A comparison of Listerine® and sodium bicarbonate oral cleansing solutions on dental plaque colonisation and incidence of ventilator associated pneumonia in mechanically ventilated patients: a randomised control trial.

BACKGROUND: Effective oral hygiene has been proposed as a key factor in the reduction of dental plaque colonisation and subsequent development of ventilator associated pneumonia (VAP). Listerine(®) oral rinse, while used extensively in dental practice has rarely been tested in mechanically ventilated patients. Sodium bicarbonate as an oral rinse has been more commonly utilised in oral hygiene regimens in intensive care patients. AIM: To test the efficacies of the essential oil mouth rinse, Listerine(®) (Pfizer) and sodium bicarbonate in the reduction of dental plaque colonisation with respiratory pathogens and the subsequent development of VAP. METHODS: The study design was a prospective, single blind randomised comparative study of adult patients mechanically ventilated for at least 4 days. Patients were randomised to Listerine(®) (Pfizer) oral rinse twice daily, sodium bicarbonate oral rinse 2/24 or sterile water 2/24 (control group). All groups received tooth brushing 3 times a day. Dental plaque colonisation (primary outcome) and incidence of ventilator associated pneumonia (secondary outcome) were studied. RESULTS: Three hundred and ninety-eight patients were randomised to either the Listerine group (127), sodium bicarbonate group (133) or the control group (138). Baseline characteristics were similar for all groups. There were no significant differences between the control and study groups in colonisation of dental plaque at Day 4 (p=0.243). Ventilator associated pneumonia was diagnosed in 18 patients. The incidence was, Listerine(®) group 4.7%, sodium bicarbonate group 4.5% and control 4.3% [OR, 0.99; 95% CI, 0.31 to 3.16; p=0.92]. CONCLUSIONS: Compared to the control group, Listerine(®) or sodium bicarbonate oral rinses were not more effective in the reduction of colonisation of dental plaque or the incidence of VAP. Given the low incidence of VAP, the common factor of a small, soft toothbrush as part of an oral hygiene regimen suggests possible benefit in mechanically ventilated patients.

Effects of three approaches to standardized oral hygiene to reduce bacterial colonization and ventilator associated pneumonia in mechanically ventilated patients: a randomised control trial.

BACKGROUND: Ventilator associated pneumonia remains an important concern in the intensive care unit (ICU). An increasing body of evidence shows that mortality and morbidity can be reduced by implementing a range of preventive strategies, including optimizing oral hygiene. AIM: The aim of this feasibility study was to test two oral hygiene strategies on the effects of microbial colonization of dental plaque with respiratory pathogens (primary outcome) and incidence of ventilator associated pneumonia (secondary outcome). METHODS: A single blind randomised comparative study was conducted in a 20-bed adult intensive care unit in a university hospital. Patients with an expected duration of mechanical ventilation more than 48 h were eligible. Patients were randomised to one of three study regimens (Group A control, second hourly oral rinse with sterile water, Group B sodium bicarbonate mouth wash second hourly, and Group C twice daily irrigations with chlorhexidine 0.2% aqueous oral rinse and second hourly irrigations with sterile water). All study options included cleaning with a toothbrush and non foaming toothpaste. RESULTS: Data from a total of 109 patients were analyzed. Group A 43, Group B 33 and Group C 33 (mean age: 58 ± 17 years, simplified acute physiology score II: 44 ± 14 points). On admission no significant differences were found between groups for all clinical data. While Group B showed a greater trend to reduction in bacterial colonization no significant differences could be demonstrated at Day 4 of admission (p=0.302). The incidence of ventilator associated pneumonia was evenly spread between Groups B and C (5%) while Group A was only 1%. CONCLUSIONS: While a number of studies have advocated the use of various mouth rinses in reducing colonization of dental plaque a standardized oral hygiene protocol which includes the use of mechanical cleaning with a toothbrush may be a factor in the reduction of colonization of dental plaque with respiratory pathogens. This feasibility study provides data to inform future adequately powered studies.

Novel hypothesis for unexplained sudden unexpected death in infancy (SUDI).

OBJECTIVE: Two recent retrospective studies independently reported typically pathogenic bacteria in normally sterile sites of infants succumbing to sudden unexpected death in infancy (SUDI). These findings suggested a proportion of unexplained SUDI might be triggered by bacteraemia. The objective was to assess these observations in the context of the pathology and epidemiology of sudden infant death syndrome (SIDS) in relation to the role of infection and inflammation as triggers of these deaths. DESIGN: A review of the literature to identify potential risk factors for unexplained infant deaths and proposal of a theoretical model for SUDI. RESULTS: Pathologic and epidemiological evidence suggests a hypothesis based on three factors: bacterial translocation, pathogen pattern recognition insufficiency and prenatal exposure to infection. CONCLUSION: We propose that sterile site infections in which common toxigenic bacteria are identified indicate a brief bacteraemic episode prior to death. This might reflect an ineffective innate response to invasive pathogens that results in reduced clearance of the bacteria. Thymomegaly observed consistently among infants diagnosed under the category of SIDS might have its origins in prenatal life, perhaps generated via in utero infection or exposure to microbial antigens which results in thymocyte priming. There is consistent evidence for an infectious aetiology in many unexplained SUDI. Future directions for research are suggested.

Fractured penis: a review.

Fracture of the penis is a well-recognized clinical entity. The ideal management has evolved and repair remains largely surgical. We present the etiology and pathophysiology of this condition and outline the therapeutic options.

Truncated hemoglobins in actinorhizal nodules of Datisca glomerata.

Three types of hemoglobins exist in higher plants, symbiotic, non-symbiotic, and truncated hemoglobins. Symbiotic (class II) hemoglobins play a role in oxygen supply to intracellular nitrogen-fixing symbionts in legume root nodules, and in one case ( Parasponia Sp.), a non-symbiotic (class I) hemoglobin has been recruited for this function. Here we report the induction of a host gene, dgtrHB1, encoding a truncated hemoglobin in Frankia-induced nodules of the actinorhizal plant Datisca glomerata. Induction takes place specifically in cells infected by the microsymbiont, prior to the onset of bacterial nitrogen fixation. A bacterial gene (Frankia trHBO) encoding a truncated hemoglobin with O (2)-binding kinetics suitable for the facilitation of O (2) diffusion ( ) is also expressed in symbiosis. Nodule oximetry confirms the presence of a molecule that binds oxygen reversibly in D. glomerata nodules, but indicates a low overall hemoglobin concentration suggesting a local function. Frankia trHbO is likely to be responsible for this activity. The function of the D. glomerata truncated hemoglobin is unknown; a possible role in nitric oxide detoxification is suggested.

Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats.

Arterial calcification (AC) is generally regarded as an independent risk factor for cardiovascular morbidity and mortality. Matrix Gla protein (MGP) is a potent inhibitor of AC, and its activity depends on vitamin K (VK). In rats, inactivation of MGP by treatment with the vitamin K antagonist warfarin leads to rapid calcification of the arteries. Here, we investigated whether preformed AC can be regressed by a VK-rich diet. Rats received a calcification-inducing diet containing both VK and warfarin (W&K). During a second 6-week period, animals were randomly assigned to receive either W&K (3.0 mg/g and 1.5 mg/g, subsequently), a diet containing a normal (5 microg/g) or high (100 microg/g) amount of VK (either K1 or K2). Increased aortic calcium concentration was observed in the group that continued to receive W&K and also in the group changed to the normal dose of VK and AC progressed. Both the VK-rich diets decreased the arterial calcium content by some 50%. In addition, arterial distensibility was restored by the VK-rich diet. Using MGP antibodies, local VK deficiency was demonstrated at sites of calcification. This is the first study in rats demonstrating that AC and the resulting decreased arterial distensibility are reversible by high-VK intake.

Novel effects of diets enriched with corn oil or with an olive oil/sunflower oil mixture on vitamin K metabolism and vitamin K-dependent proteins in young men.

Little is known of how the fat components of diets influence the absorption and metabolism of vitamin K and the possible consequences to the synthesis of vitamin K-dependent (VKD) proteins in different target organs. We have evaluated the effects of two diets on circulating phylloquinone (K1) and triacylglycerols (TAG). One diet was enriched with corn oil (CO) (also rich in gamma-tocopherol) and the other with an olive/sunflower (O/SO) mixture (rich in alpha-tocopherol). Effects on gamma-carboxylation were assessed from coagulation assays and sensitive assays for undercarboxylated prothrombin (ucFII) and osteocalcin (ucOC). Total plasma matrix Gla-protein (MGP) was also measured. After an initial adjustment diet, 26 healthy young men were fed, in a crossover design, the O/SO or CO diet for 2 weeks. Mean intakes of K1 during consumption of adjustment, O/SO, and CO diets were 225 microg/day, 291 microg/day, and 291 microg/day, respectively. Mean fasting levels of TAG and K1 were both significantly reduced by the CO diet, but not by the O/SO diet. Neither diet reduced FII activity but ucFII became detectable in nine subjects, eight of whom showed this abnormality with both diets. The CO diet induced a rise in ucOC (P < 0.05), which was negatively correlated to ucFII (r = -0.71, P < 0.03). The CO but not O/SO diet induced a decrease of total circulating MGP. We conclude that both oils, notably CO, affected vitamin K absorption and/or metabolism which may increase the requirements for gamma-carboxylation. The mechanism is unclear but may result from interactions of vitamin K with PUFA and/or other lipid components such as vitamin E.

Characteristics and composition of the vitamin K-dependent gamma-glutamyl carboxylase-binding domain on osteocalcin.

Two different sites on vitamin K-dependent gamma-glutamyl carboxylase (VKC) are involved in enzyme-substrate interaction: the propeptide-binding site required for high-affinity substrate binding and the active site for glutamate carboxylation. Synthetic descarboxy osteocalcin (d-OC) is a low-K(m) substrate for the VKC, but unique since it possesses a high-affinity recognition site for the VKC, distinct from the propeptide which is essential as a binding site for VKC. However, the exact location and composition of this VKC-recognition domain on d-OC has remained unclear until now. Using a stereospecific substrate analogue [t-butyloxycarbonyl-(2S,4S)-4-methylglutamic acid-Glu-Val (S-MeTPT)] we demonstrate in this paper that the high affinity of d-OC for VKC cannot be explained by a direct interaction with either the active site or with the propeptide-binding site on VKC. It is shown using various synthetic peptides derived from d-OC that there are two domains on d-OC necessary for recognition: one located between residues 1 and 12 and a second between residues 26 and 39, i.e. at the C-terminal side of the gamma-carboxyglutamate (Gla) domain. Both internal sequences contribute substantially to the efficiency of carboxylation. On the basis of these data we postulate the presence of a second high-affinity substrate-binding site on VKC capable of specifically binding d-OC, which is the first vitamin K-dependent substrate of which the VKC binding domain is interrupted by the Gla domain.

Hopanoid lipids in Frankia: identification of squalene-hopene cyclase gene sequences.

In Frankia, the microsymbiont in actinorhizal root nodules, nitrogen fixation takes place in specialized structures called vesicles. The lipidic vesicle envelope forms a barrier to oxygen diffusion, an essential part of the nitrogenase oxygen protection system. We have shown previously that the vesicle envelope is composed primarily of two species of hopanoid lipids, sterol-like molecules that are synthesized in a wide range of bacteria, including Frankia, several cyanobacteria, and rhizobia. The levels of hopanoid found in Frankia are among the highest of any organism known to date. Here we report that short (328-bp) DNA sequences from several strains of Frankia spp. have been identified that are homologous to a portion of the coding region of squalene-hopene cyclase (shc) genes. The fragments and corresponding polymerase chain reaction (PCR) primers can be used in phylogenetic comparisons of Frankia, both within Frankiaceae and among bacteria that synthesize hopanoids.

Genetic characterization of vanG, a novel vancomycin resistance locus of Enterococcus faecalis.

Enterococcus faecalis strain WCH9 displays a moderate level of resistance to vancomycin (MIC = 16 microgram/ml) and full susceptibility to teicoplanin but is negative by PCR analysis using primers specific for all known enterococcal vancomycin resistance genotypes (vanA, vanB, vanC, vanD, and vanE). We have isolated and sequenced a novel putative vancomycin resistance locus (designated vanG), which contains seven open reading frames, from this strain. These are organized differently from those of all the other enterococcal van loci, and, furthermore, the individual vanG gene products exhibit less than 50% amino acid sequence identity to other van gene products.

Dg93, a nodule-abundant mRNA of Datisca glomerata with homology to a soybean early nodulin gene.

We have isolated a 590-bp full-length cDNA clone designated Dg93, an mRNA that is highly expressed in symbiotic root nodules of the actinorhizal host Datisca glomerata. Dg93 mRNA encodes a deduced polypeptide of 105 amino acids with significant identity (74%) to the soybean (Glycine max) early nodulin (ENOD) gene GmENOD93 (Kouchi and Hata, 1993). Dg93 mRNA is abundant in nodules at 4 weeks post inoculation, the earliest time assayed, and steady-state mRNA levels remain elevated 11 weeks after inoculation. Spatial patterns of Dg93 mRNA expression are complex, with transcript accumulation in the nodule lobe meristem, early infection zone, periderm, and cells of the vascular cylinder, but not in the surrounding uninfected cortical cells. Dg93 is encoded by a small gene family in D. glomerata. To our knowledge, this is the first report of a gene from an actinorhizal host that is expressed in the nodule meristem and that shares sequence homology with an early nodulin gene from a legume.

Additive attenuation of virulence of Streptococcus pneumoniae by mutation of the genes encoding pneumolysin and other putative pneumococcal virulence proteins.

Although the polysaccharide capsule of Streptococcus pneumoniae has been recognized as a sine qua non of virulence, much recent attention has focused on the role of pneumococcal proteins in pathogenesis, particularly in view of their potential as vaccine antigens. The individual contributions of pneumolysin (Ply), the major neuraminidase (NanA), autolysin (LytA), hyaluronidase (Hyl), pneumococcal surface protein A (PspA), and choline-binding protein A (CbpA) have been examined by specifically mutagenizing the respective genes in the pneumococcal chromosome and comparing the impact on virulence in a mouse intraperitoneal challenge model. Mutagenesis of either the ply, lytA, or pspA gene in S. pneumoniae D39 significantly reduced virulence, relative to that of the wild-type strain, indicating that the respective gene products contribute to pathogenesis. On the other hand, mutations in nanA, hyl, or cbpA had no significant impact. The virulence of D39 derivatives carrying a ply deletion mutation as well as an insertion-duplication mutation in one of the other genes was also examined. Mutagenesis of either nanA or lytA did not result in an additional attenuation of virulence in the ply deletion background. However, significant additive attenuation in virulence was observed for the strains with ply-hyl, ply-pspA, and ply-cbpA double mutations.

Symbiotic root nodules of the actinorhizal plant Datisca glomerata express Rubisco activase mRNA.

N2-fixing symbiotic root nodules of the actinorhizal host Datisca glomerata express Dgrca (D. glomerata Rubisco activase) mRNA, a transcript usually associated with photosynthetic organs or tissues. In northern blots a mature, 1700-nucleotide Dgrca mRNA was detected in green plant organs (leaves, flowers, and developing fruits) and in nodules but was not detected in roots. A second message of 3000 nucleotides was observed only in nodules. Both size classes of transcripts were polyadenylated. The larger transcript was 2- to 5-fold more abundant than the mature mRNA; it was hybridized to an intronic probe, indicating that a stable, incompletely spliced transcript was accumulating. Treatment with light on excised nodules did not alter the relative abundance of the two species. In in situ hybridizations the Dgrca message was expressed intensely in the nuclei of infected cells. The Dgrca transcripts also accumulated at lower levels in uninfected cortical cells adjacent to the periderm and the vascular cylinder. mRNA encoding the large subunit of Rubisco (DgrbcL) was abundant in mature infected cells and in the amyloplast-rich sheath of uninfected cortical cells lying between the infected cells and nodule periderm. The proteins Rubisco activase, Rubisco, and the 33-kD O2-evolving complex subunit did not accumulate to detectable levels, indicating that a functional photosynthetic apparatus was not prevalent in nodule tissue. Signals or factors required for the transcription of Dgrca appeared to be present in nodules, but efficient splicing and translation of the message were not observed in Frankia-infected tissue where transcript accumulation was highest.

Comparative virulence of Streptococcus pneumoniae strains with insertion-duplication, point, and deletion mutations in the pneumolysin gene.

Pneumolysin is a 471-amino-acid toxin produced by Streptococcus pneumoniae which has both cytolytic and complement activation properties. We have constructed a derivative of the type 2 S. pneumoniae strain D39 in which the portion of the pneumolysin gene encoding amino acids 55 to 437 has been deleted in-frame. The virulence of this strain (DeltaPly) was compared with those of wild-type D39, a pneumolysin insertion-duplication mutant (PLN-A), and a derivative (PdT) carrying a toxin gene with three point mutations known to abolish both cytolytic activity and complement activation. PdT was intermediate in virulence between D39 and either PLN-A or DeltaPly in a mouse intraperitoneal challenge model. This provides unequivocal evidence that pneumolysin has an additional property that is not abolished by point mutations which reduce cytotoxicity and complement activation to virtually undetectable levels.

The crystal structure of pneumococcal surface antigen PsaA reveals a metal-binding site and a novel structure for a putative ABC-type binding protein.

BACKGROUND: . The surface protein PsaA of the pathogenic bacterium Streptococcus pneumoniae plays an essential role in its virulence. PsaA is a putative ATP-binding cassette-type (ABC-type) binding protein involved in the uptake of Mn2+ and possibly Zn2+ and is considered to be both a potential drug target and and a candidate vaccine component. RESULTS: . The structure of PsaA has been determined to 2.0 A resolution using X-ray crystallography and is the first structure obtained for an ABC-type binding protein from a Gram-positive organism. The protein consists of two (beta/alpha)4 domains linked together by a single helix. A metal-binding site is formed in the domain interface by the sidechains of His67, His139, Glu205 and Asp280 and is occupied in the structure. CONCLUSIONS: . The structural topology of PsaA is fundamentally different from that of other ABC-type binding proteins determined thus far in that PsaA lacks the characteristic 'hinge peptides' involved in conformational change upon solute uptake and release. In our structure, the metal-binding site is probably occupied by Zn2+. The site seems to be well conserved amongst related receptors from both Gram-positive and Gram-negative bacteria.

The laryngeal mask airway in emergency medicine, neonatal resuscitation, and intensive care medicine.

In assessing the potential role of the LMA outside the operating room, the risks of a less secure airway must be balanced against the benefits of ease of training, success and speed of insertion, no need for direct visualization of laryngeal structures, and lesser need for ancillary equipment. The LMA has a role as an alternative to FMV in CPR when personnel skilled in tracheal intubation are not available. When skilled intubators are present, it has an important role as an alternative airway when intubation has been impossible. These roles extend to the prehospital setting, with an additional specific indication for its use when access to a patient is limited making tracheal intubation impossible. The LMA is incorporated into advanced life support training and as such should be regarded as a device providing temporary airway support, rather than a replacement for a tracheal tube. The LMA, and possibly also the ILM, should be standard equipment carried by prehospital trauma teams and by all those attending victims in the field.

An evaluation of the factors influencing selection of the optimal size of laryngeal mask airway in normal adults.

The purpose of this randomised single blinded study was to determine the optimal size of laryngeal mask airway in the normal adult population, to test the validity of the current selection criteria and to determine if any externally measured anatomical variable correlated with optimal size. In each of 30 apnoeic anaesthetised adults weighting less than 100 kg, size 3, 4 and 5 laryngeal mask airways were inserted in random order by a skilled user and the cuff inflated to a standard pressure (60 cm H2O). Optimal size was based on four criteria in order of priority: number of attempts at placement, oropharyngeal leak pressure, fiberoptic score and percentage of vocal cords seen. The size 5 laryngeal mask airway was optimal in 19/30 and the size 4 in 11/30. In no patient was the size 3 the optimal fit. Oropharyngeal leak pressure was significantly higher for each progressively large size and the fiberoptic view was significantly better for the size 4 and size 5. There was no significant predictive value in any externally measured anatomical variable, but height was the most useful. The best current selection strategy was to choose a size 5 for males and size 4 for females. Potentially useful new strategies may be to use the size 5 in all adults, or a size 5 > or = 165 cm in height and size 4 for < 165 cm. We conclude that predicting the optimal size of laryngeal mask airway for individual adult patients is complex. The best size selection strategies involve use of the size 4 and 5 laryngeal mask airways in adults.

A comparison of the laryngeal mask airway and cuffed oropharyngeal airway in anesthetized adult patients.

UNLABELLED: We compared the cuffed oropharyngeal airway (COPA) with the laryngeal mask airway (LMA) in 120 anesthetized adult patients. We compared 1) placement success rates, 2) airway interventional requirements, 3) airway stability in different head/neck positions, 4) cardiorespiratory tolerance, and 5) intra- and postoperative adverse events/symptoms. A standardized anesthesia protocol was followed by four anesthesiologists experienced with both devices. Observational data were validated by independent analysis of continuous video recordings. Postoperative interviews were double-blind to the device used. The LMA had a more frequent success rate than COPA (97% vs 55%, P < 0.00001), an overall higher success rate (100% vs 83%; P = 0.001), a shorter time to achieve an effective airway (49 vs 188 s; P < 0.00001), a higher oropharyngeal leak pressure (21 vs 16 cm H2O; P = 0.003), and a fewer number of chin lift airway interventions required (0.1% vs 42%; P < 0.00001). When comparing mean tidal volumes in different head/neck positions to assess airway stability, the quality of airway was unchanged in 98% patients with the LMA and 54% with the COPA (P < 0.00001). The incidences of intraoperative adverse events were similar. On removal, blood was detected more often on the COPA (3% vs 14%; P = 0.04). In the late postoperative period, more patients complained of adverse symptoms with the COPA than with the LMA (26% vs 57%; P = 0.001). Late postoperative symptoms occurred more frequently with the COPA (0.87 vs 0.34; P = 0.003). There was more late postoperative sore throat (14% vs 36%; P = 0.0003) and more jaw/neck pain (12% vs 26%; P = 0.0008) in patients managed with the COPA. This study demonstrates that the LMA offers advantages over the COPA in most technical aspects of airway management and in terms of postoperative morbidity. IMPLICATIONS: In this randomized, prospective study, we compared the laryngeal mask airway and the cuffed oropharyngeal airway in anesthetized patients. The laryngeal mask airway offers advantages in most technical aspects of airway management and in terms of postoperative morbidity.