Thromboelastometry-guided intraoperative haemostatic management reduces bleeding and red cell transfusion after paediatric cardiac surgery.

BACKGROUND: Thromboelastometric evaluation of coagulation might be useful for prediction and management of bleeding after paediatric cardiac surgery. We tested the hypothesis that the use of a thromboelastometry-guided algorithm for blood product management reduces blood loss and transfusion requirements. METHODS: We studied 78 patients undergoing paediatric cardiac surgery with cardiopulmonary bypass (CPB) for the initial 12 h after operation. Stepwise multiple linear regression was used to develop an algorithm to guide blood product transfusions. Thereafter, we randomly assigned 100 patients to conventional or algorithm-guided blood product management, and assessed bleeding and red cell transfusion requirements. RESULTS: CPB time, post-bypass rotational thromboelastometry (ROTEM(®)) EXTEM amplitude at 10 min (A10), and FIBTEM-A10 were independently associated with chest tube drainage volume during the initial 12 h after operation. Discriminative analysis determined cut-off values of 30 mm for EXTEM-A10 and 5 mm for FIBTEM-A10, and estimated optimal intraoperative fresh-frozen plasma and platelet concentrate transfusion volumes. Thromboelastometry-guided post-bypass blood product management significantly reduced postoperative bleeding (9 vs 16 ml kg(-1), P<0.001) and packed red cell transfusion requirement (11 vs 23 ml kg(-1), P=0.005) at 12 h after surgery, and duration of critical care stay (60 vs 71 h, P=0.014). CONCLUSIONS: Rotational thromboelastometry-guided early haemostatic intervention by rapid intraoperative correction of EXTEM-A10 and FIBTEM-A10 reduced blood loss and red cell transfusion requirements after CPB, and reduced critical care duration in paediatric cardiac surgical patients. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000006832 (December 4, 2011).

Higher expression of deoxyuridine triphosphatase (dUTPase) may predict the metastasis potential of colorectal cancer.

AIMS: 5-Fluorouracil (5-FU) is one of the most widely used anticancer drugs; however, the activity of 5-FU is determined by the presence of several enzymes that limit its activation or degradation, and these include dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), thymidine kinase (TK), thymidine phosphorylase (TP) and deoxyuridine triphosphatase (dUTPase). The aim of this study was to compare the expression levels of these enzymes between the primary colorectal cancer of patients with and without distant metastases. Furthermore, there was a comparison of these expression levels between the primary tumour and the corresponding metastasis. METHODS: Of 55 patients with colorectal cancer, 20 had no metastasis and the other 35 had distant metastasis. A strong expression was classified as positive, while weak to moderate or no expression was negative by immunohistochemistry. RESULTS: Of the six 5-FU-related enzymes, the numbers of patients with expression of dUTPase (54% versus 15%; p = 0.005), TK (26% versus 0%; p = 0.019) and DPD (17% versus 45%; p = 0.033) were significantly different in those with primary tumours with metastasis compared with those with non-metastasis, respectively. The altered expression of OPRT (34.3%), TS (40.0%) and dUTPase (42.9%) was significantly greater from primary to metastasis among the 35 patients with metastasis. By contrast, the expression of OPRT, TS and dUTPase was decreased in 6, 5 and 7 patients, respectively, in metastatic sites. CONCLUSIONS: From this comparative study of the six 5-FU-related enzymes in colorectal cancer, the expression of dUTPase was most significantly different between primary tumours and their corresponding metastatic tumour. It is suggested that dUTPase may be a predictive biomarker for the metastatic potential of colorectal cancer.

Increased platelet, leukocyte, and endothelial cell activity are associated with increased coagulability in patients after total knee arthroplasty.

BACKGROUND: Orthopedic surgery, especially total knee and total hip arthroplasty, is considered a risk factor for peri-operative venous thromboembolism. OBJECTIVES: This study evaluates how accelerated inflammatogenic cellular interactions and the subsequent production of tissue factor and CD40 ligand play an important role in the pathogenesis of venous thromboembolism. PATIENTS AND METHODS: Twenty-four patients undergoing total knee arthroplasty were randomly assigned to groups with (Ti; n = 12) and without (Tn; n = 12) pneumatic tourniquet inflation. RESULTS: Numbers of leukocyte-platelet aggregates, especially those comprising monocytes-platelets in central venous blood from the Ti group, were increased during the peri-operative period (P < 0.01), and returned to the baseline level at 24 h after starting surgery. Levels of PAC-1, P-selectin, CD40 ligand, tissue factor, Mac-1 expression on monocytes including monocyte-platelet aggregates, and the number of microparticles including those of endothelial cell origin were noticeably increased in central venous blood from the Ti group (P < 0.01). Whole blood coagulability was also obviously increased in central venous blood from the Ti group (P < 0.01). Furthermore, the concentrations of venous plasma tissue factor antigen, CD40 ligand, platelet factor 4, beta-thromboglobulin, the soluble fibrin monomer complex and prothrombin fragment 1+2 were also increased (P < 0.05). CONCLUSIONS: This study showed that platelet, leukocyte and endothelium activities as well as their interactions are enhanced during the peri-operative period of total knee arthroplasty, particularly in venous blood from the lower half of the body, which consequently augments blood coagulability. Further, tourniquet inflation during surgery exaggerates these responses.

Predictors of atrial fibrillation after off-pump coronary artery bypass graft surgery.

BACKGROUND: Postoperative atrial fibrillation (AF) is one of the most common complications after cardiothoracic surgery and is associated with an increased risk of stroke, and longer hospital stay. The pathophysiology of postoperative AF is uncertain, and its prevention remains unsatisfactory. Many previous studies have examined the predictors of AF after on-pump coronary artery bypass graft surgery (CABG), but there are few reports after off-pump CABG. METHODS: The aim of the present prospective observational study, in which 296 consecutive patients were enrolled, was to elucidate the predictors of AF after off-pump CABG. The association of perioperative factors with AF was investigated using univariate analysis. Significant variables were included into a stepwise logistic regression model to ascertain their independent influence on the occurrence of AF. RESULTS: The incidence of AF was 32%. AF prolonged the time until patients were fit for discharge by 3 days (P<0.01). Stepwise multivariate analysis identified increasing age [odds ratio (OR) 1.44 per 10-yr increase; 95% confidence interval (CI) 1.06-1.95], intraoperative average core temperature (OR 1.64; 95% CI 1.05-2.56), the average cardiac index in the intensive care unit (OR 0.37; 95% CI 0.19-0.71), and intraoperative fluid balance (OR 0.96 per 100-ml increase; 95% CI 0.93-0.99) as independent predictors of postoperative AF. CONCLUSION: Our present findings indicate that ageing, the intraoperative fluid balance, and postoperative cardiac index are associated with the onset of AF after off-pump CABG.

Clonidine produces a dose-dependent impairment of baroreflex-mediated thermoregulatory responses to positive end-expiratory pressure in anaesthetized humans.

BACKGROUND: Perioperative hypothermia is common and results from anaesthesia-induced inhibition of thermoregulatory control. Hypothermia is blunted by baroreceptor unloading caused by positive end-expiratory pressure (PEEP), and is mediated by an increase in the vasoconstriction threshold. Premedication with clonidine impairs normal thermoregulatory control. We therefore determined the effect of clonidine on PEEP-induced hypothermia protection. METHODS: Core temperature was evaluated in patients undergoing combined general and epidural anaesthesia for lower abdominal surgery. They were assigned to an end-expiratory pressure of zero (ZEEP) or 10 cm H(2)O PEEP. The PEEP group was divided into three blinded subgroups that received placebo (Cl-0), clonidine 150 microg (Cl-150) and clonidine 300 microg (Cl-300) respectively. Placebo or clonidine was given orally 30 min before surgery. We evaluated core temperature and thermoregulatory vasoconstriction. We also determined plasma epinephrine, norepinephrine, angiotensin II concentrations and plasma renin activity. RESULTS: Core temperature after 180 min of anaesthesia was 35.1 (0.4) degrees C in the ZEEP group. PEEP significantly increased final core temperature to 35.8 (0.5) degrees C (Cl-0 group). Clonidine produced a linear, dose-dependent impairment of PEEP-induced hypothermia protection: final core temperatures were 35.4 (0.3) degrees C in the Cl-150 group and 35.0 (0.6) degrees C in the Cl-300 group. Similarly, clonidine produced a linear and dose-dependent reduction in vasoconstriction threshold: Cl-0, 36.4 (0.3) degrees C; Cl-150, 35.8 (0.3) degrees C; Cl-300, 35.4 (0.6) degrees C. Plasma norepinephrine, angiotensin II concentrations and renin activity were consistent with the thermoregulatory responses. CONCLUSION: Baroreceptor unloading by PEEP normally moderates perioperative hypothermia. However, clonidine premedication produces a linear, dose-dependent reduction in this benefit.

Development of an ankle-foot orthosis with an oil damper.

The purpose of the present study was to develop an ankle-foot orthosis (AFO) that satisfies the requirements for an AFO for patients with hemiplegia as determined in a previous study. An oil damper has been introduced as an assistive device. The oil damper provides a resistive moment to plantar flexion of the ankle joint during initial stance on the paretic side. This function improves the insufficient eccentric contraction of the dorsiflexors. The magnitude of the resistive moment generated by this newly developed AFO can be changed easily to adjust its properties in accordance with the requirements of each patient. The mechanical properties of the AFO were measured, and the results showed that the AFO generated a sufficient resistive moment. Hemiplegic gaits with various types of AFOs were assessed, and it was found that the properties of the AFO affected the movements of the ankle, the knee, and the hip joints. The effects of the resistive moment on the alignment of the shank to the floor during initial stance are also discussed. Based on the results of this study, it is concluded that adjustability will be an essential feature for future AFOs.

Effect of preoperative amino acid infusion on thermoregulatory response during spinal anaesthesia.

BACKGROUND: Intravenous amino acid infusion during general anaesthesia prevents decreases in core temperature resulting from increased energy expenditure and heat accumulation. METHODS: We investigated whether such stimulation also occurs during spinal anaesthesia, which blocks sympathetic nervous activity. We examined the effect of i.v. amino acid infusion on changes in core temperature during spinal anaesthesia. Thirty-five patients were divided into two groups: an i.v. amino acid infusion group (4 kJ kg(-1) h(-1) starting 2 h before surgery); and a saline infusion group. Tympanic membrane core temperature, forearm-fingertip temperature gradient (an index of peripheral vasoconstriction) and mean skin temperature were measured for 90 min after the onset of spinal anaesthesia. RESULTS: Changes in mean arterial pressure and heart rate did not differ significantly between the groups during the study period. Mean final core temperature 90 min after induction of spinal anaesthesia was 35.8 (SEM 0.1) degrees C in the saline group and 36.6 (0.1) degrees C in the amino acid group (P<0.05). The increased level of oxygen consumption in the amino acid group compared with the saline group was preserved even after the onset of spinal anaesthesia. The thermal vasoconstriction threshold, defined as the tympanic membrane temperature that triggered a rapid increase in forearm-fingertip temperature gradient, was increased in the amino acid group [36.8 (0.1) degrees C] compared with the saline group [36.5 (0.1) degrees C] (P<0.05). CONCLUSIONS: Preoperative infusion of amino acids effectively prevents spinal anaesthesia-induced hypothermia by maintaining a higher metabolic rate and increasing the threshold core temperature for thermal vasoconstriction.

[Anesthesia for a patient with alcoholic heart disease and transient complete heart block].

A 70-year-old man who had been drinking a bottle of whisky each day was scheduled for laser resection of a tongue tumor. His electrocardiogram showed sinus bradycardia (heart rate was 35-40 bpm), and transient complete heart block was observed. Echocardiography showed hypertrophic cardiomyopathy. After a temporary transvenous pacemaker had been inserted, anesthesia was induced with thiopental and vecuronium bromide, and maintained with sevoflurane and fentanyl. Heart rate was 45.min-1 before the induction of anesthesia, and after the induction increased to 70-80.min-1. Analysis of heart rate variability suggested that the increase in heart rate was due to augmentation of sympathetic nervous activity after intubation and operation stress. After the operation his bradycardia improved gradually, and after 3 months heart rate settled at about 55.min-1. Cadiomyopathy is known to be one of the complications of alcoholism. It was reported that alcoholic heart disease was improved promptly by abstinence from alcohol. During his long hospitalization, abstinence might have improved his severe bradycardia. Thiopental is useful for induction of anesthesia in a patient with severe bradycardia from alcoholic cadiomyopathy.

[Adrenergic receptor and knockout mouse: 2). Alpha adrenergic receptor knockout mouse].

The sympathetic nervous system regulates cardiovascular function by activating adrenergic receptors which are known to have a critical role in regulating transmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. alpha 2A adrenergic receptor knockout mouse (alpha 2A-KO) showed an increase in sympathetic activity with resting tachycardia, depletion of cardiac tissue norepinephrine concentration. Knockout mouse study reveals that the alpha 2B adrenoceptor (alpha 2B AR) mediates the hypertensive response, and the alpha 2A AR mediates the hypotensive response, induced by alpha 2 agonists. Both the alpha 2A and alpha 2C AR subtypes are required for normal presynaptic control of transmitter release from sympathetic nerves. alpha 2A AR subtype inhibits transmitter release at high stimulation frequencies, whereas the alpha 2C AR subtype modulates neurotransmission at lower levels of nerve activity. Salt-induced hypertension experiment using alpha 2B-KO and alpha 2C-KO revealed that alpha 2B AR subtype is necessary to raise BP in response to dietary salt loading. Lack of adequately functional renal alpha 2B AR is thought to preclude reabsorption of sodium. alpha 1B-KO study revealed that alpha 1B AR is a mediator of the blood pressure response and the aorta contractile response induced by alpha 1 agonists.

Baroreflex modulation of peripheral vasoconstriction during progressive hypothermia in anesthetized humans.

Mild hypothermia is a major concomitant of surgery under general anesthesia. We examined the hypothesis that baroreceptor loading/unloading modifies thermoregulatory peripheral vasoconstriction and, consequently, body core temperature in subjects undergoing lower abdominal surgery with general anesthesia. Thirty-six patients were divided into four groups: control group (C), applied positive end-expiratory pressure (PEEP; 10 cmH(2)O) group (P), applied leg-up position group (L), and a group of leg-up position patients with PEEP starting 90 min after induction of anesthesia (L + P). The esophageal temperature (T(es)) and the forearm-fingertip temperature gradient, as an index of peripheral vasoconstriction, were monitored for 3 h after induction of anesthesia. Mean arterial pressure and pulse pressure did not change during the study in any group. The change in right atrial transmural pressure from the baseline value was 0.3 +/- 0.1 mmHg in C, -3.0 +/- 0.5 mmHg in P, and 2.3 +/- 0.4 mmHg in L (P < 0.01). The change in T(es) at the end of the study was -1.7 +/- 0.1 (35.1 +/- 0.1) degrees C in C, -1.1 +/- 0.1 (35.7 +/- 0.1) degrees C in P, and -2.7 +/- 0.1 (34.1 +/- 0.1) degrees C in L, showing significant differences (P < 0.01). The T(es) threshold for thermal peripheral vasoconstriction was 35.6 +/- 0.1 degrees C in C, 36.2 +/- 0.2 degrees C in P, and 34.8 +/- 0.2 degrees C in L (P < 0.01). Excessive T(es) decrease in the leg-up-position operation was attenuated by applying PEEP (L + P group; P < 0.05). Our data indicate that baroreceptor loading augments and unloading prevents perioperative hypothermia in anesthetized and paralyzed subjects by reducing and increasing the body temperature threshold for peripheral vasoconstriction, respectively.

Bacterial superantigen staphylococcal enterotoxin B induces interstitial pneumonia in SCID mice reconstituted with peripheral blood mononuclear cells from collagen vascular disease patients.

To investigate whether superantigens induce interstitial pneumonia associated with collagen vascular disease (CVD), staphylococcal enterotoxin B (SEB) was intratracheally administered to SCID mice reconstituted with peripheral blood mononuclear cells (PBMCs) from CVD patients that suffered lung complications. Although a slight accumulation of inflammatory cells into the perivascular area was seen in the lungs of SCID mice injected with PBMCs from CVD patients or healthy donors, SEB administration significantly increased the severity of inflammation in the lungs of SCID mice that received CVD patient PBMCs. Furthermore, human leukocytes were detected by immunohistochemistry in the lungs of SCID mice that received SEB after reconstitution with PBMCs from CVD patients but not in other groups of SCID mice. CD45RO(+) memory T cells comprised the majority of infiltrating human leukocytes. These results suggest the possibility that external superantigens may induce the development of interstitial pneumonia in patients that have a genetic background predisposition to autoimmune disease.

Sevoflurane does not inhibit human platelet aggregation induced by thrombin.

BACKGROUND: Sevoflurane reportedly inhibits adenosine diphosphate-induced platelet aggregation by suppressing thromboxane A2 formation. The increase in intracellular calcium concentration that fosters platelet aggregation, however, is also induced by other cell signaling pathways, such as activation of the production of inositol 1,4,5-triphosphate by thrombin. The current study aimed to clarify the net influence of sevoflurane on thrombin-induced platelet aggregation. METHODS: Washed platelets were stimulated by thrombin after incubation with 0.5, 1.0, or 1.5 mM sevoflurane, halothane, or isoflurane. Aggregation curves were measured by an aggregometer. Intracellular calcium concentration was measured fluorometrically using fura-2. Calcium mobilization via plasma membrane calcium channels and the dense tubular system was assessed differentially. Intracellular inositol 1,4,5-triphosphate was measured by radioimmunoassay. RESULTS: Halothane significantly suppressed aggregation ratios at 5 min compared with those in controls (89 +/- 7%) to 71 +/- 10% (1.0 mM) and 60 +/- 11% (1.5 mM) and the increase in intracellular calcium concentration (controls, 821 +/- 95 nM vs. 440 +/- 124 nM [1.0 mM] or 410 +/- 74 nM [1.5 mM]). Halothane also significantly inhibited release of calcium from the dense tubular system (controls, 220 +/- 48 nM vs. 142 +/- 31 nM [1.0 mM]). Neither sevoflurane nor isoflurane produced a net change in aggregation ratios, intracellular calcium concentration, or calcium mobilization. Halothane (1 mM) significantly suppressed inositol 1,4,5-triphosphate concentrations, whereas neither 1 mM isoflurane nor 1 mM sevoflurane had any effect. CONCLUSIONS: Although sevoflurane has been reported to inhibit human platelet aggregation induced by weak agonists such as adenosine diphosphate, it does not inhibit human platelet aggregation induced by strong agonists such as thrombin.

[Adrenergic receptor and knockout mouse: 1) Beta adrenergic receptor knockout mouse].

Functional analysis of beta 1 and beta 2 adrenergic receptor (AR) subtypes has been made possible by establishing knockout mice (KO) with abolished beta 1 and/or beta 2 AR expression. Neither resting heart rate nor resting blood pressure of beta 1 AR KO, beta 2 AR KO, or beta 1/beta 2 KO differed significantly from those of wild-type mice. The chronotropic response to isoproterenol was significantly attenuated in beta 1 AR KO and beta 1/beta 2 KO, whereas there was no detrimental effect on heart rate in beta 2 AR KO. This suggests that chronotropy is mediated by beta 1 AR. In terms of the vasodilatory response to isoproterenol, there appears to be a graded and additive attenuation of the hypotensive response in beta 1 AR KO, beta 2 AR KO, and beta 1/beta 2 KO. Vascular relaxation is thought to be controlled by both beta 1 AR and beta 2 AR. Tachycardia induced by exercise was significantly attenuated in beta 1 AR KO, and beta 1/beta 2 KO. beta 2 AR KO subjected to treadmill exercise showed significant hypertension, increased oxygen consumption, and ability of long distance running.

[A case of rhabdomyolysis after open heart surgery in a child].

Rabdomyolysis usually occurs after trauma and release of myoglobin from the damaged muscle, i.e.; after ishchemic myopathy due to arterial occlusion or malignant hyperthermia. We encountered a pediatric case of rhabdomyolysis after Ross-Konnos' operation in an 8-yr-old girl with aortic regurgitation. After the first weaning from cardiopulmonary bypass (CPB), ventricular fibrillation occurred due to an insufficiency in coronary blood flow and CPB was resumed with rapid cooling of body temperature. The total CPB lasted for 5 hr 43 min. After the second weaning from CPB, myoglobinuria was found. Furthermore, blisters and abrasions appeared on her back and CPK levels were abnormally elevated (maximum 19,132 IU.l-1) without any elevation of body temperature in the postoperative course. Rhabdomyolysis due to intraoperative hypoperfusion was suspected and diuretics were administrated with a large amount of crystalloid to maintain urine output. The patient showed a good clinical course without acute renal failure. The course of this case suggests that rhabdomyolysis is one of rare complications of CPB and an early correct diagnosis of rhabdomyolysis and forced diuresis at an early stage are important to avoid acute renal failure.

[Postoperative hoarseness and sore throat after tracheal intubation: effect of a low intracuff pressure of endotracheal tube and the usefulness of cuff pressure indicator].

Many clinical reports have described postoperative hoarseness and sore throat after general anesthesia. In most cases, these symptoms were attributed to high pressure of the endotracheal tube cuff. The recommended cuff pressure is less than 25 mmHg, as excessive pressure produces ischemia of the tracheal mucosa. However, within the safe pressure range, postoperative hoarseness and sore throat are still often observed. In this study, one hundred and ninety patients of ASA classes I or II were allocated randomly to two groups, low cuff pressure group (< 15 mmHg) or high cuff pressure group (15-25 mmHg), using continuous monitoring with a cuff pressure gauge. We investigated the incidence of postoperative hoarseness and sore throat at 24 hours after intubation and on the seventh postoperative day. The incidence of postoperative hoarseness and sore throat was significantly decreased in the low pressure group at 24 hours after intubation as compared with the high pressure group, but there was no significant difference between the two groups on the seventh postoperative day. These results suggest that keeping the cuff pressure under 15 mmHg can prevent postoperative hoarseness or sore throat at 24 hours after intubation, and that a cuff pressure gauge is thought to be one of the indispensable monitors during anesthesia.

Functional roles of MCP-1 in Propionibacterium acnes-induced, T cell-mediated pulmonary granulomatosis in rabbits.

The immunological manifestation of granuloma formations in humans largely depends on the delayed-type hypersensitivity response. We investigated the involvement of monocyte chemoattractant protein-1 (MCP-1) in a rabbit model of T cell-mediated pulmonary granulomatosis. Intravenous injection of Propionibacterium acnes (P. acnes) into sensitized rabbits induced massive and diffuse pulmonary granulomas. Levels of MCP-1 in sera and bronchoalveolar lavage fluids (BALF) peaked before the granuloma formation reached the peak (on days 1 and 3 after challenge, respectively). Chemotactic activities toward monocytes and T cells in BALF were inhibited by anti-MCP-1 IgG by 80 and 36%, respectively. The phenotypic analysis of the migrating T cells revealed that activated and memory T cells rather than naive cells were preferentially attracted to the BALF. Administration of anti-MCP-1 antiserum inhibited the development of granuloma formation in both size and number, the numbers of infiltrating leukocytes in BALF, the expression of adhesion molecules on peripheral monocytes/T cells, and on macrophages/T cells in BALF, and the production of TNF-alpha in the lung. Anti-MCP-1 resulted in a trend toward decreased level of IL-1beta in the lung. The inhibition of the production of these cytokines appeared to be induced indirectly through the inhibition of the recruitment of macrophages that produce these cytokines. The results suggest important roles of MCP-1 in the development of granuloma formation in this model through the attraction and activation of specific types of cells.

Haematological effects of anaesthetics and anaesthesia.

Halothane is still unique in its ability to inhibit platelet aggregation and to increase bleeding time in vivo at clinical concentrations, although sevoflurane inhibits platelet aggregation induced by weak agonists. Propofol itself, but not its fat emulsion, inhibits platelet aggregation and suppresses calcium mobilization. Extradural anaesthesia has been shown to prevent hypercoagulability during the perioperative period. Aprotinin reduces both blood loss and the incidence of blood transfusion during major orthopaedic and cardiac surgery.

[Severe bronchorrhea accompanying alveolar cell carcinoma: treatment with clarithromycin and inhaled beclomethasone].

We report the efficacy of oral clarithromycin and inhaled beclomethasone against severe bronchorrhea in a patient with alveolar cell carcinoma. A 54-year-old man produced about 500 to 900 ml of clear and egg-white-like sputum each day. Anti-cancer chemotherapy and erythromycin therapy did not reduce the volume of sputum. After administration of clarithromycin and inhaled beclomethasone, sputum volume decreased to about 300 nl each day and the patient's ability to perform daily activities improved. Two months later, clarithromycin was stopped and the patient was treated with inhaled beclomethasone alone. Sputum volume did not increase for 6 months, although the chestroentgenographic findings gradually worsened. Then the sputum volume gradually increased. Five months after the sputum volume began to increase, he was producing about 2 liters of sputum each day and died of respiratory failure. Although the levels of CA 19-9, SLX, and CEA in serum were all within the normal range, the sputum contained high levels of CA 19-9 (1,133,620 U/ml), SLX (3,000 U/ml), and CEA (283 ng/ml). In patients with bronchorrhea, measurement of tumor markers in sputum may be useful for the diagnosis of alveolar cell carcinoma.

In vivo and in vitro studies of the inhibitory effect of propofol on human platelet aggregation.

BACKGROUND: The inhibitory effects of propofol on platelet aggregation are controversial because the fat emulsion used as the solvent for propofol may affect platelet function. The effects of propofol on platelet intracellular calcium ion concentration and on aggregation were investigated. METHODS: Platelet aggregation was measured in 10 patients who received an intravenous infusion of propofol. Intralipos, the propofol solvent, was infused in 10 healthy volunteers and platelet aggregation were measured. The in vitro effects of propofol and Intralipos on platelets were also investigated. The inhibitory effects of various concentrations of propofol were studied. The effects of propofol on the changes in intracellular calcium level using a fluorescent dye, fura-2, were also observed. Template bleeding time was measured to determine the effect of propofol in clinical use. RESULTS: Platelet aggregation was significantly inhibited by infusion of propofol, although bleeding time was not prolonged. Intralipos did not inhibit platelets either in vivo or in vitro. Propofol significantly inhibited platelet aggregation in vitro and at 5.81 +/- 2.73 microg/ml but not at 2.08 +/- 1.14 microg/ml. The increase of intracellular calcium concentration was inhibited both in influx and discharge of calcium. CONCLUSIONS: Propofol inhibited platelet aggregation both in vivo and in vitro. Inhibition of platelet aggregation appeared to be caused by propofol itself and not by the fat emulsion. This inhibitory effect was also supported by the suppressed influx and discharge of calcium. No change in the bleeding time suggests that this inhibitory effect does not impair hemostasis clinically.