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Biomedical subjects

C Martin

Publications and source records attributed to C Martin.

At least 235 records · Page 13Linked to original sources

[Glycopeptides].

OBJECTIVES: To review pharmacology, pharmacokinetic and therapeutic use of glycopeptides in intensive care units. DATA SOURCES: Extraction from Medline database of French and English articles on glycopeptides and search along with major review articles. DATA SELECTION: The collected articles were reviewed and selected according to their quality and originality. The more recent data were selected. DATA SYNTHESIS: Glycopeptides are bactericidal antibiotics which are only active against Gram positive species acting by inhibiting peptidoglycan synthesis. They had been in clinical use for almost 30 years without high-level resistance underlining. For ten years, there have been disturbing reports of first, resistance to vancomycin in enterococcal species and more recently in strains of Staphylococcus aureus by complex and large mechanisms of action. This new resistances may lead to a therapeutic impasse and a fatal issue for infected patients. The only response to this situation is the respect of prescription rules and the careful use of antibiotics. CONCLUSION: Considering their spectrum, glycopeptides are an antibiotic family which importance is fundamental to treat infected patients of intensive care units. Staff members of intensive care units are responsible for their good use.

Anti-Bacterial Agents↗

Differences in young adult psychopathology among drug abstainers, experimenters, and frequent users.

Shedler and Block offered the provocative proposal that individuals who experiment with drugs are psychologically healthier than either those who abstain completely or those who are frequent users. Not all studies have come to such conclusions, however. In an effort to specify under what conditions Shedler and Block's conclusions might hold, the present study examined three groups of drug users (abstainers, experimenters, frequent users) classified according to three different criteria: (a) marijuana use at age 20; (b) alcohol use during 10th grade; and (c) alcohol use at age 20. The three groups were compared at age 20 in terms of personality, deviant behavior, and psychopathology. The results revealed that abstainers were never more psychologically impaired, and were occasionally healthier, than experimenters. Frequent users of marijuana were consistently more imparied than both the abstainers and experimenters, in terms of both internalizing and externalizing disorders. Classification according to marijuana use appeared to be more related to psychopathology than did classification according to alcohol use.

Adolescent↗

Effects of global regulatory proteins and environmental conditions on fimbrial gene expression of F165(1) and F165(2) produced by Escherichia coli causing septicaemia in pigs.

Escherichia coli O115:F165 strains are associated with septicaemia in young pigs and possess at least two types of fimbriae. F165(1) fimbriae belong to the P fimbrial family and F165(2) fimbriae belong to the S fimbrial family. Regulatory regions of foo (F165(1)) and fot (F165(2)) fimbrial gene clusters from wild-type strain 4787 were sequenced and characterised. Expression of F165(1) and F165(2) fimbrial genes was analysed by using lacZ and/or luxAB as reporter genes under the control of the native fimbrial promoters. Differential expression of fimbrial genes was observed. Global regulatory mechanisms such as catabolite repression, leucine-responsive regulatory protein (Lrp), methylation and DNA supercoiling were demonstrated to influence foo and fot expression. foo and fot expression was optimal at 37 degrees C and under aerobic conditions. Expression of foo was higher on minimal medium, whereas fot expression was higher on complex Luria-Bertani medium. This could reflect an in vivo differential expression.

Amino Acid Sequence↗

9:15-9:30. Use of a Spherical 3-D Blob Analysis Program as a Method of Determination of Standardized Uptake Value (SUV) for Following Tumor Response to Chemotherapeutic Agents (CTA).

Malignant tumors exhibit increased glucose metabolism which can be quantitated by SUV. SUV is criticized for its variability resulting from many factors including the method of drawing region of interest (ROI) over the tumor. The most common method manually draws or places ROI on various slices displaying highest FDG activity. This time consuming method is associated with significant individual variation. We describe a more reproducible, efficient spherical 3-D blob analysis method of SUV and tumor volume (TV) determination to evaluate CTA response. The spherical 3-D Blob analysis program is a completely automated method with data processing performed using IDL (RS Inc., Colorado). A threshold value is set for the ROI; all voxels above threshold are grouped by connectivity. Grouped voxels, called "blobs", are displayed and statistics are calculated for each group. The threshold set for blob extraction and SUV determination is usually three times above background and is constant on repeat scans. Eight patients with metastatic carcinoma underwent PET/CT/MRI prior to and one week after chemotherapy. Three patients also had scans at one month. Maximum and average SUV's and TV were determined and appeared to be very reproducible when there was no clinical response or change on CT/MR. In these patients, repeat SUV's and volumes of the lesions (n = 38) varied by less than 20% of baseline. An increase/decrease in maximum SUV or TV correlated with a similar change in lesion size on CT/MR. The average SUV did not change. The spherical 3-D blob analysis program appears to be a reliable, efficient method of determining maximum SUV and volumetric measurements for following tumor response to CTA.

Journal Article↗

Parasitology and immunology of mice vaccinated with irradiated Litomosoides sigmodontis larvae.

This study was performed with Litomosoides sigmodontis, the only filarial species which can develop from the infective larvae to the patent phase in immunocompetent laboratory BALB/c mice. Parasitological features and immune responses were analysed up to 3 months before and after challenge inoculation, by comparing 4 groups of mice: vaccinated challenged, challenged only, vaccinated only, and naive mice. Male larvae were very susceptible to irradiation and only female irradiated larvae survived in vivo. Protection, assessed by a lower recovery rate, was confirmed and was established within the first 2 days of challenge. This early reduction of the recovery rate in vaccinated challenged mice was determined by their immune status prior to the challenge inoculation. This was characterized by high specific IgM and IgG subclass (IgG1, IgG2a and IgG3) levels, high specific IL-5 secretion from spleen cells in vitro and a high density of eosinophils in the subcutaneous connective tissue. Six h after the challenge inoculation, most tissue eosinophils were degranulated in vaccinated challenged mice. Thus, in the protocol of vaccination described, protection appeared mainly to result from the stimulation of a Th2 type response and eosinophils seemed to be the main effectors for the increased killing of infective larvae in vaccinated challenged mice. Two months after challenge inoculation, the percentage of microfilaraemic mice was lower in vaccinated challenged mice as a consequence of this overall reduction in the worm load. In both vaccinated challenged and challenged only groups, the in vitro splenocyte proliferative capacity was reduced in microfilaraemic mice.

Animals↗

Cytotoxic effects of topotecan combined with various active G2/M-phase anticancer drugs in human tumor-derived cell lines.

Topotecan (TPT) is a DNA-Topoisomerase I poison that exhibits antitumor activity. TPT, like other DNA-damaging agents, arrests or delays cell cycle progression during S- and G2-phase in a wide variety of tumor-derived cell lines. Particularly, the G2-arrest gives time for the cell to repair its DNA lesions prior to starting a new cell cycle. Based on these observations, we assessed the interaction between TPT and G2/M-active agents in p53-mutated cell lines of diverse origin in order to achieve cell toxicity. Two short-term sequential schedules were administered (TPT --> G2/M-active drug at the interval of greatest TPT-induced G2/M-phase cell arrest, and G2/M-active drug --> TPT), in three human tumor-derived cell lines with proven sensitivity to the following drugs: Bleomycin in HEp-2 (squamous larynx carcinoma); Docetaxel in SKBr-3 (breast adenocarcinoma); Etoposide in NCI-H23 (non-small-cell lung cancer). Our results show that: 1) Sequential TPT --> G2/M-active drugs are synergistic when administration overlapped the maximum percentage of TPT-induced G2/M-phase cell arrest interval in all three mutated p53 cell lines; 2) the reverse sequential schedule (G2/M-active drug --> TPT) was antagonistic, and being only additive for Etoposide --> TPT association. In conclusion, our findings further support the potential cytotoxic role of TPT in combination with other active drugs when the correct schedule of administration is applied. In addition, they provide a rationale for new applications in clinical trials using short-term sequential TPT --> G2/M-active drugs.

Antibiotics, Antineoplastic↗

High-dose therapy with autologous stem-cell transplantation (ASCT) after first progression prolonged survival of follicular lymphoma patients included in the prospective GELF 86 protocol.

BACKGROUND: Among the 566 patients with follicular lymphomas (FL) included in the GELF 86 prospective trials from October 1986 to September 1995, 372 with progressive/relapsing disease were analyzed retrospectively to identify prognostic factors at first relapse. PATIENTS AND METHODS: For progressive FL, patients received mono- (22%) or polychemotherapy (78%) followed by high-dose therapy (HDT) with ASCT for 83 patients (22%). The median time to progression from initial treatment was 23 months (range 3-102 months) and 24% of documented patients (52 of 217) had histological transformation (HT). Salvage therapy produced an overall response in 64% of patients and the five-year survival from progression was 42%. RESULTS: For patients who underwent HDT with ASCT compared to standard treatment, five-year freedom from second failure was at 42% vs. 16% (P = 0.0001) and five-year survival was 58% vs. 38% (P = 0.0005), respectively. The benefit of HDT and ASCT remained if we consider only patients less than 65 years (five-year survival at 60% vs. 40%; P = 0.001). Multivariate analysis of parameters significant according to univariate analysis found that no ASCT at first progression, age at relapse > 50 years, progression on-therapy were adversely significant on survival. CONCLUSIONS: HDTwith ASCT compared to standard treatment prolonged remission and survival after first progression of FL patients.

Age Factors↗

A comparison of psychological functioning in women at different stages of in vitro fertilization treatment using the mean affect adjective check list.

PURPOSE: The objectives were to identify the stage/s of IVF treatment where a woman is most vulnerable to psychological stress, and to assess the Mean Affect Adjective Check List (MAACL) as a measure of psychological functioning during IVF treatment, which has hitherto not been reported. METHODS: Thirty-seven women undergoing IVF treatment according to the long protocol of controlled ovarian stimulation completed the MAACL questionnaire at the following stages: (a) before treatment (visit 1), (b) before embryo transfer (visit 2), and (c) before pregnancy test (visit 3). RESULTS: Apart from anxiety scores for visit 2, the hostility, depression, and state anxiety scores for visit 3 were higher than the corresponding scores for visits 1 and 2 (P < 0.001). Anxiety scores for visits 2 and 3 were similar. CONCLUSIONS: Psychological counseling should be targeted at women after embryo transfer and leading up to the pregnancy test. The MAACL is a useful method for measuring psychological stress in women during IVF treatment.

Age Factors↗

Effects of the thromboxane receptor agonist U46619 and endothelin-1 on large and small airways.

Recently attention has been drawn to the role of small airways in asthma. However, little information exists about the responsiveness of small airways to various bronchoconstrictors in comparison to large airways. In this study, the model of precision-cut lung slices (PCLSs) was used to investigate the effects of the thromboxane receptor agonist U46619 and endothelin (ET)-1 on small (diameter <250 microm), medium (250-420 microm) and large (>420 microm) airways. Viable PCLSs were prepared from rat lungs and the bronchoconstriction of differently sized airways inducible by U46619 and ET-1 was observed by means of a microscope and analysed by digital imaging techniques. The median effective concentration (EC50) of U46619 for inducing bronchoconstriction was 6.9 nM in small and 66 nM in large airways, respectively. This finding was corroborated by direct observations in single lung slices containing both a small and a large airway. In such slices, U46619 caused smaller airways to contract to a greater degree than larger ones. ET-1 induced bronchoconstriction was similar in small (EC50 34 nM) and in medium or large (ECso 22 nM) airways. This was again confirmed by direct observation of ET-1-treated PCLSs. It is concluded that, in rat lungs, endothelin-1 affects small and large airways to the same extent, whereas thromboxane is ten times more potent in causing small airways to contract than larger ones. Precision-cut lung slices appear to be a valuable model for examining the (patho)physiology of small airways.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

APOE promoter polymorphisms do not confer independent risk for Alzheimer's disease in a French population.

The apolipoprotein E (APOE, gene; apoE, protein) isoforms are associated with differential risk of Alzheimer's disease (AD). An additional involvement of APOE promoter polymorphisms in AD risk has recently been suggested by several studies. Indeed, three polymorphisms of the APOE regulatory region (-219 G/T, -427 C/T and -491 A/T) have been found associated with AD even after adjustment on the apoE status. We analysed these three promoter region polymorphisms in a large French case-control study (388 AD cases and 386 controls). We found that the -427 T and -491 A alleles were associated with an increased risk of developing AD, but not the -219 G/T alleles. However, a strong linkage disequilibrium was observed between the alleles of these promoter region polymorphisms and the APOE coding region alleles. We therefore retested association after adjustment on apoE status and found that the sole association which remained significant was the association with the -427 T allele. The alpha level was equal to 0.03 (0.09 after Bonferroni correction for multiple comparisons). Analysis of promoter haplotypes also yielded non-significant results. Thus our study does not reinforce the hypothesis of an independent involvement of the APOE promoter region polymorphisms in AD risk.

Adult↗

Prevalence of tuberculosis infection among homeless young people in central and eastern Sydney.

OBJECTIVE: To determine the prevalence of tuberculosis (TB) infection among homeless young people (aged 12-25 years) in central and eastern Sydney. METHODOLOGY: A cross-sectional survey was conducted in 16 youth refuges and four drop-in centres in Central and Eastern Sydney Health Areas and at the Cellblock Youth Health Centre, Glebe and the Kirketon Road Centre, Darlinghurst, New South Wales (NSW). Participants completed a questionnaire and underwent Mantoux testing. RESULTS: One hundred and forty-one young people completed questionnaires and 139 received a Mantoux test; 112 (80. 6%) had their Mantoux read and 10 (8.9%) were Mantoux positive (95% confidence interval 3.6-14.2). None of the risk factors examined were found to be associated with increased risk for TB infection. CONCLUSIONS: In this sample of homeless young people in central and eastern Sydney, the Mantoux positivity rate appears to be higher than the general population in NSW, but they would not currently be considered a high-risk group for TB infection.

Adolescent↗

Severe Dupuytren's contracture of the proximal interphalangeal joint: treatment by two-stage technique.

Thirty-four patients with a Dupuytren's contracture in excess of 70 degrees of the proximal interphalangeal (PIP) joint were treated by preliminary palmar fasciotomy, release of the accessory collateral ligaments and PIP joint distraction using the S-Quattro for 6 weeks. A formal fasciectomy with full thickness skin graft was then performed 2 weeks after removal of the fixator. There was a mean residual flexion deformity of the PIP joint of 22 degrees (mean correction of 67 degrees) at an average follow-up of 30 months. There were no infections or amputations. We recommend this technique for the management of severe Dupuytren's contracture of the PIP joint.

Aged↗

General surgery and fellowship training: opinions of surgical intern applicants and fellowship directors.

BACKGROUND: Given the pressures that exist today to modify surgical training programs, this study was undertaken to ascertain the opinions of surgical intern applicants and fellowship program directors with regard to the length of surgical training. METHODS: Surveys were sent to fourth-year medical students who were applying for categorical surgical training during a 2-year period at a single university medical center and to fellowship program directors in 6 surgical subspecialties. RESULTS: Ninety-three percent of the applicants planned to pursue fellowship training. Sixty-eight percent of the applicants did not feel that 5 years of general surgery are necessary before beginning a fellowship. Seventy-one percent of the applicants indicated that they would be willing to "short track" into a subspecialty to reduce training time. Virtually all fellowship directors in pediatric surgery (94%), transplantation surgery (94%), and oncologic surgery (100%) felt that 5 years of general surgery training are necessary before entering a fellowship. Significantly fewer fellowship directors in vascular surgery (53%), cardiothoracic surgery (30%), and plastic surgery (17%) felt that 5 years of general surgery are essential before beginning a fellowship (P < or = .001). CONCLUSIONS: For some general surgery subspecialties, a shortened, integrated training program may be desirable from the point of view of both trainees and fellowship directors. Vascular, cardiothoracic, and plastic surgery appear to be those subspecialties that are most amenable to such programs.

Data Collection↗

High frequency in esophageal cancers of p53 alterations inactivating the regulation of genes involved in cell cycle and apoptosis.

Somatic mutations of the tumor suppressor gene p53 have been frequently detected in esophagal cancers, but their biological significance remains to be established. The tumor suppressor activity of p53 results in part from its ability to transactivate genes involved in the cell cycle and apoptosis, such as p21, bax and PIG3, and some p53 mutations may have a differential effect on the transactivation of these target genes. We developed yeast strains in which the activation by wild-type p53 of reporter plasmids containing p53 binding sites present within these target genes induces a change in the color of the colonies (red/white). Using these strains, we analyzed 56 esophageal cancers from patients residing in Normandy, France, a high incidence geographic area. Forty-seven tumors (84%), scored as mutant with the p21, bax and PIG3 reporter strains and in most of the cases (76%), the percentage of red colonies suggested that both p53 alleles were inactivated. Sequencing analysis allowed the identification of a p53 mutation in each positive sample, and the spectrum of mutations was in agreement with the etiological role of tobacco and alcohol. These results confirm the high frequency of biallelic p53 mutations in esophageal carcinoma and strongly suggest that their biological consequence is the complete alteration of the transactivation of genes involved in the cell cycle and apoptosis, which indicates that p53 alteration is a key event in esophagus carcinogenesis.

Apoptosis↗