Videolaryngoscopy versus direct laryngoscopy for adult patients requiring tracheal intubation: a Cochrane Systematic Review.

Difficulties with tracheal intubation commonly arise and impact patient safety. This systematic review evaluates whether videolaryngoscopes reduce intubation failure and complications compared with direct laryngoscopy in adults. We searched CENTRAL, MEDLINE, Embase and clinicaltrials.gov up to February 2015, and conducted forward and backward citation tracking. We included randomized controlled trials that compared adult patients undergoing laryngoscopy with videolaryngoscopy or Macintosh laryngoscopy. We did not primarily intend to compare individual videolaryngoscopes. Sixty-four studies (7044 participants) were included. Moderate quality evidence showed that videolaryngoscopy reduced failed intubations (Odds Ratio (OR) 0.35, 95% Confidence Interval (CI) 0.19-0.65) including in participants with anticipated difficult airways (OR 0.28, 95% CI 0.15-0.55). There was no evidence of reduction in hypoxia or mortality, but few studies reported these outcomes. Videolaryngoscopes reduced laryngeal/airway trauma (OR 0.68, 95% CI 0.48-0.96) and hoarseness (OR 0.57, 95% CI 0.36-0.88). Videolaryngoscopy increased easy laryngeal views (OR 6.77, 95% CI 4.17-10.98) and reduced difficult views (OR 0.18, 95% CI 0.13-0.27) and intubation difficulty, typically using an 'intubation difficulty score' (OR 7.13, 95% CI 3.12-16.31). Failed intubations were reduced with experienced operators (OR 0.32, 95% CI 0.13-0.75) but not with inexperienced users. We identified no difference in number of first attempts and incidence of sore throat. Heterogeneity around time for intubation data prevented meta-analysis. We found evidence of differential performance between different videolaryngoscope designs. Lack of data prevented analysis of impact of obesity or clinical location on failed intubation rates. Videolaryngoscopes may reduce the number of failed intubations, particularly among patients presenting with a difficult airway. They improve the glottic view and may reduce laryngeal/airway trauma. Currently, no evidence indicates that use of a videolaryngoscope reduces the number of intubation attempts or the incidence of hypoxia or respiratory complications, and no evidence indicates that use of a videolaryngoscope affects time required for intubation.

Sanatoria revisited: sunlight and health.

Since the 18th century tuberculosis has been a major cause of death throughout the world. It is a highly infectious disease that spreads by droplet infection and finding effective treatment to combat tuberculosis took a great deal of time. One of the first treatments to have some real success was a stay in a sanatorium. Sanatoria were homes that provided patients with good food and fresh air (and therefore sunlight). The first sanatorium to use sunlight therapy (heliotherapy) seriously was founded in Leysin, Switzerland, by Auguste Rollier. Patients built up their sun exposure gradually to prevent sunburn or skin damage. We suggest that heliotherapy was more successful in treating tuberculosis than was appreciated once chemotherapy became available. The birth of heliotherapy coincided with an increased appreciation of the association of sunlight and health among the general public. The secret of its success is the combined effects of sunlight on the skin inducing the production of nitric oxide and vitamin. Nitric oxide is not only a messenger in the cardiovascular system and responsible for relaxation of vascular muscle but is also involved in the innate immune system. Vitamin D is responsible for immune system functions and multiple studies have found an association between tuberculosis immunity and high vitamin D levels. Therefore, it is understandable that providing tuberculosis patients with sunlight may have boosted their immune system and aided them in the fight against tuberculosis. In view of the high level of resistance to all drug regimens in some patients, perhaps it is time to revive the use of sanatoria in the fight against tuberculosis.

Differential gene expression in the duodenum, jejunum and ileum among crossbred beef steers with divergent gain and feed intake phenotypes.

Small intestine mass and cellularity were previously associated with cattle feed efficiency. The small intestine is responsible for the digestion of nutrients and absorption of fatty acids, amino acids and carbohydrates, and it contributes to the overall feed efficiency of cattle. The objective of this study was to evaluate transcriptome differences among the small intestine from cattle with divergent gain and feed intake. Animals most divergent from the bivariate mean in each of the four phenotypic Cartesian quadrants for gain × intake were selected, and the transcriptomes of duodenum, jejunum and ileum were evaluated. Gene expression analyses were performed comparing high gain vs. low gain animals, high intake vs. low intake animals and each of the phenotypic quadrants to all other groups. Genes differentially expressed within the high gain-low intake and low gain-high intake groups of animals included those involved in immune function and inflammation in all small intestine sections. The high gain-high intake group differed from the high gain-low intake group by immune response genes in all sections of the small intestine. In all sections of small intestine, animals with low gain-low intake displayed greater abundance of heat-shock genes compared to other groups. Several over-represented pathways were identified. These include the antigen-processing/presentation pathway in high gain animals and PPAR signaling, starch/sucrose metabolism, retinol metabolism and melatonin degradation pathways in the high intake animals. Genes with functions in immune response, inflammation, stress response, influenza pathogenesis and melatonin degradation pathways may have a relationship with gain and intake in beef steers.

Nineteenth century exercise clinics for the treatment of scoliosis.

Scoliosis is the abnormal lateral curvature and rotation of the spine. In the past this deformity has been linked with moral depravity, as in the case of Richard III. Treatment for scoliosis began with Hippocrates's use of boards and axial distortion. Today, bracing and surgery are used either to correct the deformity or to prevent further progression. In the past, however, exercise regimens have been used in the belief that strengthening back muscles would reduce curvature progression. This approach was pioneered by Per Henrik Ling in the early nineteenth century and was continued by his followers Mathius Roth and Franz Berwald and, most notably, by Gustav Zander. Even today a few clinics, particularly in Eastern Europe, still use exercise in the treatment of scoliosis. Whether it is effective remains debatable, but even if progression is not prevented the patient's general health will benefit from an exercise regimen.

Laparoscopic hernia complexity predicts operative time and length of stay.

PURPOSE: Laparoscopic ventral hernia repair (LVHR) is associated with shorter hospitalization and lower complication rates compared to open ventral hernia repair. We sought to determine if hernia-related factors, such as defect size and re-operative status correlate with postoperative complications, operative times and length of stay (LOS). METHODS: The study is a retrospective review of 30-day perioperative outcomes following LVHR in 91 patients who underwent surgery at a single institution from August 2009 through June 2012. A single surgeon performed all procedures. RESULTS: Indications for surgery were recurrent incisional hernia in 33 % of patients and primary incisional or ventral abdominal hernias in the rest. Coated polyester mesh with an average size of 348 cm(2) (±214; range 113-1,036) was used. Mean operative time was 132 min (±66.1; range 53-412). The mean LOS was 4.0 days (±3.5; range 1-22). Complications occurred in 13 patients for overall morbidity of 16.5 % and no mortality. There was one recurrence in 30 days (1.1 %). Patients who had a surgery >120 min or a LOS >1 day were statistically more likely to have multiple hernias, larger defect sizes (>40 cm(2)), larger mesh sizes (>300 cm(2)) or a history of recurrent hernia (P < 0.05). No other clinical or demographic variable evaluated in this study correlated with operative time or LOS. CONCLUSIONS: LVHR is safe with a low incidence of perioperative complications. Patients with multiple, larger and recurrent hernias have longer operative times and LOS. This information can be used to guide preoperative planning for the patient, surgeon and treating institution.

The role of scurvy in Scott's return from the South Pole.

Scurvy, caused by lack of vitamin C, was a major problem for polar explorers. It may have contributed to the general ill-health of the members of Scott's polar party in 1912 but their deaths are more likely to have been caused by a combination of frostbite, malnutrition and hypothermia. Some have argued that Oates's war wound in particular suffered dehiscence caused by a lack of vitamin C, but there is little evidence to support this. At the time, many doctors in Britain overlooked the results of the experiments by Axel Holst and Theodor Frølich which showed the effects of nutritional deficiencies and continued to accept the view, championed by Sir Almroth Wright, that polar scurvy was due to ptomaine poisoning from tainted pemmican. Because of this, any advice given to Scott during his preparations would probably not have helped him minimise the effect of scurvy on the members of his party.

A brief history of malaria chemotherapy.

Malaria is one of the worst sicknesses to affect humankind. For centuries there was no specific treatment, and it was not until the seventeenth century that Spanish colonisers brought back from Peru tree bark from which quinine was later extracted. In the twentieth century, synthetic alternatives to quinine were developed. Of these, chloroquine was the most successful, but by the 1970s widespread resistance had developed and the world was left without an effective treatment for malaria. During the same decade Chinese scientists extracted from sweet wormwood plant the drug artemisinin, which has proved to be very effective against chloroquine-resistant malarial parasites. The use of a combination therapy including artemisinin has made it possible to contemplate the eradication of malaria. Efforts to produce a stable and inexpensive supply of artemisinin are under way.

Exploring Scotland's influenza pandemic of 1918-19: lest we forget.

The 1918-1919 influenza pandemic resulted in more deaths than any other medical event in human history; the most recent scholarship puts the death toll worldwide at 100 million. Scotland suffered a proportionate loss of life but it was little reported at the time and has been little studied by social historians since. The Great War had been such a traumatic experience that the authorities, and the general public, could take no more tragic news and the result was an uncanny silence. There is little information on the way in which people were affected by the pandemic. Such information could now be valuable as we plan a response to a pandemic of avian flu. This article aims to initiate study of an important episode in healthcare in Scotland.

'The heart less bounding': treating angina pectoris.

Although one group of drugs (including amyl nitrite and glyceryl tinitrate) has been used in the treatment of angina for over 100 years, the mode of action became clear only after the endothelium-derived relaxing factor had been identified as nitric oxide in 1987. Originally sodium nitrite was included in this group of drugs but it rapidly fell out of favour. Recently, however, interest in its therapeutic use has been revived. The medical uses of saltpetre (potassium nitrate) may be due to the presence of nitrite as an impurity.

Expression of tylM genes during tylosin production: phantom promoters and enigmatic translational coupling motifs.

In the genome of Streptomyces fradiae, the three tylM genes are codirectional with the upstream gene, tylGV. Although the introduction of transcriptional blocks into the tylM genes revealed that they are normally cotranscribed, expression of tylMI still persisted (albeit at a very low level) when either of the upstream genes, tylMII or tylMIII, was disrupted. Such expression apparently resulted from transcriptional initiation at spurious sites that probably contribute insignificantly, if at all, to promote activity in the wild type. Prior to the onset of tylosin production, tylMIII is transcribed independently of tylGV from an authentic promoter buried within tylGV. This latter observation is interesting given that the TGA stop codon of tylGV overlaps the GTG start codon of tylMIII. Evidently, terminally overlapping genes are not always translationally coupled.

ALA and ALA hexyl ester-induced porphyrin synthesis in chemically induced skin tumours: the role of different vehicles on improving photosensitization.

Exogenous administration of 5-aminolevulinic acid (ALA) is becoming widely used to enhance the endogenous synthesis of Protoporphyrin IX (PpIX) in photodynamic therapy. We analysed porphyrin formation in chemically induced squamous papillomas, after topical application of ALA and ALA hexyl ester (He-ALA) administered in different formulations, as well as the pattern of distribution in the internal organs, and the synthesis of porphyrins in distant tumoural and normal skins. A lotion formulation containing DMSO and ethanol was the best vehicle for topical ALA delivery to papillomas, whereas cream was the most efficient formulation for He-ALA application. Similar porphyrin concentration can be accumulated in the skin tumours employing either ALA or He-ALA delivered in their optimal formulations. The use of cream as a vehicle of both ALA and He-ALA, induces highest porphyrin tumour/normal skin ratios. The main advantage of using He-ALA is that porphyrins synthesized from the ester are more confined to the site of application, thus inducing low porphyrin levels in normal skin, liver, blood and spleen, as well as in papillomas distant from the point of application, independently on the vehicle employed, so reducing potential side effects of photodynamic therapy.

Influence of ancillary genes, encoding aspects of methionine metabolism, on tylosin biosynthesis in Streptomyces fradiae.

The tylosin-biosynthetic (tyl) gene cluster of Streptomyces fradiae contains ancillary genes that encode functions normally associated with primary metabolism. These can be disrupted without loss of viability, since equivalent genes (presumably used for 'housekeeping' purposes) are also present elsewhere in the genome. The tyl cluster also contains two genes that encode products unlike any proteins in the databases. Two ancillary genes, metF (encoding N5,N10-methylenetetrahydrofolate reductase) and metK, encoding S-adenosylmethionine synthase, flank one of the 'unknown' genes (orf9) in the tyl cluster. In a strain of S. fradiae in which all three of these genes were disrupted, tylosin production was reduced, although this effect was obscured in media supplemented with glycine betaine which can donate methyl groups to the tetrahydrofolate pool. Apparently, one consequence of the recruitment of ancillary genes into the tyl cluster is enhanced capacity for transmethylation during secondary metabolism.

Influence of dimethylsulfoxide on tylosin production in Streptomyces fradiae.

The polyketide aglycone, tylactone (protylonolide), does not normally accumulate during tylosin production in Streptomyces fradiae, suggesting that the capacity of the organism to glycosylate tylactone exceeds the capacity for polyketide synthesis. Consistent with this model, tylosin yields were significantly increased (due to bioconversion of the added material) when exogenous tylactone was added to fermentations. However, tylosin yield improvements were also observed (albeit at lower levels) in solvent controls to which dimethylsulfoxide (DMSO) was added. At least in part, the latter effect resulted from stimulation of polyketide metabolism by DMSO. This was revealed when the solvent was added to fermentations containing the tylA mutant, S. fradiae GS14, which normally accumulates copious quantities of tylactone.

Sit4p protein phosphatase is required for sensitivity of Saccharomyces cerevisiae to Kluyveromyces lactis zymocin.

We have identified two Saccharomyces cerevisiae genes that, in high copy, confer resistance to Kluyveromyces lactis zymocin, an inhibitor that blocks cells in the G(1) phase of the cell cycle prior to budding and DNA replication. One gene (GRX3) encodes a glutaredoxin and is likely to act at the level of zymocin entry into sensitive cells, while the other encodes Sap155p, one of a family of four related proteins that function positively and interdependently with the Sit4p protein phosphatase. Increased SAP155 dosage protects cells by influencing the sensitivity of the intracellular target and is unique among the four SAP genes in conferring zymocin resistance in high copy, but is antagonized by high-copy SAP185 or SAP190. Since cells lacking SIT4 or deleted for both SAP185 and SAP190 are also zymocin resistant, our data support a model whereby high-copy SAP155 promotes resistance by competition with the endogenous levels of SAP185 and SAP190 expression. Zymocin sensitivity therefore requires a Sap185p/Sap190p-dependent function of Sit4p protein phosphatase. Mutations affecting the RNA polymerase II Elongator complex also confer K. lactis zymocin resistance. Since sit4Delta and SAP-deficient strains share in common several other phenotypes associated with Elongator mutants, Elongator function may be a Sit4p-dependent process.

Direct NO group transfer from S-nitrosothiols to iron centres.

A number of S-nitrosothiols react rapidly with the Fe(II) complexes of 2,3-dimercapto-1-propanesulfonic acid (DMPS) and of N-methyl-D-glucamine dithiocarbamate (MGD), transferring the NO group directly to the iron centres.

Inhibition of human platelet aggregation by a novel S-nitrosothiol is abolished by haemoglobin and red blood cells in vitro: implications for anti-thrombotic therapy.

1. S-Nitrosothiols are nitric oxide (NO) donor drugs that have been shown to inhibit platelet aggregation in platelet rich plasma (PRP) in vitro and to inhibit platelet activation in vivo. The aim of this study was to compare the platelet effects of a novel S-nitrosated glyco-amino acid, RIG200, with an established S-nitrosothiol, S-nitrosoglutathione (GSNO) in PRP, and to investigate the effects of cell-free haemoglobin and red blood cells on S-nitrosothiol-mediated inhibition of platelet aggregation. 2. The effects of GSNO and RIG200 in collagen (2.5 microg ml(-1))-induced platelet aggregation in PRP and whole blood were investigated in vitro. Both compounds were found to be powerful inhibitors of aggregation in PRP, and RIG200 was significantly more potent (IC(50)=2.0 microM for GSNO and 0.8 microM for RIG200; P=0.04). 3. Neither compound inhibited aggregation in whole blood, even at concentrations of 100 microM. Red blood cell concentrations as low as 1% of the haematocrit, and cell-free haemoglobin (> or = 2.5 microM), significantly reduced their inhibitory effects on platelets. 4. Experiments involving measurement of cyclic GMP levels, electrochemical detection of NO and electron paramagnetic resonance of haemoglobin in red blood cells, indicated that scavenging of NO generated from S-nitrosothiols by haemoglobin was responsible for the lack of effect of S-nitrosothiols on platelets in whole blood. 5. These studies suggest that scavenging of NO by haemoglobin in blood might limit the therapeutic application of S-nitrosothiols as anti-platelet agents.

Novel S-nitrosothiols do not engender vascular tolerance and remain effective in glyceryltrinitrate-tolerant rat femoral arteries.

Organic nitrates, such as glyceryltrinitrate, are nitric oxide (NO) donor drugs that engender tolerance with long-term use. Here, we tested the hypothesis that our novel S-nitrosothiols, N-(S-nitroso-N-acetylpenicillamine)-2-amino-2-deoxy-1,3,4,6, tetra-O-acetyl-beta-D-glucopyranose (RIG200) and S-nitroso-N-valeryl-D-penicillamine (D-SNVP), do not induce vascular tolerance ex vivo. Femoral arteries from adult male Wistar rats were preconstricted with phenylephrine and perfused with the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME). Perfusion pressure was measured during 20 h treatment with supramaximal concentrations of NO donor (10 microM). Perfusion with glyceryltrinitrate caused a vasodilatation, which recovered over 2-20 h. In contrast, the S-nitrosothiols caused vasodilatations that were maintained throughout the 20 h perfusion period. Responses to S-nitrosothiols were partially reversed by the NO scavenger ferrohaemoglobin and fully reversed by the soluble guanylate cyclase inhibitor [1H-[1,2,4] oxadiazole [4,3-a]quinoxaline-1-one (ODQ). Glyceryltrinitrate-tolerant vessels were fully responsive to bolus injections of S-nitrosothiols. Resistance to tolerance is an attractive property of our novel compounds, particularly in view of their sustained activity in arteries with damaged endothelium.

Application of chemically induced dynamic nuclear polarization to the nitration of N-acetyltyrosine and to some reactions of peroxynitrite.

By the observation of chemically induced dynamic nuclear polarization in (15)N NMR spectroscopy it has been shown that nitration of N-acetyltyrosine, even under acidic conditions, is largely a radical process. In the alkaline reaction of tyrosine with peroxynitrite the main products are nitrite and nitrate, both produced by a radical pathway, and tyrosine nitration is a minor reaction. It is suggested that tyrosine catalyzes the production of NO(*)(2) and HO(*) from peroxynitrite.