Design and its application of the f(n)-zeta chart capable of direct readout of the highest frequency indicating the limit of obtaining distortion-free waveforms

We have already reported that the highest frequency (f(h)) could serve as an index for evaluating the fidelity of pressure waveform derived via a catheter manometer system and be read off by the f(n)-zeta chart. Fh is determined by the natural frequency (f(n)) and damping coefficient ( zeta ) in the frequency characteristics of the system. Inversely, f(h) determines two pairs of f(n) and zeta in the f(n)-zeta chart, one in the case of zeta < 0.7 and the another zeta > 0.7. Then, each pair of f(n) and zeta determines respectively the resonant frequency (f(r)) and its amplitude (Ar) ( zeta < 0.7), or the corner frequency (f(c)) and its amplitude (Ac) ( zeta > 0.7) in the frequency characteristics. Thus, the point (f(r), Ar) or (f(c), Ac) represents the position of f(h) projected in the frequency characteristics. Repeating the same operation for other f(n) and zeta corresponding to the same f(h), yields the curve of f(h) in the frequency characteristics. Calculations for other f(h)'s provide a group of curves. Frequency characteristics of pulmonary artery catheters were measured and overwritten thereupon, resulting in f(h)'s to be from 1.2 to 3.2 Hz. These results were in agreement with that calculated by the conventional method.     

Relationship between aortic-to-radial arterial pressure gradient after cardiopulmonary bypass and changes in arterial elasticity

BACKGROUND: An aortic-to-radial arterial pressure gradient may develop during and after cardiopulmonary bypass (CPB). The mechanisms of this pressure gradient remain controversial. To clarify the cause of the pressure gradient after CPB, the authors investigated the relationship between the pressure gradient and changes in the pulse wave velocity (PWV) before and after CPB. METHODS: The pressure gradient from the aorta to the radial artery and a change in PWV were measured with a wire (0.37 mm in diameter) tipped with a miniature pressure transducer in 12 patients undergoing cardiac surgery. The pressure distributions and waveforms were measured and recorded with electrocardiograph. The PWV was calculated by measuring the propagation time between the R wave of the electrocardiograph and the rising point of the arterial pressure waveform at 10-cm intervals. RESULTS: After CPB, 7 of 12 patients demonstrated a marked pressure gradient. In these patients, the pressure distribution showed a gradual decrease toward the periphery without a precipitous step-down in pressure at any one specific anatomic location. The PWV decreased as the intraarterial pressure decreased from the aorta to the radial artery, and the relative arterial elasticity decreased linearly toward the periphery. CONCLUSIONS: The results showed that the decrease in PWV implies a decrease in arterial elasticity, and the decrease in the arterial elasticity correlated with the decrease in intraarterial pressure. These findings demonstrated that a radial artery pressure lower than the aortic pressure after CPB may be due to the decrease in arterial elasticity.     

Simultaneous determination of carisoprodol and acetaminophen in an attempted suicide by liquid chromatography-mass spectrometry with positive electrospray ionization

An adult female ingested a considerable quantity of carisoprodol/acetaminophen tablets, which are not commercially available in Japan, in an attempt to commit suicide. Generally, because of lack of the appreciable ultraviolet absorbance or fluorescence, carisoprodol and its major metabolite meprobamate are determined by gas chromatography or gas chromatography-mass spectrometry. Complicated derivatization is, however, necessary to that methodology. Thus, we investigated the derivatization-free, highly sensitive, and simultaneous determination of carisoprodol, meprobamate, and acetaminophen by means of liquid chromatography-mass spectrometry (LC-MS) with positive electrospray ionization. A semi-micro ODS column was used. Ammonium acetate solution (10mM) and acetonitrile were used as mobile phase at a flow rate of 150 microL/min using gradient elution. MS parameters were as follows: capillary voltage, 3.5 kV; cone voltage, +30 V; extractor voltage, 5 kV; and ion source temperature, 100 degrees C. Urine samples pretreated by Oasis HLB cartridge, or plasma samples deproteinized by adding ice-cold acetonitrile were analyzed by LC-MS. The limits of quantitation for each compound were as follows: 0.50 ng/mL for carisoprodol; 10 ng/mL for acetaminophen; and 1.0 ng/mL for meprobamate. In the present case, carisoprodol and acetaminophen were the only drugs detected. Meprobamate was also found as the metabolite of carisoprodol in both urine and plasma. The plasma levels of carisoprodol, acetaminophen, and meprobamate on arrival were 29.5, 245, and 46.7 microg/mL, respectively. These levels were extremely high compared with therapeutic plasma concentrations. Despite the high plasma concentrations of these drugs, which correspond to fatal levels, the patient survived.     

Anesthesia-related mortality and morbidity over a 5-year period in 2,363,038 patients in Japan

BACKGROUND: Statistical data of mortality and morbidity related to anesthesia have not been reported in Japan since World War II. The need to comprehensively examine the events of cardiac arrest as well as mortality prompted the first national study in Japan. METHODS: Confidential questionnaires were sent to all Japan Society of Anesthesiologists Certified Training Hospitals every year from 1994 through 1998. Collected data were analyzed for incidence of cardiac arrest and other critical events during anesthesia and surgery, and their outcomes within 7 postoperative days. The principal causes of the critical incidents were also analyzed. RESULTS: With an average response rate of 39.9%, a total of 2,363,038 cases were documented over 5 years. The average incidence per year of cardiac arrest during surgery due to all etiologies and that totally attributable to anesthesia was 7.12 [95%CI: 6.30,7.94] and 1.00 [0.88, 1.12]) per 10,000 cases, respectively. The average mortality per year in the operating room or within 7 postoperative days due to all etiologies and that totally attributable to anesthesia was 7.18 [6.22, 8.13] and 0.21 [0.15, 0.27] per 10,000 cases, respectively. The two principal causes of cardiac arrest during anesthesia and surgery due to all etiologies were massive hemorrhage (31.9%) and surgery (30.2%), and those totally attributable to anesthesia were drug overdose or selection error (15.3%) and serious arrhythmia (13.9%). Preventable human errors caused 53.2% of cardiac arrest and 22.2% of deaths in the operating room totally attributable to anesthesia. CONCLUSIONS: The rates in Japan of cardiac arrest and death during anesthesia and surgery due to all etiologies as well as those totally attributable to anesthesia are comparable to those of other developed countries.     

Blind endobronchial insertion of a movable bronchial blocker attached to an endotracheal tube, Univent tube

The endotracheal tube with a movable bronchial blocker, Univent tube, used to effect one-lung ventilation is easy to use in endotracheal intubation. However, problems are often encountered when inserting the blocker into the bronchus. We herein describe a method which enables the easy blind insertion of the blocker into the left or right bronchus. The techniques of inserting the blocker into the left main stem bronchus will be described. With the patient in a supine position, the head of the patient is moved to the left. The operator then places his right hand fingers near the cricoid and presses to displace the larynx of the patient toward the right. While performing this procedure, the operator advances the blocker using the left hand. Finally, using a bronchoscope, the placing of the blocker is to be ascertained in an appropriate position inside the left bronchus. When strong resistance is left, the blocker should be retracted, the force of laryngeal displacement is altered and, then, the blocker is inserted again in a resistance-free manner. We have so far experienced no complications such as severe tracheobronchial hemorrhage, tracheobronchial perforation of laryngeal dislocation. We herein describe a useful and simple method for inserting the bronchial blocker of the Univent tube into the bronchus.     

Regulation of the Fanconi anemia pathway by monoubiquitination

Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome characterized by multiple congenital anomalies, bone marrow failure, and cellular sensitivity to mitomycin C (MMC). To date, six FA genes have been cloned, and the encoded proteins function in a novel pathway. The FA pathway is required for the normal cellular response to DNA damage. Following DNA damage, the pathway is activated, leading to monoubiquitination of the FA protein, FANCD2, and its targeting to subnuclear foci. Disruption of the FA pathway results in the absence of FANCD2 nuclear foci, leading to the cellular and clinical abnormalities of FA. Here, we review the recent studies describing the regulated monoubiquitination of the FANCD2 protein and discuss the interaction of the FA pathway with other DNA damage response pathways.     

Development of a novel transdermal patch of alendronate,a nitrogen‐containing bisphosphonate,for the treatment of osteoporosis

Bisphosphonates are widely used for the treatment and prevention of bone diseases, including Paget disease, hypercalcemia of malignancy, and postmenopausal osteoporosis. In this study, we developed a novel transdermal patch of alendronate, a nitrogen‐containing bisphosphonate, for the treatment of bone diseases. The maximum permeation fluxes of alendronate through rat and human skin after application of this patch were 1.9 and 0.3 µg/cm² per hour, respectively. The bioavailability (BA) of alendronate in rats was approximately 8.3% after the application of alendronate patch and approximately 1.7% after oral administration. These results indicated that the transdermal permeation of alendronate using this patch system was sufficient for the treatment of bone diseases. The plasma calcium level was effectively reduced after application of the alendronate patch in 1α‐hydroxyvitamin D₃–induced hypercalcemia model rats. The alendronate patch also effectively suppressed the decrease in bone mass in model rats with osteoporosis. Modest alendronate‐induced erythema of rat skin was observed after application of the alendronate patch. Incorporation of butylhydroxytoluene in the alendronate patch almost completely suppressed this alendronate‐induced skin damage while maintaining the transdermal permeation and pharmacologic effects of alendronate. These findings indicate that our novel transdermal delivery system for alendronate is a promising approach to improve compliance and quality of life of patients in the treatment of bone diseases. © 2010 American Society for Bone and Mineral Research.