Dynamic airflow limitation after topical anaesthesia of the upper airway.

This prospective before-and-after observational study investigated the effect of upper airway anaesthesia on dynamic airflow. Six consenting ASA 1 adults, all authors of this study, underwent a series of spirometric measurements before and after topical anaesthesia of the upper airway using lignocaine. Peak inspiratory flow rate, forced inspiratory flow between 25% and 75% of the maximum inhaled volume, forced expiratory volume at 1 second, and forced vital capacity in the supine and sitting positions were measured. The measured inspiratory parameters were significantly reduced after lignocaine topical anaesthesia of the upper airway. Expiratory flow parameters were not affected. We conclude that topical anaesthesia of the upper airway leads to dynamic inspiratory airflow limitation.

Cables enhances cdk2 tyrosine 15 phosphorylation by Wee1, inhibits cell growth, and is lost in many human colon and squamous cancers.

Cyclin-dependent kinase 2 (cdk2) is a small serine/threonine kinase that regulates cell cycle progression. Cdk2 activity is tightly controlled by several mechanisms, including phosphorylation and dephosphorylation events. Cables is a recently described novel cdk-interacting protein. In proliferating cells, Cables was predominantly localized in the nucleus by cell fractionation and immunostaining. Expression of Cables in HeLa cells inhibited cell growth and colony formation. Cables enhanced cdk2 tyrosine 15 phosphorylation by the Wee1 protein kinase, an inhibitory phosphorylation, which led to decreased cdk2 kinase activity. The gene encoding Cables is located on human chromosome 18q11-12, a site that is frequently lost in squamous, colon, and pancreas cancers. We found that Cables was strongly expressed in normal human epithelial cells including squamous and glandular mucosa. Breast and pancreatic cancers show strong Cables expression; however, loss of Cables expression was found in approximately 50-60% of primary colon and head and neck cancer specimens. Lack of Cables expression was associated with loss of heterozygosity on chromosome 18q11. The data provide evidence for a Cables-mediated interplay between cdk2 and Wee1 that leads to inhibition of cell growth. Conversely, loss of Cables may cause uncontrolled cell growth and enhance tumor formation.

Absorption of lidocaine during aspiration anesthesia of the airway.

STUDY OBJECTIVE: To determine the optimal solution to use when anesthetizing the airway by aspiration of lidocaine. DESIGN: Randomized, double-blind clinical study. SETTING: University hospital. PATIENTS: 96 adult ASA physical status 1,II, and III patients, scheduled for diagnostic flexible bronchoscopy. INTERVENTIONS: Patients were randomized to receive one of 5 solutions of lidocaine: Group A (n = 16): 1% lidocaine, 0.2 mL. kg(-1); Group B (n = 16): 1.5% 0.2 mL. kg(-1); Group C (n = 32): 2% 0.2 mL. kg(-1); Group D (n = 16): 1% 0.3 mL. kg(-1), and Group E (n = 16): 2% 0.3 mL. kg(-1). Fiberoptic bronchoscopy was performed after the airway was anesthetized with this aspiration technique, using the assigned lidocaine solution. The scope was manipulated in the trachea to test for anesthesia. MEASUREMENTS AND MAIN RESULTS: Successful airway anesthesia was determined by tolerance to bronchoscopy without sustained coughing, and also by the number of lidocaine supplements, if any, that were given via the bronchoscope. Arterial plasma concentrations of lidocaine were measured in 33 patients from Groups C, D, and E. All solutions provided equally effective anesthesia of the airway. All patients tolerated endoscopy through the vocal cords, and 94 patients required no supplementary anesthesia, or only one dose of lidocaine, during bronchoscopy to the carina. The highest peak plasma concentrations of lidocaine were 5.02 and 6.28 microg. mL. No patient had signs of toxicity. CONCLUSIONS: This technique produced anesthesia of the airway to the carina, safely, suitable for awake intubation, in 94 of 95 patients. The use of 1% lidocaine, 0.2 to 0.3 mL. kg(-1), so that the volume is 10 to 20 mL, is recommended.

Regulation of vascular endothelial growth factor by the Wnt and K-ras pathways in colonic neoplasia.

Angiogenesis is not restricted to advanced stages of tumor development but is also observed in benign precursor lesions. Vascular endothelial growth factor (VEGF) is a key regulator of tumor angiogenesis, but the genetic mechanisms controlling its expression in premalignant lesions are poorly described. The Wnt signaling pathway, which is commonly mutated in benign colonic adenomas, was found to strongly up-regulate VEGF. A T-cell factor-4-binding element at -805 bp in the VEGF promoter is an important mediator of this effect. Signaling through the K-ras oncogene, also frequently mutated in benign colonic polyps, up-regulated VEGF in a phosphatidylinositol 3-kinase-dependent manner. Furthermore, K-ras activation appeared to enhance Wnt signaling, which suggests a unique interaction between these two pathways. These studies thus identify VEGF as a novel target of the Wnt pathway in early colonic neoplasia and serve to underscore the importance of angiogenesis in premalignant disease.

A pharmacokinetic model for factor VIII dosing during active haemorrhage in patients with haemophilia A.

A theoretical one-compartment pharmacokinetic model is described, the aim of which is to guide factor VIII replacement therapy in patients with haemophilia A suffering from significant and ongoing haemorrhage. Based on our calculations, plasma factor VIII concentrations can decrease at a rapid rate even with non-severe blood loss.

Gabapentin for the treatment and prophylaxis of cluster headache.

BACKGROUND AND OBJECTIVES: Cluster headache is an uncommon debilitating condition for which effective management remains a challenge. We describe the use of gabapentin in the treatment and prophylaxis of cluster headache in a patient who was refractory to other treatments. CASE REPORT: A 38-year-old man had a history of intermittent right-side headaches for 24 years, diagnosed as cluster headache. He received only partial relief from a range of conventional treatments. A trial with gabapentin 300 mg twice daily was tried and found to be effective in treatment and prophylaxis of his headaches. CONCLUSION: Gabapentin was effective in the treatment of a patient with cluster headache. Further investigation of gabapentin compared with conventional treatments and placebo is warranted.

"Apnea-volume" warning during normal ventilation of the lungs: an unusual leak in the Narkomed 4 Anesthesia System.

We report a case of an unusual breathing circuit leak in the Narkomed 4 Anesthesia System due to a loose retaining ring at the junction of the expiratory valve assembly and the Spiromed Respiratory Volume Monitor. In the presence of the leak, the monitor panel displayed the messages "apnea volume" and "minute volume low," yet the low airway pressure alarm was not triggered and other parameters and clinical signs pointed to normal ventilation of the lungs. These conflicting data led to some delay in localizing the leak. After conclusion of the case, we found that occult loosening of this ring without causing leaks large enough to fail the FDA generic or manufacturer-recommended leak checks can occur. We recommend checking the tightness of this ring during routine leak checks and after rotating the expiratory valve assembly during re-positioning of the anesthetic system.

Airway difficulties caused by improperly applied cricoid pressure.

Cricoid pressure, when properly applied, may prevent gastric regurgitation and may improve the view of laryngoscopy. When improperly applied, however, it can impede laryngoscopy and mask-ventilation. When faced with a "cannot intubate" or "cannot mask-ventilate" situation, clinicians should reevaluate the manner with which the assistant is applying cricoid pressure and must be prepared to adjust or even to release it.

Overexpression of cyclin D1 occurs frequently in human pancreatic endocrine tumors.

The molecular pathogenesis of human pancreatic endocrine tumors (PETs) is poorly understood. Three independent animal models have pointed to the pivotal role of the G1/S cell cycle transition in pancreatic endocrine cell proliferation. We thus hypothesized that the cell cycle regulator cyclin D1 may contribute to the pathogenesis of human PETs. Overexpression of cyclin D1 was identified in 43% of cases, and no correlation was observed with clinical phenotype. The novel observation of frequent overexpression of cyclin D1 suggests that this established oncogene may be implicated in the pathogenesis of human PETs. The absence of detectable alterations in cyclin D1 genomic structure suggests that the mechanism for its oncogenic activation in PETs may be transcriptional or posttranscriptional.

Diluted venous blood appears arterial: implications for central venous cannulation.

IMPLICATIONS: There is always a danger of arterial puncture during central venous access. One can usually identify an inadvertent arterial puncture when the aspirated blood is bright red. This sign is removed if one were to put saline in the aspirating syringe, as dusky venous blood turns bright red on dilution.

The sedative and electroencephalographic effects of regional anaesthesia.

We studied sedation scores, the processed electroencephalogram and mean arterial pressure pre-operatively in patients before and after spinal (n = 15) and lumbar epidural (n = 15) anaesthesia. We compared them with changes occurring over time in a control group (n = 15), using the responsiveness component of the Observer Assessment of Alertness and Sedation rating scale. The electroencephalographic variables studied were bispectral index, 95% spectral edge frequency, median frequency and the power distribution between frequency bands alpha, beta, theta and delta. No differences were detected within groups in sedation scores before and after intervention, or between groups at either stage. No between-group differences were detected in electroencephalographic variables. In the spinal group, spinal anaesthesia caused an increase in bispectral index, 95% spectral edge frequency, median frequency and beta frequencies, and a decrease in delta frequencies and mean arterial pressure. The increase in beta frequencies is similar to that seen in patients with low plasma concentrations of midazolam and may represent subclinical sedation.

Lung isolation for the prevention of air embolism in penetrating lung trauma. A case report.

PURPOSE: To illustrate a new airway and ventilatory management strategy for patients with unilateral penetrating lung injury. Emphasis is placed on avoiding positive pressure ventilation (PPV)-induced systemic air/gas embolism (SAE) through traumatic bronchiole-pulmonary venous fistulas. CLINICAL FEATURES: A 14-yr-old male, stabbed in the left chest, presented with hypovolemia, left hemopneumothorax, an equivocal acute abdomen, and no cardiac or neurological injury. In view of the risk of SAE, we did not ventilate the left lung until any fistulas, if present, had been excised. After pre-oxygenation, general anesthesia was induced and a left-sided double-lumen tube (DLT) was placed to allow right-lung ventilation. Bronchoscopy was performed. The surgeons performed a thorascopic wedge resection of the lacerated lingula. Upon completion of the repair, two-lung ventilation was instituted while the ECG, pulse oximetry, PETCO2, and blood pressure were monitored. Peak inflation pressure was increased slowly and was well tolerated up to 50 cm H2O. The patient's intravascular status was maintained normal. CONCLUSION: Patients with lung trauma are at risk of developing SAE when their lungs are ventilated with PPV. In a unilateral case, expectant non-ventilation of the injured lung until after repair is recommended.

A bougie improves the utility of the UpsherScope.

STUDY OBJECTIVE: To assess the alignment of the tube-guide and visual-guide channels of the UpsherScope and to evaluate methods to improve the success of tracheal intubation. DESIGN: In-vitro observation followed by clinical series. SETTING: Tertiary care, academic medical institution. PATIENTS: 56 surgical patients. MEASUREMENTS AND MAIN RESULTS: In an in-vitro study, cross-marked concentric circles were used as the target for the tracheal tube. It confirmed that the tube-guide channel of the UpsherScope directs the tip of the tracheal tube posteriorly and to the right of the visual field when the tube was loaded into the guide channel, according to the manufacturer's recommendations. Of five other methods used for maneuvering the tracheal tube to the target, use of a bougie within the lumen of the tube resulted in the highest success rate. When this method was assessed in a clinical setting, it was successful in directing the tracheal tube into the trachea of 95% of the patient population. Two failures were due to secretions obscuring the view, and one, to a broken bougie. CONCLUSIONS: There is a functional misalignment between the long axes of the tube-guide and visual-guide channels of the UpsherScope. Use of a bougie will minimize this potential problem.

Anesthesia of the airway by aspiration of lidocaine.

PURPOSE: Lidocaine instilled onto to the back of the tongue of a supine subject and aspirated has been reported to provide effective topical anesthesia of the airway. The purpose of this study was to observe endoscopically the fate of lidocaine so instilled and document the efficacy of anesthesia for awake fibreoptic intubation. METHODS: In Part I of the study, a fibreoptic bronchoscope was positioned in the pharynx of three volunteers lying supine and the route followed by tinted lidocaine solution instilled onto the back of the protruded tongue during mouth breathing was observed. In Part 2, the airway of 39 patients requiring awake fibreoptic intubation was anesthetized by having them gargle twice with 5 ml lidocaine 2%, followed by instillation of 0.2 ml-kg(-1) or 20 ml lidocaine 1.5% (whichever was less) onto the dorsum of their tongues as described above. The efficacy of anesthesia was scored by the patient reaction (coughing or gagging) to instrumentation in the pharynx, at the glottis, and in the trachea; to passage of the tracheal tube into the trachea; and to the presence of the tube in the trachea. RESULTS: Lidocaine instilled on to the back of the tongue was swallowed initially but ultimately pooled in the pharynx and was aspirated. In all patients the trachea was intubated without requiring supplemental lidocaine, and all but one patient tolerated the tracheal tube in situ. CONCLUSION: A combination of lidocaine gargles and lidocaine instilled on to the back of the tongue and aspirated provides effective anesthesia of the pharynx, larynx, and trachea for awake fibreoptic intubation.