypotension was more frequent with the remifentanil target concentration of 15 ng ml(-1). Tracheal suctioning resulted in more coughing than intubation (P=0.01) or cuff inflation (P=0.004). CONCLUSION: Target remifentanil blood concentrations of 5, 10, and 15 ng ml(-1) associated with a 3.5 microg ml(-1) propofol target blood concentration provided good intubating conditions and absence of cough about 75% of the time. Higher target remifentanil concentrations were associated with less coughing during tracheal tube cuff inflation and tracheal suctioning.

Adolescent↗

Pressor responses to platelet-activating factor and thromboxane are mediated by Rho-kinase.

Platelet-activating factor (PAF) contracts smooth muscle of airways and vessels primarily via release of thromboxane. Contraction of smooth muscle is thought to be mediated either by calcium and inositol trisphosphate (IP(3))-dependent activation of the myosin light chain kinase or, alternatively, via the recently discovered Rho-kinase pathway. Here we investigated the contribution of these two pathways to PAF and thromboxane receptor-mediated broncho- and vasoconstriction in two different rat models: the isolated perfused lung (IPL) and precision-cut lung slices. Inhibition of the IP(3) receptor (1-10 microM xestospongin C) or inhibition of phosphatidylinositol-specific PLC (30 microM L-108) did not affect bronchoconstriction but attenuated the sustained vasoconstriction by PAF. Inhibition of myosin light chain kinase (35 microM ML-7) or of calmodulin kinase kinase (26 microM STO609), which regulates the phosphorylation of the myosin light chain, had only a small effect on PAF- or thromboxane-induced pressor responses. Similarly, calmidazolium (10 microM), which inhibits calmodulin-dependent proteins, only weakly reduced the airway responses. In contrast, Y-27632 (10 microM), a Rho-kinase inhibitor, attenuated the thromboxane release triggered by PAF and provided partial or complete inhibition against PAF- and thromboxane-induced pressor responses, respectively. Together, our data indicate that PAF- and thus thromboxane receptor-mediated smooth muscle contraction depends largely on the Rho-kinase pathway.

Amides↗

Phase II study of ecteinascidin-743 in advanced pretreated soft tissue sarcoma patients.

PURPOSE: A multicenter phase II study evaluating efficacy, safety, and pharmacokinetics of ecteinascidin-743 (ET-743) in pretreated advanced soft tissue sarcoma patients. PATIENTS AND METHODS: Patients received ET-743 1,500 microg/m(2) (24-hour intravenous infusion) every 3 weeks (group 1, 26 patients with one to two prior single agents or one previous combination chemotherapy; group 2, 28 patients with three or more prior single agents or two or more previous combination chemotherapies). Results Patients (30 women, 24 men) had a median age of 48 years (range, 22 to 71 years); 41% had leiomyosarcoma (eight of 22 of uterine origin), a median of two involved organs (range, one to four), and 93% had documented progressive disease at study entry. Patients received a median of three cycles (range, one to 20); 28% received six or more cycles. Fifty-two patients were assessable for response (WHO criteria): two partial responses, four minor responses, and nine with stable disease (> or = 6 months). Three patients were rendered tumor free after surgery. Median progression-free survival was 1.9 months (range, 0.69 to 17.90 months); 24% of patients were progression free at 6 months. Median survival was 12.8 months, with 30% of patients alive at 2 years. Four patients withdrew because of treatment-related toxicity. Two treatment-related deaths occurred (renal failure and febrile neutropenia, and rhabdomyolysis and decompensated cirrhosis, respectively) that were probably related to protocol eligibility violations. Reversible grade 3 to 4 AST or ALT occurred in 50% of patients and grade 3 to 4 neutropenia occurred in 61% of patients, with six episodes of febrile neutropenia. Nausea, vomiting, and asthenia were prevalent but mild and manageable. CONCLUSION: With a 4% overall response rate (95% CI, 0.5 to 12.8) and an 11% rate of third-party-verified tumor regression (overall response rate + minor response), ET-743 has a 24% 6-month disease progression control rate, confirming evidence of antitumoral activity and a manageable safety profile in patients experiencing disease progression with pretreated soft tissue sarcoma.

Adult↗

[Long-term treatment of phantom- and stump pain with Botulinum toxin type A over 12 months. A first clinical observation].

Recently we were able to describe the successful treatment of phantom pain and stump pain with botulinum toxin A in a first pilot study. This case report over a 1-year period now demonstrates that long-term treatment for this indication is possible. We injected 4 x 25 IU of botulinum toxin A (Botox) into trigger points of the stump muscles of a lower limb amputee who suffered from severe phantom and stump pain. With four injections performed every 3 months, the patient became almost completely pain-free, and his intrathecal morphine therapy could be reduced to 40% of the initial dose. Intrathecal clonidine was eliminated completely, as were the oral analgesics. A surgical treatment suggested for the stump pain was no longer necessary, and we suppose that botulinum toxin can also improve the tolerance of artificial limbs in cases of stump pain.

Amputation, Surgical↗

[Indications and limits of recombinant human erythropoietin in intensive care unit].

OBJECTIVE: To analyze the data from the literature on erythropoietin and the future indications of recombinant human erythropoietin in intensive care unit (ICU) patients. DATA SOURCE: References were obtained from computerized bibliographic research (Pubmed) from 1986 to 2003, except for some physiologic data. DATA SELECTION: Original articles, reviews, and letters to editor in French and English were selected and analyzed. DATA SYNTHESIS: An anemia is often observed in patients hospitalized in ICU. This anemia may be due to many reasons. The management of anemia consists on the treatment of the underlying disease associated with the transfusion of red blood cells. Recent studies provided evidence of an association between transfusions and mortality in ICU patients. The anemia of ICU patients is compared to the anemia of chronic diseases, which is characterized by a blunted erythropoietin. A treatment with rHuEPO may be a future therapeutic of the anemia in such patients. A multicentric study shows the efficacy of recombinant erythropoietin therapy on a decrease in the use of red blood cell, and another clinical trial highlights a decrease of the proportion of ICU patients receiving red blood cell. Recombinant erythropoietin could be an alternative to transfusion in certain conditions and certain ICU patients. Further studies are needed to determine the consequences on mortality rate and to clarify the place of this therapy in ICU patients.

Anemia↗