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Biomedical subjects

M Paul

Publications and source records attributed to M Paul.

At least 19 recordsLinked to original sources
PubMed2006

Antibiotics for preventing meningococcal infections.

BACKGROUND: Meningococcal disease is a contagious bacterial disease caused by Neisseria meningitidis (N. meningitidis). Household contacts have the highest documented risk of the disease during the first seven days of a case being detected. Prophylaxis is, therefore, considered for those in close contact with people with a meningococcal infection and in populations with known high carriage rates as carriers are at increased risk of disease and may pose a risk of infection to others. OBJECTIVES: To study the effectiveness of different prophylactic treatment regimens in: (1) preventing secondary cases of meningococcal disease after contact with someone with the disease; (2) preventing cases of meningococcal disease in populations with a high rate of N. meningitidis carriers; (3) eradicating N. meningitidis from the pharynx in healthy carriers of N. meningitidis. This review also addresses the issues of adverse effects of prophylaxis and development of drug resistance. SEARCH STRATEGY: Electronic searches on the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2006), MEDLINE (January 1966 to June 2006), EMBASE (1980 to June 2006), LILACS (1982 to June 2006); and searching of references of all identified studies were performed. SELECTION CRITERIA: Randomised or quasi-randomised clinical trials addressing the effectiveness of different antibiotic treatments for: (a) prophylaxis against meningococcal disease; (b) eradication of N. meningitidis. DATA COLLECTION AND ANALYSIS: Two reviewers independently appraised the quality of each trial and extracted data from the included trials. Dichotomous data were analysed by calculating the relative risk (RR) and 95% confidence interval for each trial. MAIN RESULTS: There were no cases of meningococcal disease during follow up in any of the trials, thus effectiveness regarding prevention of future disease cannot be directly assessed. Ciprofloxacin (RR 0.04; 95% CI 0.01 to 0.12), rifampin (rifampicin) (RR 0.17; 95% CI 0.12 to 0.24), minocycline (RR 0.30; 95% CI 0.19 to 0.45) and ampicillin (RR 0.41; 95% CI 0.25 to 0.66) proved effective at eradicating N. meningitidis one week after treatment when compared with placebo. However, only rifampin (RR 0.20; 95% CI 0.14 to 0.29) and ciprofloxacin (RR 0.03; 95% CI 0.00 to 0.42) still proved effective at one to two weeks. Rifampin continued to be effective compared to placebo for up to four weeks after treatment but resistant isolates were seen following prophylactic treatment. No trials evaluated ceftriaxone against placebo but ceftriaxone was more effective than rifampin after one to two weeks of follow up (RR 5.93; 95% CI 1.22 to 28.68). AUTHORS' CONCLUSIONS: Given the fact that the use of rifampin in an outbreak setting might lead to the circulation of isolates resistant to rifampin, use of ciprofloxacin or ceftriaxone should be considered. Evidence suggests that all three agents are effective with up to two weeks follow up. Placebo-controlled trials do not seem ethical as prophylactic treatment has been proven to reduce the risk of disease among household contacts. More trials comparing the effectiveness of ceftriaxone, ciprofloxacin and rifampin for eradicating N. meningitidis would provide important insights.

Ampicillin↗
PubMed2006

Highly efficient and specific modulation of cardiac calcium homeostasis by adenovector-derived short hairpin RNA targeting phospholamban.

Impaired function of the phospholamban (PLB)-regulated sarcoplasmic reticulum Ca(2+) pump (SERCA2a) contributes to cardiac dysfunction in heart failure (HF). PLB downregulation may increase SERCA2a activity and improve cardiac function. Small interfering (si)RNAs mediate efficient gene silencing by RNA interference (RNAi). However, their use for in vivo gene therapy is limited by siRNA instability in plasma and tissues, and by low siRNA transfer rates into target cells. To address these problems, we developed an adenoviral vector (AdV) transcribing short hairpin (sh)RNAs against rat PLB and evaluated its potential to silence the PLB gene and to modulate SERCA2a-mediated Ca(2+) sequestration in primary neonatal rat cardiomyocytes (PNCMs). Over a period of 13 days, vector transduction resulted in stable > 99.9% ablation of PLB-mRNA at a multiplicity of infection of 100. PLB protein gradually decreased until day 7 (7+/-2% left), whereas SERCA, Na(+)/Ca(2+) exchanger (NCX1), calsequestrin and troponin I protein remained unchanged. PLB silencing was associated with a marked increase in ATP-dependent oxalate-supported Ca(2+) uptake at 0.34 microM of free Ca(2+), and rapid loss of responsiveness to protein kinase A-dependent stimulation of Ca(2+) uptake was maintained until day 7. In summary, these results indicate that AdV-derived PLB-shRNA mediates highly efficient, specific and stable PLB gene silencing and modulation of active Ca(2+) sequestration in PNCMs. The availability of the new vector now enables employment of RNAi for the treatment of HF in vivo.

Animals↗
PubMed2006

The significance of Acinetobacter baumannii bacteraemia compared with Klebsiella pneumoniae bacteraemia: risk factors and outcomes.

Risk factors and outcomes for patients with nosocomial Acinetobacter baumannii bacteraemia were compared with those for patients with nosocomial Klebsiella pneumoniae bacteraemia in a single centre in Israel between 2000 and 2003. Data were collected retrospectively through patient chart review. In total, 112 patients with A. baumannii bacteraemia and 90 patients with K. pneumoniae bacteraemia were identified. A. baumannii was significantly associated with poorer performance status, mechanical ventilation, presence of devices, prior treatment with carbapenems, pneumonia as the source of infection and inappropriate empirical antibiotic treatment. All-cause 30-day mortality was higher for A. baumannii bacteraemia compared with K. pneumoniae bacteraemia (61.6% vs 38.9%, P=0.001). Variables significantly associated with mortality at the univariate level (P<0.1) were entered into a multi-variable logistic regression model for mortality. A. baumannii remained significantly associated with mortality when adjusted for all other risk factors (odds ratio 3.61, 95% confidence interval 1.55-8.39). This result did not change when the analysis was repeated for subgroups of less severely ill patients, i.e. those who were not ventilated and those who did not present with septic shock. These results support the view that nosocomial bacteraemia due to A. baumannii is associated with increased mortality.

Acinetobacter Infections↗
PubMed2006

Usefulness of Toxoplasma gondii recombinant antigens (GRA1, GRA7 and SAG1) in an immunoglobulin G avidity test for the serodiagnosis of toxoplasmosis.

The precise diagnosis of an acute and recent Toxoplasma infection in pregnant women and the newborn child is important before treatment. This study describes a new Toxoplasma gondii IgG avidity test based on a combination of recombinant GRA1, GRA7 and SAG1 antigens and shows that this test is useful for diagnostic purposes and may replace the lysed, whole-cell antigens. Although more sera need to be tested, the results obtained here suggest that the IgG avidity test performed with rec-antigens correlated more with the stage of a T. gondii infection than the IgG avidity results obtained with the lysed, whole-cell antigen test, the VIDAS Toxo IgG avidity (bioMérieux).

Animals↗
PubMed2006

Drugs for preventing tuberculosis in people at risk of multiple-drug-resistant pulmonary tuberculosis.

BACKGROUND: The emergence and spread of multiple-drug-resistant tuberculosis (MDR-TB), caused by strains of Mycobacterium tuberculosis resistant to at least isoniazid and rifampicin, is a potential threat to global tuberculosis control. Treatment is prolonged, expensive, more toxic than treatment of susceptible tuberculosis, and often unsuccessful. Experts are still undecided on the management of people exposed to MDR-TB. OBJECTIVES: To evaluate antituberculous drugs given to people exposed to MDR-TB in preventing active tuberculosis. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (January 2006), CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to January 2006); EMBASE (1974 to January 2006), LILACS (1982 to January 2006), conference proceedings, and reference lists. We also contacted researchers and organizations. SELECTION CRITERIA: Randomized controlled trials comparing antituberculous drug regimens with an alternative antituberculous drug regimen, placebo, or no intervention given to people exposed to MDR-TB for preventing active tuberculosis. DATA COLLECTION AND ANALYSIS: Two authors independently inspected titles and abstracts identified by the search in order to identify potentially relevant publications for inclusion and analysis. MAIN RESULTS: No randomized controlled trials met the inclusion criteria. AUTHORS' CONCLUSIONS: The balance of benefits and harms associated with treatment for latent tuberculosis infection in people exposed to MDR-TB is far from clear. Antituberculous drugs should only be offered within the context of a well-designed randomized controlled trial, or when people are given the details of the current evidence on benefits and harms, along with the uncertainties.

Antitubercular Agents↗
PubMed2006

40Ca(alpha, gamma)44Ti reaction in the energy regime of supernova nucleosynthesis.

The 44Ti(t1/2=59 yr) nuclide, an important signature of supernova nucleosynthesis, has recently been observed as live radioactivity by gamma-ray astronomy from the Cas A remnant. We investigate in the laboratory the major 44Ti production reaction 40Ca(alpha, gamma)44Ti (Ec.m. approximately 0.6-1.2 MeV/u by direct off-line counting of 44Ti nuclei. The yield, significantly higher than inferred from previous experiments, is analyzed in terms of a statistical model using microscopic nuclear inputs. The associated stellar rate has important astrophysical consequences, increasing the calculated supernova 44Ti yield by a factor approximately 2 over previous estimates and bringing it closer to Cas A observations.

Journal Article↗
PubMed2006

Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis.

BACKGROUND: Optimal antibiotic treatment for sepsis is imperative. Combining a beta-lactam antibiotic with an aminoglycoside antibiotic may have certain advantages over beta-lactam monotherapy. OBJECTIVES: We compared clinical outcomes for beta lactam-aminoglycoside combination therapy versus beta lactam monotherapy for sepsis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 3, 2004); MEDLINE (1966 to July 2004); EMBASE (1980 to March 2003); LILACS (1982 to July 2004); and conference proceedings of the Interscience Conference of Antimicrobial Agents and Chemotherapy (1995 to 2003). We scanned citations of all identified studies and contacted all corresponding authors. SELECTION CRITERIA: We included randomized and quasi-randomized trials comparing any beta-lactam monotherapy to any combination of one beta-lactam and one aminoglycoside for sepsis. DATA COLLECTION AND ANALYSIS: The primary outcome was all-cause fatality. Secondary outcomes included treatment failure, superinfections, colonization, and adverse events. Two authors independently collected data. We pooled relative risks (RR) with their 95% confidence intervals (CI) using the fixed effect model. We extracted outcomes by intention-to-treat analysis whenever possible. MAIN RESULTS: We included 64 trials, randomizing 7586 patients. Twenty trials compared the same beta-lactam in both study arms, while the remaining compared different beta-lactams using a broader spectrum beta-lactam in the monotherapy arm. In studies comparing the same beta-lactam, we observed no difference between study groups with regard to all-cause fatality, RR 1.01 (95% CI 0.75-1.35) and clinical failure, RR 1.11 (95% CI 0.95-1.29). In studies comparing different beta-lactams, we observed an advantage to monotherapy: all cause fatality RR 0.85 (95% CI 0.71-1.01), clinical failure RR 0.77 (95% CI 0.69-0.86). No significant disparities emerged from subgroup and sensitivity analyses, including the assessment of patients with Gram-negative and Pseudomonas aeruginosa infections. We detected no differences in the rate of resistance development. Adverse events rates did not differ significantly between the study groups overall, although nephrotoxicity was significantly more frequent with combination therapy, RR 0.30 (95% CI 0.23-0.39). We found no heterogeneity for all comparisons. We included a small subset of studies addressing patients with Gram-positive infections, mainly endocarditis. We identified no difference between monotherapy and combination therapy in these studies. AUTHORS' CONCLUSIONS: The addition of an aminoglycoside to beta-lactams for sepsis should be discouraged. All-cause fatality rates are unchanged. Combination treatment carries a significant risk of nephrotoxicity.

Aminoglycosides↗
PubMed2006

[First clinical experience with a video presentation informing patients before surgery for inguinal hernia].

BACKGROUND: Although it is a significant part of surgical treatment, informing patients beforehand seems to be more and more neglected, mainly due to the enormous amount of work and time pressure on surgical personnel. MATERIAL AND METHODS: A video clip explaining groin hernia surgical repair was produced as additional information for patients. In it, visual material from actual practice describes the disease, the operation itself, all the perioperative aspects, and patients' own experiences. In a prospective comparison study, the length of patient education, its quality, patient satisfaction, and the duration of hospitalization and time off work were compared between patients who saw the video clip (n=50) and those who did not (n=50). RESULTS AND CONCLUSION: In summary, the time spent informing the video group was shorter (P<0.05) and their total satisfaction and evaluation of the information material were both higher (P>0.05) for comparable duration of treatment and time off work. This informative video was adopted without problems in our daily clinical life and, besides reducing the time needed to inform patients, it has significantly improved patient understanding of the operative procedure and their satisfaction with treatment.

Adult↗
PubMed2006

Mechanisms of apoptosis after ischemia and reperfusion: role of the renin-angiotensin system.

BACKGROUND: Apoptosis plays a key role in the pathogenesis of cardiac diseases. We examined the influence of the renin-angiotensin system (RAS) on different regulators of apoptosis using an isolated hemoperfused working porcine heart model of acute ischemia (2 h), followed by reperfusion (4 h). METHODS AND RESULTS: 23 porcine hearts were randomized to 5 groups: hemoperfused non-infarcted hearts (C), infarcted hearts (MI: R. circumflexus), infarcted hearts treated with quinaprilat (Q), infarcted hearts treated with angiotensin-I (Ang I), and infarcted hearts treated with angiotensin-I and quinaprilat (QA). Fas, Bax, bcl-2 and p53 proteins were increased in MI hearts and further elevated by Ang I. Quinaprilat reduced Bax and p53. Bcl-2 was elevated in Q and reduced in QA. An early upregulation of caspase-3 gene and protein expression was detected in MI and Ang I hearts compared to C. Q reduced caspase-3 gene expression, but had no effect on caspase-3 and Fas protein. CONCLUSIONS: These data suggest that the RAS plays a pivotal role in cardiac apoptosis which is the early and predominant form of death in myocardial infarction. Ischemia/reperfusion induces programmed cell death via extrinsic and intrinsic pathways. Early treatment with quinaprilat attenuated cardiomyocyte apoptosis.

Angiotensin I↗
PubMed2006

Induction of three-dimensional assembly and increase in apoptosis of human endothelial cells by simulated microgravity: impact of vascular endothelial growth factor.

Endothelial cells play a crucial role in the pathogenesis of many diseases and are highly sensitive to low gravity conditions. Using a three-dimensional random positioning machine (clinostat) we investigated effects of simulated weightlessness on the human EA.hy926 cell line (4, 12, 24, 48 and 72 h) and addressed the impact of exposure to VEGF (10 ng/ml). Simulated microgravity resulted in an increase in extracellular matrix proteins (ECMP) and altered cytoskeletal components such as microtubules (alpha-tubulin) and intermediate filaments (cytokeratin). Within the initial 4 h, both simulated microgravity and VEGF, alone, enhanced the expression of ECMP (collagen type I, fibronectin, osteopontin, laminin) and flk-1 protein. Synergistic effects between microgravity and VEGF were not seen. After 12 h, microgravity further enhanced all proteins mentioned above. Moreover, clinorotated endothelial cells showed morphological and biochemical signs of apoptosis after 4 h, which were further increased after 72 h. VEGF significantly attenuated apoptosis as demonstrated by DAPI staining, TUNEL flow cytometry and electron microscopy. Caspase-3, Bax, Fas, and 85-kDa apoptosis-related cleavage fragments were clearly reduced by VEGF. After 72 h, most surviving endothelial cells had assembled to three-dimensional tubular structures. Simulated weightlessness induced apoptosis and increased the amount of ECMP. VEGF develops a cell-protective influence on endothelial cells exposed to simulated microgravity.

Apoptosis↗
PubMed2006

Mechanisms of killing of spores of Bacillus subtilis by dimethyldioxirane.

AIMS: To determine the mechanisms of Bacillus subtilis spore resistance to and killing by a novel sporicide, dimethyldioxirane (DMDO) that was generated in situ from acetone and potassium peroxymonosulfate at neutral pH. METHODS AND RESULTS: Spores of B. subtilis were effectively killed by DMDO. Rates of killing by DMDO of spores lacking most DNA protective alpha/beta-type small, acid-soluble spore proteins (alpha- beta- spores) or the major DNA repair protein, RecA, were very similar to that of wild-type spore killing. Survivors of wild-type and alpha- beta- spores treated with DMDO also exhibited no increase in mutations. Spores lacking much coat protein due either to mutation or chemical decoating were much more sensitive to DMDO than were wild-type spores, but were more resistant than growing cells. Wild-type spores killed with this reagent retained their large pool of dipicolinic acid (DPA), and the survivors of spores treated with DMDO were sensitized to wet heat. The DMDO-killed spores germinated with nutrients, albeit more slowly than untreated spores, but germinated faster than untreated spores with dodecylamine. The killed spores were also germinated by very high pressures and by lysozyme treatment in hypertonic medium, but many of these spores lysed shortly after their germination, and none of these treatments were able to revive the DMDO-killed spores. CONCLUSIONS: DMDO is an effective reagent for killing B. subtilis spores. The spore coat is a major factor in spore resistance to DMDO, which does not kill spores by DNA damage or by inactivating some component needed for spore germination. Rather, this reagent appears to kill spores by damaging the spore's inner membrane in some fashion. SIGNIFICANCE AND IMPACT OF THE STUDY: This work demonstrates that DMDO is an effective decontaminant for spores of Bacillus species that can work under mild conditions, and the killed spores cannot be revived. Evidence has also been obtained on the mechanisms of spore resistance to and killing by this reagent.

Anti-Bacterial Agents↗
PubMed2006

Treatment of latent tuberculosis in persons at risk for multidrug-resistant tuberculosis: systematic review.

SETTING: The emergence and spread of multidrug-resistant tuberculosis (MDR-TB), caused by Mycobacterium tuberculosis resistant to at least isoniazid (INH) and rifampicin, is a threat to global TB control. OBJECTIVE: To appraise evidence of the effectiveness of treatment of latent TB infection (LTBI) in people at risk for developing active MDR-TB. DESIGN: Systematic review of comparative studies of people treated and not treated for LTBI following exposure to MDR-TB. DATA SOURCES: PubMed, EMBASE, LILACS and the Cochrane Library (December 2004). RESULTS: Two observational studies met inclusion criteria. A prospective cohort study found individualised tailored treatment to be effective for preventing active TB in children (OR = 0.20, 95%CI 0.04-0.94), while a retrospective cohort study found INH not to be effective (OR = 0.46, 95%CI 0.07-2.32). CONCLUSION: Evidence of the effects of treatment of LTBI in people exposed to MDR-TB is extremely limited in both quantity and quality. The increasing global spread of MDR-TB and the difficulties in treating it emphasise the need for effective preventive measures. Ideally, this issue should be addressed in a randomised controlled trial. Until such a trial is conducted, routine clinical data collected as part of existing TB control programmes could be useful and can be generated relatively easily.

Antitubercular Agents↗
PubMed2005

[New tendencies in combination antihypertensive therapy].

In the management of hypertension, the constant lowering of target pressures ever more frequently requires combination treatment in order to achieve the goals set. A combination of amlodipine and perindopril effectively lowered the blood pressure, and significantly reduced overall mortality, cardiovascular mortality, cardiovascular events and stroke risk in comparison with atenolol/bendroflumethiazide. In combination with both ACE inhibitors and AT1 blockers, diuretics reduced blood pressure more effectively that the respective components used alone. Now, however, the long-term use of diuretics is suspected of increasing the risk of terminal kidney failure and diabetes. This also means an enhanced probability of a cardiovascular event. In the ASCOT study, the combination of beta blocker and diuretic proved inferior to treatment with a calcium antagonist and ACE inhibitor. For the long-term application of diuretics as antihypertensive monotherapy, therefore, further comparative studies involving the latest antihypertensives are mandatory.

Antihypertensive Agents↗
PubMed2005

Evaluation of skin viscoelasticity in type 1 neurofibromatosis patients.

Neurofibromatosis type 1 (NF1) is a frequent autosomal dominant disease characterized by cutaneous benign tumors called neurofibromas. Surgery takes an important place in managing these skin disorders. However, skin distensibility and softness of NF1 patients quickly offset the surgical benefit. The aim of this study was to determine the rheological behavior of neurofibromas and compare it with healthy skin in an attempt to comprehend what leads to this phenomenon. Thirty patients were admitted to this study. A group of 24 healthy control subjects was also included. The skin elasticity was assessed by a noninvasive in vivo suction device (Cutometer) including 5 consecutive suctions. The assessments were performed on neurofibroma skin, the supposedly healthy skin around neurofibromas and the healthy skin of control subjects. The extensibility at the first and the fifth traction in NF1 patients (neurofibromas and the supposedly healthy skin around it) was significantly different compared to the healthy skin of control subjects. The viscoelastic parameters obtained from the neurofibromas were significantly different in comparison to those obtained from the supposedly healthy skin of NF1 patients and the healthy skin of control subjects. The rheological profiles of the neurofibromas and the apparent healthy skin of NF1 patients demonstrated a hyperextensibility behavior, but in neurofibromas, the skin was unable to return to its initial position at the end of the stretch.

Adolescent↗