Bilateral sensorineural hearing loss and spastic paraparesis in Lyme disease.
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Biomedical subjects
Publications and source records attributed to C Martin.
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Previously reported mutations involved in optochin resistance of Streptococcus pneumoniae clinical isolates changed residues 48, 49 or 50, in the transmembrane alpha-helix 2 of the F(1)/F(0) ATPase subunit. We report here an unusual mutation which changes the sequence of the transmembrane alpha-helix 1 of the AtpC subunit. This mutation involves a Gly to Ser substitution resulting from a G to A transition at codon 14 of the atpC gene.
OBJECTIVES: Nosocomial urinary tract infections associated with bladders catheters are common and poorly understood. Data on the prevention of urinary tract infections are numerous and heterogenous. This update article aimed at analysing mechanisms, epidemiology and prevention of these infections. DATA SOURCES: We searched in the Medline database for articles in English or French, without limiting date of publication, using the following key words separely or in combination: urinary tract infection, nosocomial, catheter, infection urinaire, sonde urinaire. STUDY SELECTION: We considered all categories of articles. DATA EXTRACTION: Data on prevention of nosocomial urinary tract infections were analysed in depth. DATA SYNTHESIS: The data on pathogenesis of nosocomial urinary tract infections are still controversial. Various means for preventing urinary tract infections have been recommended: addition of antibacterial agents to urinary drainage system, inclusion of antimicrobial components into the catheter itself, antibiotic prophylaxis or closed sterile drainage system. Their efficiency in intensive therapy unit has not yet been fully assessed. The therapy of these infections is still under debate and requires additional prospective studies to establish the optimal management. CONCLUSION: Catheter-associated urinary tract infections reflect the general hygiene policy, starting with nurse practice patterns at catheter insertion, and ending with antibio-therapy prescriptions by medical staff.
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.
Every scientific article has to undergo a critical reading before its conclusions can be accepted. This article discusses the tools for assessing the scientific value of a study. A sequence of methodological criteria allows quality evaluation of an article and its classification in a scale of level of proof.
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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.
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.
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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.
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.
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.
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.
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.
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.
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.
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.
OBJECTIVE: The aim of this study was to determine whether changing heat and moisture exchangers (HMEs) every 96 hrs rather than 24 hrs would affect their efficacy to preserve the heat and moisture of inspiratory gases. The impact of a prolonged use of the HME on its microbial colonization was also assessed. DESIGN: Prospective cohort observational study. SETTING: Intensive care unit of a university hospital. PATIENTS: Thirteen consecutive patients with no previous history of respiratory disease requiring controlled mechanical ventilation with an HME for >4 days were evaluated. INTERVENTIONS: The same HME was used for 96 hrs in each patient. MEASUREMENTS AND MAIN RESULTS: In each patient, during the inspiration phase, the following measurements were performed: peak and mean airway pressures, mean values of temperature, and relative and absolute humidity of inspired gases. In each patient, measurements were performed after 1 hr of HME use and then daily up to the fourth day. On days 1 and 4, microbiological samples were obtained from the patients' bronchial secretions and the ventilator side of the HME. After 96 hrs of ventilation with the same HME, tracheal tube occlusion was never observed. Using the same HME for 96 hrs rather than 24 hrs did not affect its technical performances: temperature at 24 hrs: 32.2 +/- 1.5 degrees C (90.0 +/- 34.7 degrees F), at 96 hrs: 32.1 +/- 1.6 degrees C (89.8 +/- 34.9 degrees F); relative humidity at 24 hrs: 97.9 +/- 2%, at 96 hrs: 98.1 +/- 1.7%; absolute humidity at 24 hrs: 33.1 +/- 2.4 mg H2O/L, at 96 hrs: 33.0 +/- 2.5 mg H2O/L. This analysis was based on a total of 312 measurements performed on the 13 patients. Peak and mean airway pressures did not change during the 96-hr study period, with identical tidal and minute volumes in the study patients. On day 1, ten patients had a positive culture of their tracheal secretions at a colony count of > or = 10(3) colony forming units/mL. After 96 hrs of use with the same HME, only seven patients had a positive culture of their tracheal secretions. Cultures from the ventilator sides of the HMEs were all sterile (13/13) after 96 hrs of use. CONCLUSIONS: In patients free from previous chronic respiratory disorder and ventilated for neurologic reasons, changing the HME after 96 hrs rather than 24 hrs did not affect its technical performance in terms of heat and water preservation of ventilatory gases. There is also some indirect evidence of very little, if any, changes in the HME resistance. No bacterial colonization of the ventilator sides of the HMEs was observed after 96 hrs of use. However, other large clinical trials should be undertaken to confirm the safety of extending the time between HME changes.