Comparison of different methods of ventilation via cannula cricothyroidotomy in a trachea-lung model.

BACKGROUND: Cannula cricothyroidotomy is recommended in recent guidelines as a rescue intervention in the 'cannot-intubate cannot-ventilate' scenario. Several methods of providing ventilation via a cannula cricothyroidotomy have been described, but there are no data comparing these methods and using cannulae of differing diameters. METHODS: Using a bench-top trachea-lung model (comprising a Siemens test lung attached to commercially available breathing system tubing), we compared delivered minute volumes (MVs) for five methods of ventilation administered through cannulae of diameters 20, 16, 14, and 13 G. The ventilation methods were: an ENK oxygen flow modulator, a Manujet, a self-inflating resuscitation bag, the oxygen flush of an anaesthetic machine, and oxygen from a wall-mounted flow meter attached via a three-way tap to the cannula. All experiments were performed with and without a proximal 2.5 mm diameter constriction to simulate partial upper airway obstruction. RESULTS: MVs increased with increasing cannula diameter. In the absence of a proximal constriction, MVs delivered via a 20 G cannula were <1 litre min(-1) with all devices; only the Manujet delivered MVs >2 litre min(-1), at cannula sizes of >or=16 G. MVs were greater in the presence of a proximal constriction, but did not exceed 4 litre min(-1) using the low-pressure devices. CONCLUSIONS: Extrapolated to the clinical situation, these data suggest that low-pressure devices will not deliver adequate MVs via a cannula cricothroidotomy and should no longer be advocated. Purpose-made devices should be available in all areas where anaesthesia is administered or airway interventions are performed.

Adenoviruses: update on structure and function.

Adenoviruses have been studied intensively for over 50 years as models of virus-cell interactions and latterly as gene vectors. With the advent of more sophisticated structural analysis techniques the disposition of most of the 13 structural proteins have been defined to a reasonable level. This review seeks to describe the functional properties of these proteins and shows that they all have a part to play in deciding the outcome of an infection and act at every level of the virus's path through the host cell. They are primarily involved in the induction of the different arms of the immune system and a better understanding of their overall properties should lead to more effective ways of combating virus infections.

Air entrainment during high-frequency jet ventilation in a model of upper tracheal stenosis.

BACKGROUND: Previous work has demonstrated that when high-frequency jet ventilation (HFJV) is applied above an airway stenosis, higher distal airway pressures are produced compared with when the same ventilation is delivered below the stenosis (BSV). This study aimed to investigate the mechanisms underlying this finding. METHODS: HFJV was applied to a model of laryngo-tracheal stenosis with the jet located above the stenosis (ASV), with a catheter passed through the stenosis (TSV) or with HFJV delivered by a side port BSV. For each configuration and over a range of diameters of stenosis (2.5-8.5 mm), distal tracheal pressures and delivered minute volume were measured and air entrainment estimated. Experiments were repeated using the same model with the addition of a simulated 'pharynx' around the stenosis. RESULTS: Distal airway pressures, minute volumes, and air entrainment were consistently higher during ASV compared with BSV and TSV. The presence of the 'pharynx' made no significant difference to airway pressures or air entrainment. Delivered minute volumes varied between ASV, TSV, and BSV, and were also dependent on the stenosis diameter. With ASV, there appeared to be a range of stenosis diameters (4.0-5.5 mm) which 'maximized' minute volumes. CONCLUSIONS: The results suggest that the high airway pressures generated during ASV are the consequence of air entrainment and this effect, although reduced slightly, is maintained in the presence of the model pharynx. In contrast to the previous work, no significant entrainment occurred during BSV. If applicable to patients, these data suggest that ASV HFJV should be avoided in small diameter stenoses, but provides more efficient gas delivery and greater distending pressures with larger stenoses. BSV HFJV produces lower distal pressures and more consistent oxygen concentrations of injected gas across a range of stenosis diameters.

Effects of helium on high frequency jet ventilation in model of airway stenosis.

BACKGROUND: The addition of helium to the inspired gas may facilitate ventilation in the presence of clinically evident upper airway obstruction. However, there are no data on the effects of using a helium-oxygen mixture during high frequency jet ventilation (HFJV) in upper airway obstruction. METHODS: HFJV at a frequency of 150 min(-1) (driving pressure 2 bar, inspiratory time 30%) was applied to a trachea-lung model to simulate ventilation through varying degrees of fixed laryngotracheal stenosis (2.5-8.5 mm). HFJV was delivered from above, through and below the level of stenosis to simulate supraglottic, transglottic and infraglottic administration. Measurements of distal tracheal pressures were repeated for each route at steady state for each stenosis diameter using both 100% oxygen and helium-oxygen (50% oxygen, 50% helium). The output of the ventilator was measured during operation on oxygen and helium-oxygen. RESULTS: Peak, mean and end-expiratory pressures were greater during simulated supraglottic HFJV than during transglottic and infraglottic HFJV, and pressures increased markedly as the diameter of the stenosis decreased for all routes of ventilation (P<0.001). Generated pressures during HFJV using helium-oxygen and 100% oxygen were very similar overall, although reductions in pressures were observed during ventilation with helium-oxygen via the transglottic and transtracheal routes at stenosis diameters <4 mm (P<0.05). However, HFJV with the helium-oxygen mixture increased the delivered gas volumes by approximately 18%. CONCLUSIONS: Using 50% helium-oxygen during HFJV in the presence of airway stenosis allows an 18% increase in minute volume at generated airway pressures which are the same as or lower than those when using 100% oxygen.

The incidence of genotypes at codon 171 of the prion protein gene (PRNP) in five breeds of sheep and production traits of ewes associated with those genotypes.

Scrapie is one of several transmissible spongiform encephalopathies of livestock. Disease susceptibility is linked to polymorphisms in the normal prion protein gene that encodes the mammalian prion precursor. Codon 171 of this gene is a major determinant of scrapie susceptibility. Selection for arginine (R) at codon 171 is encouraged by the USDA to decrease the incidence of scrapie. Objectives of this study were to determine the frequency of R allele variants at codon 171 in a sample of sheep from five breeds (Columbia, Hampshire, Rambouillet, Suffolk, and Targhee) and western white-faced commercial ewes and to determine whether the R allele is associated with ewe and lamb production traits. Genotyping was performed on 532 ewes and 901 lambs from the University of Wyoming flock, in addition to 820 rams from 52 sheep producers from Wyoming and surrounding areas, using a DNA mismatch assay that discriminated the R allele from others at codon 171. Genotyping was performed by DNA sequencing on 127 rams representing all breeds, except Hampshire from the USDA Sheep Experiment Station at Dubois, ID. The 171R allele was found in all five breeds and in the commercial western white-faced ewes. Genotype frequencies varied (P < 0.001) by breed in ewe and ram populations. Influence of R-allele frequency on ewe lambing records and individual lamb records was analyzed for Columbia (62, 161, 121), Hampshire (89, 193, 162), Rambouillet (87, 179, 133), Suffolk (67, 178, 161), and commercial sheep (227, 463, 324) for numbers of ewes, total number of ewe production records, and individual lamb records, respectively. Suffolk ewes without the R allele (non-R/non-R) gave birth to more (P or= 0.08) by ewe genotype. Lamb birth and weaning weights were not influenced (P >or= 0.12) by lamb genotype in any of the breeds or in the commercial flock. In this population, ultimate lamb production was only influenced by genotype at codon 171 in the Suffolk flock.

Nuclear perturbations following adenovirus infection.

Adenoviruses are processed and assembled in the nuclei of infected cells and thereby produce significant perturbations to their structure and function. As the complex interactions that occur in the nuclei of uninfected cells are not yet fully understood many of the changes seen on infection have been described mainly in morphological terms. This chapter attempts to place more recent findings into this context and demonstrates that adenoviruses are able to hijack many cellular processes and enzymes to their advantage. In particular, modifications to nuclear PODs and nucleoli have more recently been explored in greater detail.

Complete airway obstruction in a ventilated patient after oesophageal dilatation.

A case of instrumental perforation of the oesophagus is presented. This caused systemic sepsis, requiring tracheal intubation and positive pressure ventilation. Sudden unexpected life-threatening airway obstruction was caused by distal tracheal compression by a peritracheal abscess. The aetiology and management of distal tracheal obstruction is discussed.

Comparison of external jugular and central venous pressures in mechanically ventilated patient.

We compared central venous pressures, measured via a 150 mm triple lumen catheter in the internal jugular vein with simultaneous external jugular venous pressures, measured with a 5 mm cannula in the external jugular vein, in 24 patients undergoing major surgery. Patients were mechanically ventilated in the supine position. Six sets of paired measurements of mean central venous pressure and mean external jugular venous pressure were taken by a blinded observer, in random order and at end-expiration at 30-min intervals during surgery. Four patients were not studied because of a failure to cannulate the external jugular vein. The remaining 20 patients yielded 111 sets of paired measurements. The mean difference between external jugular venous pressure and central venous pressure was 0.3 mmHg over a range of central venous pressure of 0-22 mmHg. Limits of agreement were 3.6 to +3.0 mmHg (95% CI 4.1 to +3.5 mmHg). We conclude that external jugular venous pressure is an accurate estimate of central venous pressure in surgical patients undergoing mechanical ventilation.

The effect of neuromuscular blockade on oxygen supply, consumption, and total chest compliance in patients with high oxygen requirements undergoing mechanical ventilation.

We investigated the effects of neuromuscular blockade with atracurium on oxygen consumption, oxygen delivery and total chest compliance in 20 sedated intensive care patients who required mechanical ventilation with an inspired oxygen fraction of at least 0.6. The reverse Fick method was used to measure oxygen consumption. Total chest compliance was measured from the ventilator pneumotachograph and pressure transducer. Measurements were made before neuromuscular blockade, at a standard level of neuromuscular blockade, and after demonstrated recovery of neuromuscular function. There was no statistical difference in any of the parameters measured. However there were large changes in oxygen consumption (range -35% to +17%) and total chest compliance (range -19.7% to +9.7%) in individuals. We conclude that in the setting of critical oxygenation, neuromuscular blockade cannot be assumed to reduce oxygen requirements or improve total lung compliance. If, however, neuromuscular blockade is selected as an adjunct to therapy, we recommend that the indices of oxygenation are calculated.

Hepatic failure and hemochromatosis of Salers and Salers-cross cattle.

Hemochromatosis is rare in domestic mammals. Five clinical cases and one preclinical case of hemochromatosis were diagnosed in Salers and Salers-cross cattle. Clinical disease developed between 9 and 22 months of age. Animals were healthy until weaning but then lost weight, developed rough hair coats, and lost incisor teeth. In two animals, hemochromatosis was identified by liver biopsy, biochemical evidence of hepatic injury, and/or elevated transferrin saturation values. At necropsy, carcasses were thin, with firm dark brown livers and lymph nodes, soft bones, and brown-colored small bowel. The principal histologic changes were hepatocellular siderosis and periportal, bridging, and perivenular fibrosis. Siderocalcinosis involved collagen, elastin, reticulin, and basement membrane components in liver, lymph nodes, spleen, duodenum, and kidney. Hepatic iron concentrations in clinically affected cattle were 1,500-10,500 microg/g wet weight (reference range for cattle = <300 microg/ g). Ultrastructurally, the heaviest intrahepatic deposition was in hepatocytes, which contained large intracytoplasmic siderosomes. Iron deposition in bone was associated with osteopenia. Genetic analysis indicated a common ancestral bull in the pedigrees of five of six affected cattle; no pedigree was available for the remaining animal. Four dams of five affected animals were phenotypically normal and had histologically normal livers. Test mating of four cows to the ancestral bull resulted in a female calf that developed clinicopathologic and histologic evidence of preclinical hemochromatosis by 40 days of age. It was not possible to establish the pattern of inheritance because of the small number of pedigrees from affected cattle.

Mitochondrial protein p32 can accumulate in the nucleus.

Human p32 was first isolated associated with the splicing factor ASF/SF-2. The p32 protein is translated as pre-protein from which a mitochondrial import signal is cleaved off to create the mature p32. The majority of p32 is consequently found in the mitochondria. In this study we investigated extramitochondrial p32. An increased nuclear localisation of endogenous p32 was demonstrated as a response to leptomycin B or actinomycin D treatment of cells. Mature p32 gene and deletion mutants were cloned into enhanced green fluorescence protein reporter plasmids. On transfection, EGFP-p32 protein was mainly localised to the cytoplasm and to a lesser extent to the nucleus of transfected COS cells. Upon treatment with actinomycin D or leptomycin B, the EGFP-p32 protein accumulated in the nucleus. Deletion analysis indicated which regions of EGFP-p32 are involved in nuclear export and nuclear import.

The comfort of breathing: a study with volunteers assessing the influence of various modes of assisted ventilation.

OBJECTIVE: To assess the subjective feeling of comfort of healthy volunteers breathing on various modes of ventilation used in intensive care. DESIGN: A randomized, prospective, double-blinded, crossover trial using volunteers. SETTING: An intensive care unit (ICU) in a teaching hospital. INTERVENTIONS: We compared, by using healthy volunteers, the subjective feeling of comfort of three modes of ventilation used during the weaning phase of critical illness. We used healthy volunteers to avoid other distracting influences of intensive care that may confound the primary feeling of comfort. The modes we compared were synchronized intermittent mandatory ventilation, assisted spontaneous breathing, and biphasic positive airway pressure. The imposed ventilation was comparable with 50% of the volunteers' normal respiratory effort. The volunteers breathed via a mouthpiece through a ventilator circuit, and the modes of ventilation were introduced in a randomized manner. MEASUREMENTS AND MAIN RESULTS: We measured visual analog scores for comfort for the three modes of ventilation and collected a ranking order and open-ended comments. We demonstrated that at the level of support we imposed, assisted spontaneous breathing was the most comfortable mode of ventilation and that synchronized intermittent mandatory ventilation was the most uncomfortable. These results were strongly supported by both the ranking scale and comments of the volunteers. CONCLUSIONS: Assisted spontaneous breathing was the most comfortable mode of ventilation because the pattern was primarily determined by the volunteer. Synchronized intermittent mandatory ventilation was the most uncomfortable because the ventilatory pattern was imposed on the volunteers, leading to ventilator-volunteer dyssynchrony. We also conclude there is wide individual variation in the subjective feeling of comfort. Whereas the mode of ventilation in ICUs is based primarily on the physiologic needs of the patient, the feeling of comfort may be considered when choosing an appropriate mode of ventilation during the weaning phase of critical illness.

Interaction between herpes simplex virus type 1 IE63 protein and cellular protein p32.

The herpes simplex virus type 1 (HSV-1) immediate-early gene IE63 (ICP27), the only HSV-1 regulatory gene with a homologue in every mammalian and avian herpesvirus sequenced so far, is a multifunctional protein which regulates transcriptional and posttranscriptional processes. One of its posttranscriptional effects is the inhibition of splicing of viral and cellular transcripts. We previously identified heterogeneous nuclear ribonucleoprotein (hnRNP) K and casein kinase 2 (CK2) as two protein partners of IE63 (H. Bryant et al., J. Biol. Chem. 274:28991-28998, 1999). Here, using a yeast two-hybrid assay, we identify another partner of IE63, the cellular protein p32. Confirmation of this interaction was provided by coimmunoprecipitation from virus-infected cells and recombinant p32 binding assays. A p32-hnRNP K-CK2 complex, which required IE63 to form, was isolated from HSV-1-infected cells, and coimmunoprecipitating p32 was phosphorylated by CK2. Expression of IE63 altered the cytoplasmic distribution of p32, with some now colocalizing with IE63 in the nuclei of infected and transfected cells. As p32 copurifies with splicing factors and can inhibit splicing, we propose that IE63 together with p32, possibly with other IE63 partner proteins, acts to disrupt or regulate pre-mRNA splicing. As well as contributing to host cell shutoff, this effect could facilitate splicing-independent nuclear export of viral transcripts.

An epitope on the adenovirus fibre tail is common to all human subgroups.

A group specific linear epitope with the sequence -FNPVY- was detected in the tail region of the adenovirus fibre by using a monoclonal antibody (Mab) and selection with a hexapeptide phage expression library. A synthetic peptide with sequence DTFNPVYPYDTE from adenovirus type 2 (Ad2) was shown by preincubation with the Mab to block its binding to fibre. A biotinylated form of this peptide bound to the monomeric fibre and not to the dimeric and trimeric forms. On the other hand the monoclonal antibodies bound to the monomeric, dimeric and trimeric forms of the fibre.

Cricothyroidotomy and transtracheal high frequency jet ventilation for elective laryngeal surgery. An audit of 90 cases.

We carried out an audit of needle cricothyroidotomy and transtracheal ventilation used during anaesthesia for elective endolaryngeal surgery. The data on 90 consecutive procedures was collected over two years. Patients were anaesthetized using a total intravenous technique. An intravenous cannula or Tuohy needle was placed through the cricothyroid membrane and the patient was ventilated via the cannula using high frequency jet ventilation. Technical details of the procedure and any perioperative complications were recorded. There were 12 complications in total. Only three of these were clearly related to the cricothyroid puncture, i.e., one minor bleed and two cases of limited local surgical emphysema. All complications were minor and resolved without sequelae.