Abnormal vascular network complexity: a new phenotypic marker in hereditary non-polyposis colorectal cancer syndrome.

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) (Lynch cancer family syndrome I (LCFS1) and II (LCFS2)) is one of the most common hereditary cancer disorders. HNPCC results from dominantly inherited germline mutations in mismatch repair (MMR) genes, leading to genomic instability and cancer. No predictive physical signs of HNPCC are available to date. AIMS: Increased complexity in tumour associated vascular growth has been reported. Here, we tested the hypothesis that an increased vascular network complexity is a phenotypic marker for LCFS2. METHODS: Fourteen subjects from an LCFS2 kindred (gene carriers, n=5; non-carriers, n=9) and 30 controls were examined. Fractal dimension (D) at two scales (D (1-46), and D (1-15), tortuosity (minimum path dimension, Dmin), and relative Lempel-Ziev complexity (L-Z) of the vascular networks from the lower gingival and vestibular oral mucosa were measured. RESULTS: LCFS2 networks exhibited a significantly increased overall complexity at both larger (D (1-46): 1.82 (0.04) v 1.68 (0.08); p<0.0001) and smaller (D (1-15): 1.51 (0.11) v 1.20 (0.09); p<0.0001) scales, increased destructured randomness (L-Z: 0.77 (0.09) v 0.56 (0.03); p<0.0001), and decreased vessel tortuosity (DMIN: 1.02 (0.03) v 1.07 (0.04); p=0.0005) compared with control patterns. The vascular networks of LCFS2 gene carriers showed higher complexity at the smaller scale (D (1-15): 1.59 (0.12) v 1.47 (0.07); p=0.034), and higher destructured randomness (L-Z: 0.85 (0.11) v 0.73 (0.05); p=0.013) than those of non-carriers. CONCLUSIONS: Increased oral vascular network complexity is a previously unrecognised phenotypic marker for LCFS2, and is related to gene mutation carrier status.

Masimo signal extraction pulse oximetry.

OBJECTIVE: To describe a new pulse oximetry technology and measurement paradigm developed by Masimo Corporation. INTRODUCTION: Patient motion, poor tissue perfusion, excessive ambient light, and electrosurgical unit interference reduce conventional pulse oximeter (CPO) measurement integrity. Patient motion frequently generates erroneous pulse oximetry values for saturation and pulse rate. Motion-induced measurement error is due in part to widespread implementation of a theoretical pulse oximetry model which assumes that arterial blood is the only light-absorbing pulsatile component in the optical path. METHODS: Masimo Signal Extraction Technology (SET) pulse oximetry begins with conventional red and infrared photoplethysmographic signals, and then employs a constellation of advanced techniques including radiofrequency and light-shielded optical sensors, digital signal processing, and adaptive filtration, to measure SpO2 accurately during challenging clinical conditions. In contrast to CPO which calculates O2 saturation from the ratio of transmitted pulsatile red and infrared light, Masimo SET pulse oximetry uses a new conceptual model of light absorption for pulse oximetry and employs the discrete saturation transform (DST) to isolate individual "saturation components" in the optical pathway. Typically, when the tissue under analysis is stationary, only the single saturation component produced by pulsatile arterial blood is present. In contrast, during patient motion, movement of non-arterial components (for example, venous blood) can be identified as additional saturation components (with a lower O2 saturation). When conditions of the Masimo model are met, the saturation component corresponding to the highest O2 saturation is reported by the instrument as SpO2. CONCLUSION: The technological strategies implemented in Masimo SET pulse oximetry effectively permit continuous monitoring of SpO2 during challenging clinical conditions of motion and poor tissue perfusion.

Comparison of a new venous control device with a bladder box system for use in ECMO.

During extracorporeal membrane oxygenation (ECMO), forward pump flow must not be allowed to exceed the rate of blood drainage from the patient so that excessive negative pressure does not develop within the ECMO circuit or in the patient's right atrium. A distensible reservoir ("bladder") and mechanically actuated electronic switch ("bladder box"), has typically been used for this purpose. If the rate of blood flow from the patient to the pump is insufficient to support the perfusion rate desired and adjustments in volume status and catheter position do not increase blood drainage, the only recourse is to increase the siphon pressure by elevating the patient. At the author's institution, a novel venous control module (VCM), without a reservoir, that can provide increased venous drainage without elevating the patient is used. Using an in vitro model of neonatal ECMO, the authors' compared their VCM to a commercially available "bladder box" system. Pressures were monitored in a collapsible chamber inside a water bath (simulating the right atrium), at the gravitational high point of the ECMO circuit ("neck site") and at the low point of the circuit ("venous site") at flow rates of 100, 450, 900, and 1,300 cc/min. Pump shut-off characteristics for both systems were also measured with either sudden interruption of venous drainage ("cross-clamping") or restriction of venous inflow ("hypovolemia"). Under continuous flow conditions, higher flows could be achieved with the VCM. With acute venous catheter occlusion, instantaneous ("trough") pressures at the neck site were lower, and venous monitoring site pressures were higher with the bladder box system.(ABSTRACT TRUNCATED AT 250 WORDS)

High-frequency oscillatory ventilation combined with intermittent mandatory ventilation in critically ill neonates: 3 years of experience.

A heterogeneous group of 45 neonates with severe pulmonary disease and inadequate gas exchange on conventional intermittent mandatory ventilation (IMV) was treated with a high-frequency oscillator combined with an IMV (HFO-IMV) system (Emerson Airway Vibrator connected to a BABYBird 1 ventilator). The mean gestational age was 33 weeks (25.5-43) and mean birth weight 2.02 kg (0.66-4.24). Primary diagnoses included respiratory distress syndrome (RDS; 23), pneumonia (12), persistent fetal circulation (PFC; 6), diaphragmatic hernia/hypoplastic lungs (4). The IMV rate was reduced from 78 to 29 BPM (P less than or equal to 0.0005), while maintaining lower partial pressure of carbon dioxide (PaCO2) (P less than 0.005) and higher partial pressure of oxygen (PaO2) (P less than or equal to 0.0025). Active air leaks were present in 20 infants and these infants responded most favourably to HFO-IMV. HFO-IMV failed to improve ventilation in neonates with diaphragmatic hernia/hypoplastic lungs. Complications during HFO-IMV were increased pulmonary secretions (11), worsening or recurrence of pre-existing air leaks (11), or occurrence of new air leaks (10). In 4 patients death was related to major air leak complications. Twenty-four infants died, 18 of them of a respiratory cause. Twenty-one infants finally survived. We assembled a well-tolerated system to provide HFO-IMV and to successfully ventilate neonates with severe respiratory disease, who failed to respond to conventional IMV. Initiation of HFO-IMV earlier in the course of the disease in this type of infant may improve survival.

Effects of infant ventilator design on spontaneous breathing.

Study of the mechanical work of spontaneous breaths taken by eight infants attached to infant ventilators. Work was estimated from the volume displacement and pressure fluctuations of breathing during steady state mechanical ventilator conditions (i.e., stable peak or PEEP pressures). A broad difference existed between manufacturers of infant ventilators; a dramatic reduction was seen in work when attached to a demand as compared to a continuous flow device. Additionally, some change in work occurred, depending on the phase of the IMV cycle in which spontaneous breath was taken. Dynamic testing of ventilators can reveal differences in function.

A system for high-frequency oscillatory ventilation and intermittent mandatory ventilation in neonates.

We combined high-frequency oscillatory ventilation and intermittent mandatory ventilation, using a system composed of an Emerson airway vibrator, a Babybird 1 ventilator, and rate/pressure monitors. The Emerson device, a modified air compressor with rate controller, oscillated a small volume of gas at the airway. This device was coupled to the bird unit through a circuit of our design. Humidified fresh gas and pressure-relief valves were provided by the bird ventilator, and mean airway pressure was adjusted by its expiratory-limb venturi device or by the end-expiratory pressure control. The volume of gas delivered by the oscillator to various sites was measured with a plethysmograph tuned to high frequencies. At frequencies of 20 to 30 Hz, a 27-ml volume from the oscillator decreased to between 7 and 14 ml at the proximal airway, and to between 0.1 and 2.3 ml at the distal tip of the endotracheal tube. The magnitude of this decrease depended on the size of the endotracheal tube, the circuit resistance of the ventilator, oscillation frequency, and the position of the oscillator's expansion-chamber valve. We have used this system for over 3 yr to ventilate sick neonates safely and effectively.

Combined high-frequency oscillatory ventilation and intermittent mandatory ventilation in critically ill neonates.

Combined high-frequency oscillatory ventilation (HFOV) and intermittent mandatory ventilation (IMV) was used in 12 neonates with inadequate gas exchange with conventional IMV. Diagnoses included diaphragmatic hernia with hypoplastic lungs, pneumonia, persistent fetal circulation, and severe respiratory distress syndrome. In most patients there was severe air leak. Within 10 hours of beginning HFOV-IMV the mean arterial PCO2 fell from 60 +/- 5 (means +/- SEM) to 38 +/- 2 mm Hg (P less than 0.01) and the mean IMV rate was reduced from 96 +/- 8 to 17 +/- 4 breaths per minute (P less than 0.001). The mean arterial-alveolar oxygen tension ratio rose from 0.05 +/- 0.01 to 0.09 +/- 0.01 (P less than 0.005). Mean airway pressure in the trachea was reduced from 16 +/- 2 to 10 +/- 3 cm H2O (P less than 0.05). Four patients died, three of whom had diaphragmatic hernias with hypoplastic lungs. Five of the eight survivors had mild bronchopulmonary dysplasia requiring supplemental oxygen. These studies demonstrate that in some neonates with respiratory failure who fail to respond to conventional IMV, combined HFOV-IMV can be successful.

Airway pressure measurement during high frequency oscillatory ventilation.

We developed a method to measure accurately pressures at the airway opening (Pao) and in the trachea (Ptr) in neonates during high frequency oscillatory ventilation (HFOV) from 15-30 Hz. All component parts of the pressure-measuring system were tested as a unit against a reference transducer in a closed chamber in which sinusoidal pressure waves could be generated. The resulting waveforms were displayed on an oscilloscope and measured. Ptr was measured through the intramural lumen of a Hi-Lo jet tracheal tube (National Catheter Co., Argyle, NY) opening 1 cm above the distal tip. Pressure readings from uncorrected waveforms indicated a discrepancy between measured and actual pressures, as high as 100% at frequencies of 100 Hz. When the resonance of the system was damped with a CorrecTORR (Norton Health Care Products, Akron, OH), the ratio of test to reference transducer output was flat +/- 5% from 0-160 Hz for the Pao system and flat +/- 4% from 0-100 Hz for the Ptr system. Ptr system accuracy was verified in an excised rabbit lung and the systems were used clinically in neonatal HFOV. We conclude that Pao and Ptr can be measured accurately during HFOV by this method.