A practical tool to assess the incidence of nosocomial infection in Japanese intensive care units: the Japanese Nosocomial Infection Surveillance System.

SUMMARY: Infection control professionals have the means to calculate infection rates in their hospitals but not to assess them. They require a practical tool that enables them to compare observed infection rates with external standards. Based on the data obtained from the intensive care unit (ICU) component of the Japanese Nosocomial Infection Surveillance (JANIS) system, a spreadsheet was developed to calculate a standardized infection ratio (SIR) as a risk-adjusted indicator. Out of the factors associated with the development of nosocomial infections in a multi-variate analysis, the following three factors were selected for stratification: APACHE II score (0-10, 11-20, 21+), operation (yes, no) and ventilator use (user, non-user). Infection rates in 2001 were determined (per 1000 patient-days), stratified by the three factors, as a benchmark. The spreadsheet was designed to calculate SIRs on the basis of the Japanese benchmark infection rates using Microsoft Excel software. The user of the spreadsheet should input the number of observed nosocomial infections and patient-days by APACHE II score, operation and ventilator use. When applied to eight Japanese ICUs, the spreadsheet revealed relative differences and temporal changes in the incidence of nosocomial infections within these ICUs.

Low-dose intramuscular polymyxin B improves survival of septic rats.

UNLABELLED: Polymyxin B (PLB) is a cationic antibiotic that also stoichiometrically neutralizes the lipid A moiety of endotoxin. We examined effects of a small dose of PLB on the mortality of rats with cecal ligation and puncture, on LPS-stimulated nitric oxide (NO) production, and on tumor necrosis factor alpha (TNF alpha) production by isolated rat Kupffer cells. MATERIALS AND METHODS: In vivo studies: Cecal ligation and puncture (CLP) was performed under anesthesia in 28 rats. One hour after CLP, either 600 U/kg of PLB or saline was administered intramuscularly every 6 h (PLB group: n = 12; control group: n = 16). Plasma endotoxin was measured at 3 and 24 h after the CLP by the Endospecy test. This was compared with survival. IN VITRO STUDIES: Kupffer cells were isolated from the normal rat liver. The cells were incubated with LPS or LPS + PLB. After 24 h, NO and TNF alpha content were measured using the Griess and ELISA methods, respectively. RESULTS: Low dose PLB significantly decreased the endotoxin levels at both 3 and 24 h (5.5 +/- 2.1 pg/mL vs. 32.8 +/- 3.6 at 3 h; 26.1 +/- 6.1 vs. 49.1 +/- 5.6 at 24 h (p < .05) after CLP. PLB significantly improved survival of CLP rats (68.8% in the control group vs. 100% in the PLB treated group on 3 days after CLP, p < .001). PLB also attenuated NO and TNF alpha production from the Kupffer cells. CONCLUSION: Intramuscular PLB administered in low doses may improve the mortality of sepsis.

Determination of the optimal pressure support level evaluated by measuring transdiaphragmatic pressure.

The purpose of this study was to determine the optimum pressure support (PS) in six patients with respiratory failure. Esophageal pressure (Pe), gastric pressure (Pg), airway pressure, and transdiaphragmatic pressure (Pdi), obtained by subtracting Pe from Pg, were measured using a newly developed multiluminal nasogastric catheter. For each patient, different PS levels were selected every 20 minutes, and measurements were made at each PS level. We defined the optimum PS level as the level that showed the minimum Pe value. Respiratory rate (RR) decreased and tidal volume (VT) increased with an increase in PS level. RR and VT at the optimum PS were 19.7 +/- 5.5 breaths per minute and 11.7 +/- 4.5 ml/kg, respectively. Pdi decreased linearly with increasing PS level in all patients. Mean Pdi at the optimum Ps was 4.2 +/- 1.2 cm H2O. Based on the relationship between Pdi and PS level, we constructed an equation to estimate the optimum PS level as follows: Optimum PS level = [( Pdi during T-piece mode] - 4)/0.8. We conclude that Pdi measurement is helpful for titrating the required PS level.

Jet flow-regulated expiratory resistance to maintain constant CPAP during the entire respiratory phase.

We have developed a new continuous positive airway pressure (CPAP) device that consists of a microcomputer, a pressure transducer, and a pair of electronic interface valves. One of these valves creates the inspiratory demand flow, and the other creates the opposing jet flow by acting as an expiratory valve to maintain a constant CPAP. By controlling the two electronic interface valves, the airway pressure can be kept constant during the entire respiratory cycle. We compared our device with CPAP systems supplied with commercially available ventilators: the Puritan-Bennett 7200a, the Bear 5, the Servo 900C, and the CV 2000. A two-chambered spring loaded model lung was used to simulate inspiration and a piston pump model lung to simulate active exhalation. We compared both the inspiratory triggering work (WWIt) and expiratory flow-resistive work (WE) of each ventilator while in CPAP mode by calculating the corresponding areas of the pressure-volume loops using electrical integration. The WWIt of our apparatus and demand-flow ventilators was much smaller than that of the CV 2000. In our device, WE was also much smaller than those of the others. These results indicate that our device can be used for CPAP without causing airway pressure fluctuation, and therefore, without imposing an extra workload on the patient.

Comparison of inspiratory work of breathing in T-piece breathing, PSV, and pleural pressure support ventilation (PPSV).

We have compared the inspiratory work of breathing during T-piece breathing, pressure support ventilation (PSV), and pleural pressure support ventilation (PPSV) by using a lung model with variable compliance and resistance, under simulated spontaneous breathing. Our lung model consists of two spring-loaded bellows, representing the lung and diaphragm, placed in an airtight container. Inspiration begins with the withdrawal of air from the diaphragm bellows by a time-cycled jet-flow-creating Venturi mechanism. Expiration occurs by opening the diaphragm bellows to the atmosphere. Work of breathing (WOB) is calculated by plotting the pressure-volume curve, with pressure corresponding to intrabox pressure and volume corresponding to the tidal volume; PPSV is a new mode of mechanical ventilatory support accomplished by setting the ventilator (Servo 900C) into the PSV mode with a level of 0 cm H2O, using the pleural pressure as the input and target signal. The PPSV maximally reduces WOB under any circumstances. The PSV sufficiently reduced WOB only in the normal lung and the lung with low compliance; however, a pressure supporting time is diminished in the lung with low compliance. The serious limitations of PSV remain in its application to the lung with high resistance. It is concluded that PPSV is closer to the actual patient's signal and has a potential advantage in reducing WOB in the lung with low compliance or high resistance (or both). The lung with flow limitation is still a challenging issue for mechanical ventilatory assistance.

Estimation of triggering work of breathing. The dependence on lung mechanics and bias flow during pressure support ventilation.

Work of breathing necessary to trigger a ventilator (WOBtr) was calculated during pressure support ventilation (PSV), and the effect of bias flow on WOBtr was evaluated. A spring-loaded bellows type lung model with two bellows placed in series was used to simulate spontaneous breathing. A Venturi mechanism of jet flow generated subatmospheric pressure inside the diaphragm bellows simulated inspiratory effort. The lung compliance (CL) was set at 0.3 L/cm H2O or 0.05 L/cm H2O. The airway resistance (Raw) was set at 5, 20, or 50 cm H2O/L/s. Pressure support levels were increased from 0 to 45 cm H2O. Sensitivity was set at 2 cm H2O. No bias flow was used at first. The WOBtr was calculated using a pressure-volume (P-V) loop derived from the diaphragm bellows movement during the triggering period. We determined WOBtr and its dependence on the various pressure support (PS) levels, CL and Raw. To evaluate the effects of bias flow on WOBtr and triggering delay, a ventilator was put in the PSV mode, with various bias flow rates (from 0 to 20 L/min) at a sensitivity of 2 cm H2O. We found that when no bias flow was used, WOBtr increased with an increase in both Raw and end-expiratory lung bellows pressure which was considered as auto-PEEP. With bias flow, both triggering delay and WOBtr increased. An increase in bias flow at a given PS level resulted in both decreased pressure support time and tidal volume (VT). It is concluded that the bias flow system is not desirable for use during PSV.

Measurement of functional residual capacity during high-frequency oscillatory ventilation (HFOV) by argon washout method without interruption of HFOV.

A modified indicator gas washout method was developed to measure functional residual capacity (FRC) during high-frequency oscillatory ventilation (HFOV) without interruption of HFOV. A hot-wire flowmeter and medical gas analyzer measured the flow rate and argon concentration, respectively, at the expiratory end of the respiratory circuit. Upstream of the hot-wire flowmeter, two heat-and-moisture exchangers for resistance and a rubber balloon for capacitance were placed to convert the oscillating expiratory flow to an almost continuous flow. This made it possible to measure FRC during HFOV without interrupting HFOV. To measure the volume of the entire respiratory circuit, a 10 percent argon in 90 percent oxygen gas mixture was initially used as a bias flow, and after equilibration, the test gas was switched to 100 percent oxygen. By electrical integration of the product of the expiratory flow rate and argon concentration, the total amount of argon equilibrated in the entire respiratory circuit was calculated. The volume of the circuit was calculated by dividing the total amount of argon by the initial argon concentration. Functional residual capacity plus the volume of the respiratory circuit was similarly calculated and the difference was estimated as FRC. The accuracy and reproducibility of our method were evaluated by using a one-compartment lung model. There was a high correlation between the volume setting of the model lung and the estimated FRC. This method can be used to estimate FRC in a one-compartment lung model during HFOV, and it is potentially useful in clinical situations.

Efficacy of oral treatment with BV-araU against cutaneous infection with herpes simplex type 1 in shaved mice.

The effect of oral BV-araU was tested in cutaneous model infections of shaved Balb/c mice with herpes simplex virus type 1 (HSV-1). Progression of cutaneous symptoms associated with cutaneous infection with HSV-1 F strain was inhibited by BV-araU at doses of 20 and 50 mg/kg twice daily, beginning one day post-infection, resulting in significant increase in the survival rate. Onset of disease was suppressed in most animals receiving 100 mg of BV-araU per kg. BV-araU (20 mg/kg or more) also significantly increased the survival rate of mice infected with HSV-1 WT-51 strain. The efficacy of BV-araU was not affected by gender or age (6-9 weeks) of the mice. BV-araU was effective even when the treatment was started 2.5 days post-infection. The efficacy of BV-araU against F strain infection was comparable to that of acyclovir, but acyclovir showed therapeutic effects at lower doses compared with BV-araU against WT-51 strain infection. Against infection of cyclophosphamide-treated immunosuppressed mice with HSV-1 KOS(S) strain, BV-araU decreased the morbidity rate and severity of symptoms at doses of 200 and 100 mg/kg, respectively, and all mice given 50 mg of BV-araU or more per kg survived, suggesting oral efficacy can be achieved against HSV-1 infections in immunosuppressed individuals.

Gravity-dependent atelectasis. Radiologic, physiologic and pathologic correlation in rabbits on high-frequency oscillation ventilation.

The authors identify the radiologic features of progressive atelectasis induced under conditions of reduced lung volume. Control (n = 5) and experimental (n = 7) animals were placed on high-frequency oscillation (HFO) ventilation (mean airway pressure: 3 cm H2O) for 6 hours. In the experimental animals, lung volume was artificially reduced by pneumoperitoneum during HFO ventilation. Computed tomography scans and chest radiographs were obtained every hour, and arterial blood gases analyzed. No changes were detected in the control animals. In the experimental animals, in which hypoxemia developed, homogeneous opacity in the dependent lung was found on CT images, and chest radiographs showed a diffuse homogenous shadow with loss of lung volume. Study of pathologic sections from the lung showed that the roentgenographic findings represented atelectasis. The lung was divided into three zones, from dependent to nondependent regions: severe atelectasis, mild atelectasis, and normal lung. Hyperinflations eliminated atelectasis seen on the CT images and alleviated hypoxemia; however an undesirable effect that causes barotrauma also was observed.

Effects of different triggering systems and external PEEP on trigger capability of the ventilator.

OBJECTIVE: The triggering capability of both the pressure and flow triggering systems of the Servo 300 ventilator (Siemens-Elema, Sweden) was compared at various levels of positive end-expiratory pressure (PEEP), airway resistance (R(aw)), inspiratory effort and air leak, using a mechanical lung model. DESIGN: The ventilator was connected to a two bellows-in-series-type lung model with various mechanical properties. Lung compliance and chest wall compliance were 0.03 and 0.121/cmH2O, respectively. R(aw) was 5, 20 and 50 cmH2O/l/s. Respiratory rate was 15 breaths/min. To compare the triggering capability of both systems, the sensitivity of pressure and flow triggered pressure support ventilation (PSV) was adjusted to be equal by observing the triggering time at 0 cmH2O PEEP and 16 cmH2O of pressure support (PS) with no air leak. No auto-PEEP was developed. In the measurement of trigger delay, the PS level ranged from 16 to 22 cmH2O to attain a set tidal volume (V(T)) of 470 ml at a R(aw) of 5, 20 and 50 cmH2O/l/s. The PEEP level was then changed from 0, 5 and 10 cmH2O at a PS level of 17 cmH2O and R(aw) of 5 and 20 cmH2O/l/s, and the trigger delay was determined. The effect of various levels of air leak and inspiratory effort on triggering capability was also evaluated. Inspiratory effort during triggering delay was estimated by measurements of pressure differentials of airway pressure (Paw) and driving pressure in the diaphragm bellows (Pdriv) in both systems. MEASUREMENTS AND RESULTS: There were no significant differences in trigger delay between the two triggering systems at the various PEEP and R(aw) levels. At the matched sensitivity level, air leak decreased trigger delay in both systems, and additional PEEP caused auto-cycling. A low inspiratory drive increased trigger delay in the pressure sensing system, while trigger delay was not affected in the flow sensing system. The Paw and Pdriv differentials were lower in flow triggering than in pressure triggering. CONCLUSIONS: With respect to triggering delay, the triggering capabilities of the pressure and flow sensing systems were comparable with and without PEEP and/or high airway resistance at the same sensitivity level, unless low inspiratory drive and air leak were present. In terms of pressure differentials, the flow triggering system may require less inspiratory effort to trigger the ventilator than that of the pressure triggering system with a comparable triggering time. However, this difference may be extremely small.

Application of HPLC measurement of plasma concentration of gabexate mesilate.

The plasma concentration of gabexate mesilate (ethyl-p-(6-guanidinohexanoyloxy) benzoate) methanesulfonate (GM), FOY, was measured on a high performance liquid chromatography. GM concentrations ranging from 1 to 50 micrograms/ml of whole blood were able to be determined with this method. The half-life of GM in plasma was 55 seconds and the minimum concentration of GM which affected the activated coagulation time of whole blood (ACT) was 10 micrograms/ml. This method is sensitive and accurate to provide us with the pharmacodynamic basis for the determination of the effective plasma concentration of GM with respect to its anticoagulant activity.

Inhibitory effect of Apernyl on production of bradykininlike substance in pulp.

In the Formalin-induced pulpitis of rats and the electrically stimulated pulps of dogs, a bradykininlike substance developed by the pulps and released into a saline pool on the exposed pulps disappeared after a local application of Apernyl solution. This suggests that the possible pain-reducing or anti-in-flammatory effect of Apernyl is a result of its inhibiting bradykinin production.

Elevation of N1-acetylspermidine and putrescine in hepatic tissues of patients with fulminant hepatitis and liver cirrhosis.

Hepatic polyamines were assayed in 15 patients with liver diseases, 5 with fulminant hepatitis (FH); 3 with exacerbated liver cirrhosis (ELC); and 7 with liver cirrhosis (LC). Hepatic putrescine and N1-acetylspermidine as percentages of total polyamines, were elevated and spermine was decreased in all 15 patients. The increase in hepatic N1-acetylspermidine levels appeared to be greater in patients with FH and ELC than in those with LC. These results suggest that the production of N1-acetylspermidine in human liver is closely associated with the induction of spermidine/spermine N1-acetyltransferase activity in liver diseases.

Urinary excretion of cyclic nucleotides and principal electrolytes in healthy humans of different ages.

Urinary excretion of cyclic AMP, cyclic GMP, inorganic phosphorus, calcium, sodium, potassium and creatinine was measured in 138 healthy male and 104 healthy female humans from 2 to 68 years old. The range of cyclic nucleotide excretion was as follows: cyclic AMP (mumol/day), 1.01-10.89; cyclic GMP (mumol/day), 0.13-2.00; cyclic AMP (mumol/g creatinine), 1.52-8.93; cyclic GMP (mumol/g creatinine), 0.11-1.87. The 242 volunteers were grouped into seven classes according to age: A, 2-9 years old; B, 10-19; C, 20-29; D, 30-39; E, 40-49; F, 50-59 and G, 60-68. Average excretion (mumol/day) of cyclic AMP in class A (2.62 +/- 0.29 for males and 2.30 +/- 0.18 for females) was significantly smaller than that in other classes (4.59 +/- 0.12 for males and 3.90 +/- 0.13 for females) (p less than 0.01). Such a significant difference was not observed in cyclic GMP excretion. In terms of mumol/g creatinine, however, average excretion of both cyclic AMP and cyclic GMP in class A was greater than that in other classes. The amounts of urinary cyclic AMP and cyclic GMP (mumol/day) were correlated with age in the subjects from 2 to 16 years. A reverse correlation between the amounts of both nucleotides (mumol/g creatinine) and age was found in the young subjects. No correlation between the excretion of either urinary cyclic nucleotide and age was found in adults. A significantly positive correlation between cyclic AMP (mumol/day) and inorganic phosphorus (g/day) was found (r = 0.50 for males and 0.56 for females) (p less than 0.01). This correlation suggests that urinary cyclic AMP might reflect the activity of parathyroid hormone in normal humans. There was no significant correlation between cyclic GMP and electrolytes tested. The above results are considered to provide basic data for clinical evaluation of relevant disorders.

A comparison of the effects of paraquat and diquat on lung compliance, lung volumes and single breath diffusing capacity in the rat.

Paraquat intoxication in its initial stage is characterized histologically in the lungs by atelectasis, hyaline membrane formation, alveolar edema and vascular hemorrhage often into the interstitium or air spaces. Information on the functional modification of paraquat-damaged lungs has been lacking. We evaluated lung volumes, single breath diffusing capacity of the lungs for carbon monoxide (DLCO) and static lung compliance (Cst(L)) in rats treated with paraquat or diquat. Measurements were made 12, 24, 48, and 72 h after treatment. Paraquat by intratracheal (i.t.) instillation 0.5 mg/kg or by intraperitoneal injection (i.p.) 27 mg/kg significantly decreased (P less than 0.01) the body weight, total lung capacity (TLC), functional residual capacity (FRC), vital capacity (VC), residual volume (RV), DLCO, apparent alveolar volume (VA) and Cst(L). At a lower dose level (13.5 mg/kg), the effects of paraquat peaked at about 24 h following treatment, causing a significantly decreased (P less than 0.01) VC and TLC. Diquat i.t. or i.p. had little effect on the lungs. However, diquat i.p. decreased body weight (P less than 0.01) and caused a slight increase (P less than 0.05) in VC. The data obtained are consistent with the known pathological changes seen in paraquat-damaged lungs in that, by both routes, paraquat caused severe lung damage associated with decreased elasticity of the lungs and thorax, destruction of gas exchanging alveolar surfaces, and edema. These changes were detected reliably by lung function measurements.

Autonomous control of expression of genes for insulin-like growth factors during the proliferation and differentiation of C2C12 mouse myoblasts in serum-free culture.

The proliferation and differentiation of skeletal muscle cells in culture are usually controlled by serum components, and the differentiation can be induced by a reduction in the serum concentration. Insulin-like growth factors (IGFs) play a critical role in stimulating myoblast differentiation, and the expression of their genes is controlled by serum factors. We have found that C2C12 myoblasts are capable of proliferation and differentiation even in serum-free medium that does not contain peptide mitogens. During these processes in serum-free medium, the accumulation of mRNAs for IGFs in the cells was observed; and their levels increased with concomitant increases in creatine kinase activity and myotube formation and a decrease in DNA synthesis. Thus, the present results suggest that proliferation and differentiation of C2C12 cells are autonomously controlled and that the increase in the expression of the IGFs may be independent of exogenous components.

Stereospecific effects of d- and l-pentazocine on contractions of the mouse vas deferens.

The effects of the d- and l-isomers of pentazocine were compared to that of racemic pentazocine on contractions of the mouse isolated vas deferens. L-pentazocine inhibited electrically evoked contractions of the mouse vas deferens (MVD) in a dose-dependent manner (ID50 0.37 +/- 0.04 microM). In contrast, d-pentazocine augmented field stimulated contractions dose-dependently; per cent increases in contractions at 10 and 30 microM were 57.8 +/- 18.0 and 98.0 +/- 15.1%, respectively. Racemic pentazocine produced an intermediate effect between the two isomers. The effect of 1-pentazocine was antagonized by naloxone, whereas that of d-pentazocine was not. L-pentazocine did not effect the response of the MVD to exogenous norepinephrine at any concentration tested, while d-pentazocine depressed the response of the MVD to exogenous norepinephrine at one dose (0.3 microM). These findings demonstrate that d- and l-pentazocine produce opposite effects on the MVD. The effects of l-pentazocine are opioid mediated, while those of d-pentazocine are not. In the racemic mixture the opposing effects of the two isomers modulate each other, resulting in a diminished effect.

Acute fatty liver of pregnancy showing microbial infection in the liver.

A 24-year-old, nulliparous woman in her 30th week of pregnancy was admitted due to threatened premature delivery. Ritodrin chloride relieved the premature contraction of the uterus but jaundice and drowsiness appeared 7 weeks later. Laboratory data revealed disseminated intravascular coagulation (DIC) with intrahepatic cholestasis, and ultrasound examination showed fatty liver. The patient was diagnosed with acute fatty liver of pregnancy (AFLP). Emergency delivery by Caesarean section was performed at 37 weeks of pregnancy and the liver function and DIC improved immediately. Liver biopsy 13 days after delivery showed nuclear swelling and cytoplasmic ballooning with mild fatty deposition. These findings were relatively compatible with acute AFLP. Higher magnification and electron microscopy revealed intracytoplasmic bacteria and fungus in the residual stage. The bacterial infection could be considered related to AFLP.

Evaluation of a new reflectance pulse oximeter for clinical applications.

The design of a noninvasive reflectance pulse oximeter that uses the same principle of transmittance pulse oximeter and analyses the oxygen saturation of arterial blood was described. Four sets of red and infra-red LEDs were used as light sources. The respective reflectance photoelectric outputs were used to make an internal calibration curve of the instrument relative to the arterial oxygen saturation values measured with a Co-Oximeter (OSM-3) in five healthy nonsmoking subjects during steady-state hypoxaemia. The accuracy of the present instrument was studied in six patients with respiratory failure. From 22 samples, a good correlation coefficient (0.98) with a standard deviation of 1.42 was obtained in the range between 73 and 100 per cent between the arterial oxygen saturation measured with the present instrument and that with the Co-Oximeter. The result strongly suggests the usefulness of this oximeter in monitoring patients with hypoxaemia.

Histological change after interferon therapy in chronic hepatitis C in view of iron deposition in the liver.

We examined the efficacy of interferon (IFN) therapy for chronic hepatitis C (CHC) in view of the change of liver histology and iron staining before and after IFN therapy. Enrolled in this study were 109 patients with CHC who completed IFN treatment and were followed for at least 1 yr after the end of IFN therapy. Serum iron, unsaturated-iron-binding capacity (UIBC), and total-iron-binding capacity (TIBC) were assessed before IFN therapy. Knodell's histological activity index (HAI) score and iron staining were examined in 55 patients in whom liver biopsy was performed at two points: before and. 1 yr after IFN therapy. Serum iron levels before IFN therapy did not correlate with the response to IFN. The HAI score significantly decreased after IFN therapy in complete responders (p < 0.01) and biochemical responders (p < 0.01). Three factors in the HAI, periportal necrosis, intralobular necrosis, and portal inflammation, but not fibrosis, were significantly decreased in complete responders (p < 0.01) and biochemical responders (p < 0.01). Of 55 patients, 23 (41.8%) were positive for iron staining before IFN therapy and 14 of 55 (25.5%) after IFN therapy. The positive rate for iron staining tended to decrease after IFN therapy, not correlating to the response to IFN, but the change was not statistically significant. In conclusion, the histological improvement by IFN therapy was mostly seen in necroinflammatory changes but not in fibrosis at least 1 yr after IFN, and iron staining tended to decrease after IFN therapy.