Time course of expiratory flow limitation in COPD patients during acute respiratory failure requiring mechanical ventilation

STUDY OBJECTIVES: (1) To determine the incidence of expiratory flow limitation (FL) at ICU admission, at the time of extubation, and at ICU discharge in intubated patients with COPD receiving mechanical ventilation for acute respiratory failure (ARF); and (2) to assess the feasibility of inspiratory capacity (IC) as an indication of pulmonary dynamic hyperinflation in this setting. DESIGN: Prospective, observational pilot study with physiologic measurements performed at ICU admission and during the weaning process driven by the clinician. A 60-min T-tube trial was initiated once criteria for weaning were present. The decision to extubate or reventilate patients was made by the clinician at the end of this session. Assessment of failure or success of T-tube trials was performed independently. SETTING: A 25-bed ICU of a tertiary teaching university hospital. PATIENTS: Over a 13-month period, 25 intubated patients with COPD receiving mechanical ventilation for ARF were included. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: At ICU admission, FL assessed by the negative expiratory pressure test was measured under passive ventilatory conditions at the baseline ventilatory settings, on zero end-expiratory pressure, and in a semirecumbent position. During weaning, FL, respiratory pattern, and IC were measured during T-tube trials, before extubation, 1 h after extubation, and at ICU discharge. At ICU admission, 24 of 25 patients presented FL with, on average, 73 +/- 22% of the tidal volume. Ten patients were unavailable for follow-up due to death (n = 6) unplanned extubation (n = 3), or refusal (n = 1), so that only 15 patients completed the whole protocol (all 15 patients were extubated). For these 15 patients, the incidence of FL was 93% at ICU admission, 47% before extubation, and 40% at ICU discharge. IC was significantly greater at ICU discharge than before extubation (36 +/- 11% predicted vs 44 +/- 12% predicted, p < 0.01) and in successful T-tube trials compared with unsuccessful T-tube trials (38 +/- 13% predicted vs 24 +/- 8% predicted, p < 0.01). CONCLUSIONS: The incidence of expiratory FL is high in patients with COPD receiving mechanical ventilation, and is reduced during aggressive therapy when the patient is placed on mechanical ventilatory support and the time that weaning begins during the ICU stay. IC was lower in patients in whom weaning was unsuccessful. Further large-scale studies are required to confirm these preliminary results.     

探讨浅快呼吸指数指导COPD患者撤机的临床价值

目的评价浅快呼吸指数（rapid-shallow-breathing index,RSBI）作为COPD患者撤机的临床价值。方法呼吸重症监护病房的20例机械通气的COPD患者,均通过了1h的自主呼吸实验（spontaneous breathing trial,SBT）。记录两个时期的RS-BI：SBT前、SBT1h。同时记录年龄、性别、APACHEⅡ（acute physiology and chronic health evaluationⅡ）评分、撤机前的动脉血气分析。结果 16例COPD患者成功撤机,4例患者撤机失败。在成功和失败两组间年龄、性别、APACHEⅡ评分无明显差异（P〉0.05）,PaCO2（partial pressure of carbon dioxide in arterial blood）有明显差异（P〈0.05）。以RSBI≤105bpm/L为标准预测撤机成功的灵敏度和特异度分别为：SBT前RSBI93.8%、10%;SBT1h的RSBI93.8%、45.5%。SBT1h的RSBI与PaCO2联合预测撤机成功的灵敏度为89.5%,特异度为78%。结论 SBT1h的RSBI预测COPD患者成功撤机的准确性高于SBT前,其与PaCO2联合评价将提高预测撤机成功的准确性。     

中心静脉血氧饱和度对困难脱机病人拔管失败预测价值的临床研究简

目的 探讨中心静脉血氧饱和度（ScvO2）对困难脱机病人拔管失败的预测价值.方法机械通气超过48 h的困难脱机病人,其中成功经历两步脱机策略后给予拔除气管插管的病人入选为进一步的研究对象.拔管失败定义为在48 h内需要重新插管.根据定义进一步分为拔管成功（ES）组和拔管失败（EF）组,测量病人自主呼吸试验（SBT）前1 min及后30 min的各项参数.结果 再插管率为32%.ScvO2的ROC曲线分析显示SBT开始后30 min,ScvO2下降5.4%,敏感性93%,特异性88%.结论 ScvO2是困难脱机病人拔管失败的一个早期的预测因子,下降5.4%以上可作为预测阈值.     

Association between angiotensin-converting enzyme gene polymorphisms and exercise performance in patients with COPD

Background and objective:   Recent studies have shown that polymorphisms of the angiotensin-converting enzyme (ACE) gene are closely associated with pulmonary disorders. The ACE gene is involved in the regulation of inflammatory reactions to lung injury, respiratory drive, erythropoiesis and tissue oxygenation. The hypothesis for this study was that the ACE gene may be associated with the ventilatory response to exercise and the aerobic work efficiency of skeletal muscle in patients with COPD.
Methods:   Sixty-one Chinese Han COPD patients and 57 healthy control subjects performed incremental cardiopulmonary exercise testing on a cycle ergometer. ACE genotypes were determined using PCR amplification.
Results:   Resting lung function and blood gas index were not significantly different among the three ACE genotype COPD groups. Similarly, there were no significant differences in AT, maximal O₂ uptake, maximal O₂ pulse, maximal dyspnoea index, ventilatory response (ΔVE/ΔVCO₂), O₂ cost of ventilation (VO₂/W/VE), end-tidal partial pressure of carbon dioxide at maximal exercise and maximal SaO₂ among the three ACE genotype COPD patients. Maximal work load and aerobic work efficiency were higher in the COPD group with the II genotype than in those with the ID or DD genotype. There were no significant differences in resting lung function and cardiopulmonary exercise testing parameters among the three ACE genotype control groups.
Conclusions:   The ACE gene may be involved in the regulation of skeletal muscle aerobic work efficiency, but is not associated with the ventilatory responses to exercise in COPD patients.     

Comparison of α-1-Antitrypsin and α-1-Antichymotpsin in Hepatocellular Carcinoma: An Immunoperoxidase Study

α-1-antitrypsin (A₁AT) has been shown to he a useful tumor marker for hepatocellular carcinoma (HCC) and some other neoplasms. No studies of α-1-antichymotrypsin (A₁AChy) in HCC have been reported. A comparative study of A₁AT and A₁AChy in HCC was undertaken. While 19/33 HCC were positive for A₁AT, all 33 HCC contained immunoreactive A₁AChy. Cells showing positive immunoreaction for both A₁AT and A₁AChy were more numerous in moderately differentiated HCC than in well differentiated or poorly differentiated HCC. Although the pattern of staining with both antisera was similar, in cases showing positive staining for both antisera, A₁AChy-positive cells were more numerous than A₁AT-positive cells. The results suggest a useful role for A₁AChy as a marker of HCC.     

Ultrasonographic evaluation of liver/spleen movements and extubation outcome

INTRODUCTION: The diaphragm plays a pivotal role in weaning and successful extubation. We hypothesized that ultrasonographic evaluation of the movements of the diaphragm by measuring liver/spleen displacement during spontaneous breathing trials is a good predictor for extubation outcome. PATIENTS AND METHODS: The studied subjects were intubated patients receiving mechanical ventilation who were scheduled to be extubated. The displacement of liver/spleen was measured by ultrasonography before extubation. The patients were classified into a success group (SG) or failure group according to the extubation outcome. The baseline data and organ displacements in these two groups were analyzed. The sensitivity and specificity for the mean organ displacements and weaning parameters to predict successful extubation were calculated. RESULTS: We included 55 patients, 32 of whom (58%) were in the SG. The baseline data are similar for these two groups, but the mean values of liver and spleen displacements were higher in the SG. Using a cutoff value of 1.1 cm, the sensitivity and specificity to predict successful extubation were 84.4% and 82.6%, respectively, better than traditional weaning parameters in this study. CONCLUSION: The displacement of the liver/spleen, measured by ultrasonography, is a good predictor for extubation outcome.     

Mini-Dose (1-μCi) 14-Urea Breath Test for the Detection of Helicobacter pylori

Objectives: To develop and evaluate a mini-dose (1-μ Ci ) ¹⁴C-urea breath test (UBT), using a simplified protocol. Methods: Fasting patients (n = 95) were given a drink of 1 μCi (37 kBq) of ¹⁴C-urea. Samples of breath carbon dioxide (2 mmol) were collected at 10, 20, and 30 min later by trapping in hyamine solution; ¹⁴C activity was measured by liquid scintillation counting. Results were expressed as "CO₂ recovery," i.e ., [(% of administered dose recovered/mmol CO₂ trapped) × body weight (kg)]. Reproducibility of the test was assessed by repeat studies on two consecutive days in 11 volunteers. All breath test results were compared with culture for Helicobacter pylori . In 27 patients, results also were compared with ¹³C-urea breath test (European protocol). Results: Using receiver operator characteristic (ROC) analysis, we selected a cut-off value of 0.55 at 20 min to separate those positive and negative for H. pylori . Sensitivity and specificity were 98% and 87%, respectively. Among four patients with negative culture hut positive ¹⁴C-breath tests, three had evidence of infection by serology or ¹³C-UBT. Assuming that these three were genuinely positive, the recalculated specificity improved to 97%, sensitivity remaining at 98%. The reproducibility of the test was good, with only a minor day-to-day variation. Concordance with the ¹³C-UBT was excellent: there was 100% agreement in the diagnostic classification of all 27 patients (19 positive, eight negative). Conclusions: The mini-dose ¹⁴C-urea breath test has a high diagnostic accuracy (sensitivity 98%, specificity 97%) with minimal radiation exposure. It is simple, rapid, and convenient for a busy general hospital.     

SBT联合BNP监测对COPD患者拔管结局的预测价值

目的探讨自主呼吸试验(SBT)联合脑钠肽(BNP)预测慢性阻塞性肺疾病(COPD)患者拔管结局价值.方法选择2016年1月至2018年12月广东同江医院重症监护室收治的需要行有创机械通气的COPD呼吸衰竭患者80例,根据最终成功拔管与否分为拔管成功组和拔管失败组.分别记录SBT试验前及通过SBT试验2h后患者BNP、血气分析结果,比较SBT前后BNP差值△BNP和△BNP的受试者工作特征曲线及曲线下面积.结果(1)SBT前,2组BNP水平差异无统计学意义(t=0.040,P>0.05),SBT后,拔管失败组BNP水平高于拔管成功组(t=23.458,P<0.05).(2)SBT前,2组pH、动脉血二氧化碳分压、动脉血氧分压差异均无统计学意义(t=1.030、0.481、0.585,P值均>0.05),SBT后,拔管失败组pH、动脉血氧分压低于拔管成功组(t=5.678、2.012,P值均<0.05),动脉血二氧化碳分压高于拔管成功组(t=5.098,P<0.05).(3)△BNP AUC大于SBT前BNP和SBT后BNP,△BNP的cut-off值为45 ng/L,特异度为95.66%,敏感度为83.32%,预测脱机后拔管失败准确率为93.11%.结论对于COPD合并心功能不全患者,达到撤机标准后,在进行SBT基础上评价SBT前后△BNP水平可有效预测COPD合并心功能不全患者撤机拔管成功率,可在临床广泛推广使用.     

Clearance from Plasma and Excretion in Urine, Faeces and Bile of an Intravenous Dose of Tritiated Vitamin K1 in Man

Vitamin K₁-³H (1 mg; 12 μCi) was injected intravenously into three normal men, into three patients undergoing duodenal intubation and into a patient with T-tube drainage of the common bile duct. In the normal subjects lipid-soluble radioactivity (representing the injected vitamin K₁-³H) disappeared rapidly from the plasma: the clearance curve for the first 6 hr could be resolved graphically into two exponential functions, the first with a T ® of 20–24 min and the second with a T ® of 121–150 min: water-soluble radioactivity, presumed to be metabolic products, appeared in the plasma within 30 min after injection, reached a peak at 2 hr and remained near this level for 24 hr. Of the injected radioactivity in the normal subjects, 19–26% was recovered in the urine after 3 days and 34–38% in the faeces after 5 days: most of the radioactive material in the faeces was lipid-soluble, which on thin-layer chromatography had a polarity between that of vitamin K₁ and vitamin K₁γ-lactone. In the patients undergoing duodenal intubation, radioactivity was detected in the duodenal juice within 20–40 min after injection of vitamin K₁-³H. Radioactivity was also detected in the bile in the patient with T-tube drainage of the common bile duct. Most of the radioactivity in the duodenal juice and bile was water-soluble. It seems likely that the radioactivity appearing in the faeces after intravenous injection of vitamin K₁-³H is derived from biliary excretion of water-soluble conjugated metabolites which become lipid-soluble by decon-jugation during their passage through the bowel.     

Non-invasive ventilation improves peripheral oxygen saturation and reduces fatigability of quadriceps in patients with COPD

Background and objective:   Non-invasive ventilation (NIV) might improve peripheral muscle function and exercise capacity in severely disabled patients. This study evaluated the physiological impact of NIV on isokinetic concentric strength and endurance of lower limb muscles in patients with severe COPD.
Methods:   This clinical trial tested COPD patients ( n  = 24) and healthy subjects ( n  = 18). Subjects underwent isokinetic dynamometry tests while given either bi-level positive airway pressure ventilation (BV) or sham ventilation (SV), in a randomized order with 30 min of rest prior to each intervention. The inspiratory level of BV was set up to 14 cm H₂O and expiratory pressure up to 6 cm H₂O. Peripheral oxygen saturation (SpO₂), heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP) at the peak of exercise were measured for each intervention.
Results:   Compared with controls, COPD patients had lower values of SpO₂ and HR ( P  < 0.01) during both BV and SV and lower values of DBP ( P  < 0.01) during BV. BV improved SpO₂ ( P  < 0.01), and reduced SBP in both COPD ( P  < 0.01) and control groups ( P  < 0.05) and reduced DBP in COPD patients ( P  < 0.01). BV also reduced the fatigue index in COPD patients when compared with SV ( P  = 0.003). Variation (BV-SV) of total work at the peak of the test was higher in the control group than in the COPD group ( P  < 0.05).
Conclusions:   BV improved SpO₂ and reduced the fatigability of the quadriceps muscle in patients with severe COPD. These results support the need for further evaluation of BV as adjunct during high-intensity strength exercise training in these patients.     

Cough-reflex sensitivity to inhaled capsaicin in COPD associated with increased exacerbation frequency

Background and objective:   The causes of exacerbations in COPD patients are poorly understood. This study examined the association between cough-reflex sensitivity in patients with stable COPD and the frequency of subsequent exacerbations.
Methods:   The sampling frame for cases and controls for this study was patients attending a hospital outpatient clinic. cough-reflex sensitivity was evaluated using the log concentration of capsaicin causing five or more coughs (log C₅). Subsequent COPD exacerbations were identified prospectively via symptom-based diaries over a 12-month period.
Results:   The study group comprised 45 COPD subjects and 10 controls. Mean log C₅ was lower in the COPD group than in the control group (0.97 (95% confidence interval (CI): 0.76–1.18) versus 1.26 (95% CI: 0.81–1.71), P  = 0.095). In the COPD group, log C₅ was negatively correlated with serum CRP level ( r  = −0.36, P  = 0.02) and significantly associated with the exacerbation frequency ( r  = −0.38, P  = 0.01). Stepwise multiple regression analysis showed that cough-reflex sensitivity was significantly associated with exacerbation frequency ( r ² = 0.15, P  = 0.01).
Conclusions:   Hypersensitivity of the cough reflex to inhaled capsaicin might reflect airway inflammation in stable COPD patients, which predisposes to frequent exacerbations.     

Irradiated Blood Platelet Concentrates Stored for Five Days -Evaluation by in vitro Tests

Abstract. Platelet concentrates, irradiated with 15 Gy and stored for 5 days at room temperature under standardized conditions, were evaluated by in vitro tests and electron microscopy, in a paired study with nonirradiated platelets from the same concentrates, to investigate their usefulness for transfusion. The results showed no significant differences between the two groups in pH, pO₂, PCO₂, in vitro platelet aggregation, LDH, β-thromboglobulin and thromboxane-B₂. Examination by electron microscopy showed a higher degree of degranulation in the 5-day-old platelets but no certain difference between irradiated versus nonirradiated platelets. On the basis of satisfactory in vitro storage properties, platelet concentrates can be stored for 5 days in PL-1240 bags after irradiation. However, we recommend irradiation just before transfusion whenever possible.     

Effects of Alcohol on Intrauterine Oxygen Tension in the Rat

The effects of alcohol on the availability of oxygen within the uterine lumen of rats were determined on Day 4 of pseudopregnancy. Intraluminal oxygen tension (pO₂) was measured in vivo in anesthetized rats using a 22-gauge polarographic oxygen sensor. Intrauterine pO₂ was measured for 15 min before and after intravenous injection of alcohol (1.0 g/kg: 100% ethanol/saline, 1:2 v/v) or vehicle (physiological saline). Alcohol administration increased mean intrauterine pO₂ (mm Hg) from a pretreatment level of 28.3 ± 2.8 to 38.7 ± 3.8 mm Hg ( p < 0.05, n = 10) at 15 min postinjection. The rapid rise in oxygen tension was accompanied by increased frequency of fluctuation (peaks/hr) in intraluminal pO₂ (prealcohol: 64.2 ± 8.8 vs. postalcohol 96.0 ± 7.7 peaks/hr; ( p < 0.05, n = 10). Injection of saline did not alter any aspect of intrauterine pO₂. During the period of measurement of luminal pO₂, blood alcohol levels increased from 0 during pretreatment to 106 mg% within 10 min of injection. These results indicate that alcohol increases the availability of oxygen within the uterus during the time of endometrial sensitivity to deciduogenic stimuli and blastocyst implantation.     

无创通气在慢性阻塞性肺疾病患者撤机中的应用

目的：探讨无创通气应用于慢性阻塞性肺疾病（COPD）患者有创机械通气撤机中的作用。方法：62例cOPD合并呼吸衰竭应用有创通气后撤机拔管的患者，分为治疗组32例，对照组30例，治疗组在常规药物治疗基础上应用无创通气，对照组应用常规治疗（药物治疗＋吸氧）。观察两组的血气分析指标、再插管率、住院天数及住院病死率等。结果：治疗组给予无创通气后与对照组比较动脉血气PaO2明显上升（P〈0．05），PaCO2下降明显（P〈0．05），两组再插管率为9%和30％（P〈0．05），住院天数为（32±10）d和（38±15）d（P〈0．05），住院病死率为6．2％和23．3％（P〈0．05）。结论：撤机拔管后立即开始应用无创通气的患者再插管率下降，住院天数减少及病死率下降。     

Preoperative use of inhaled tiotropium in lung cancer patients with untreated COPD

Background and objective:   Lung cancer patients with COPD are at high risk during surgery. Tiotropium, a long-acting bronchodilator, is a preferred maintenance therapy for COPD, but its efficacy in the perioperative period has not been clarified.
Methods:   A retrospective review was performed of the medical records of 102 patients with primary lung cancer and COPD, who underwent scheduled surgery. Twenty-one lung cancer patients with untreated mild-to-severe COPD received tiotropium preoperatively. Spirometry was performed prior to and after 2 weeks of treatment with tiotropium, and at 3 months after surgery.
Results:   Two-week preoperative treatment with tiotropium significantly improved respiratory symptoms and pulmonary function as reflected by FVC (median 3.43 L pretreatment vs 3.52 L post-treatment), FEV₁ (median 2.06 L vs 2.32 L) and FEV₁% (73.2% vs 81.0%) (all P  < 0.001). Postoperative FEV₁% was significantly increased from a median of 56.0% (interquartile range 51.6–60.3) to 63.4% (60.8–66.0) ( P  < 0.001). The increase in FEV₁ was inversely associated with severity of COPD ( r  = −0.59, P  < 0.005). Lung resections were successfully accomplished without complications. The postoperative FEV₁ predicted prior to tiotropium treatment was underestimated (median predicted postoperative FEV₁ 1.65 L vs median measured postoperative FEV₁ 1.96 L, P  < 0.001).
Conclusions:   Preoperative treatment with tiotropium may facilitate surgical treatment for lung cancer patients with COPD. This is encouraging for COPD patients who may require curative lung resections.     

单一剂量右美托咪定在慢性阻塞性肺病患者撤机中的应用

目的:研究应用单一剂量右美托咪定对慢性阻塞性肺病(COPD)患者拔除气管插管期间的影响。方法:选择COPD合并呼吸衰竭经呼吸机治疗后欲拔除气管插管的40例患者,分为观察组和对照组,各20例。观察组患者拔管前予以0.5μg/kg负荷剂量的右美托咪定,10min注射完毕后开始拔管。监测并记录2组患者用药前(T0)、拔管前(T1)、吸痰后(T2)、拔管后(T3)、拔管后5min(T4)、拔管后10min(T5)、拔管后30min(T6)的呼吸、心率、收缩压、动脉血二氧化碳分压(PaCO2)、氧分压(PaO2)和24h内重插管上机例数。结果:2组患者用药前一般资料和生命体征及血气之间无显著差异;用药导致观察组患者SBP、HR下降,但不影响RR、PaCO2、PaO2;此剂量用药不能完全抑制拔管时吸痰所造成的交感兴奋,但可以减轻幅度,减少再插管率。结论:0.5μg/kg负荷剂量的右美托咪定用于COPD患者脱机时拔管,心血管稳定性较好,在不影响患者呼吸的前提下,有效减轻患者拔管时的血流动力学剧烈变化和继发的二氧化碳潴留及低氧血症,并可能减少由此引发的脱机失败。     

Effect of Filtration on Subsequently Stored Platelet Concentrates

The effect of filtration on the quality of platelet concentrates (PC) during storage was investigated. Two leukocyte depletion filters (Pall PL50HF and Sepacell PL-10A) were applied to filter PC made from a pool of 4 buffy coats. For each experiment 3 PC were pooled and divided into 3 identical PC to eliminate differences between the PC. Two PC were filtered, and the third PC served as an unfiltered control. A total of 12 experiments was performed. Before filtration, volumes of the PC were 263±11.7 ml (mean±SD). Platelet and leukocyte counts per PC were 241±25.9 times 10⁹ and 7.2±1.8 times 10⁶, respectively. After filtration leukocyte counts did not exceed 5 times 10⁴ in any of the PC. In the PC filtered with the Pall PL50HF the mean platelet loss was approximately 14% and with the Sepacell PL-10A, 17%. During a 9-day storage period the pH, PO₂, PCO₂, bicarbonate, lactate and glucose concentration and LDH release as well as the morphology, examined by the swirling effect and microscopically, were not significantly different in filtered and unfiltered units. Filtration through the 2 investigated leukocyte depletion filters for PC did not adversely affect in vitro viability of the platelets during storage.     

PEDIATRICS

Eduardo Ibarguen-Secchia , MD. *   * Pediatric Digestive Care, San Antonio, TX.
Purpose: To determine safety, tolerability and comfort of use of carbon dioxide for insufflation during colonoscopy in children.
Methods: After informed consent, a total of 84 consecutive patients undergoing colonoscopy were randomized to use either air or CO₂ insufflation. Ages ranged from 6 years to 16 years (mean 12). End tidal carbon dioxide was recorded before the examination, at 2 minute intervals during the examination and 10 minutes after it. General anesthesia was used for sedation in all cases. Pain at 5 and 15 minutes after the procedure was measured using a ten-point analog scale.
Results: Pain scores at 5 minutes after the examination were 5.2 ± 0.3 for the air group and 4.8 ± 0.2 for the CO₂ group (no significant difference). At 15 minutes the score were 2.8 ± 0.3 for the air group and 0.7 ± 0.3 for the CO₂ group (significant at P < 0.05). End tidal CO₂ in both groups was no different.
Conclusion: Using CO₂ for insufflation during colonoscopy is safe and improves patient comfort. Patients who received CO₂ insufflation during their colonoscopy experienced less post-procedure discomfort. There was no evidence of CO₂ retention based on end tidal carbon dioxide monitoring.     

Mercury compounds induce a rapid increase in procoagulant activity of monocyte-like U937 cells

. When monocytic leukaemia line U937 cells were incubated in the presence of HgCl₂ there was a rapid increase in tissue factor (TF)-dependent procoagulant activity, reaching a maximum (equivalent to the total TF activity observed when cells had been subjected to a freeze/thaw cycle) after 15 min at 50 μ m HgCl₂ and after 30 min at 10 μ m HgCl₂. Two other heavy metal compounds, AgNO₃ and phenylmercuric acetate, caused a similar increase in TF activity. The increase was independent of protein synthesis. Other reagents tested, CdCl₂, ZnCl₂, NiCl₂, ADP, FMLP and monocyte chemotactic factor (MCF-1), did not cause a rapid increase in functional activity, when tested under the same experimental conditions. The addition of HgCl₂ to the cells causes, in a concentration-dependent manner, a 10-12-fold increase in intracellular calcium (Ca_i) which coinicides with increase in TF activity. Calcium ionophore also caused an increase in TF activity of the U937 cells. Upon treatment with HgCl₂ the cells surface of U937 cells showed a large increase in the level of phosphatidylserine (PS) on the cell surface (as measured by potentiation of the rate of activation of prothrombin by factor Xa-factor Va) but with no change in the level of TF antigen on the cell surface. We consider that the TF is present on the cell surface of the monocyte but relatively inactive towards the physiological substrate, factor X (FX), until HgCl₂ causes a change in the polarity of the cell membrane exposing PS on the outer leaflet by a mechanism likely to be enhanced by the increase in intracellular calcium.     

Analysis of Heat-damaged Erythrocyte Clearance Curves

S ummary . The rate of clearance from the blood of heat-damaged erythrocytes (HDE) is used routinely as a quantitative assessment of splenic function. The time taken for the value at 3 min to fall by 50% ( t _0-5) is usually taken as the index of function. The clearance of HDE is dependent on three processes: splenic blood flow, splenic HDE extraction ratio and intrasplenic transit time of 'unextracted'HDE, returning to the circulation. Exponential analysis of the clearance curve can resolve these three functions. Simple methods of analysis, however, such as t _0-5, which are applied directly to the curve, may be weighted in favour of any one of them. In this paper, a large number of clearance curves have been analysed and the components of splenic function resolved. The t _0-5, the percentage fall in HDE between 8 and 28 min ( C ₂₀), the rate constant at 8 min ( K ₈) and the rate constant of the tail of the curve (α₂) have been correlated with these components. K ₈ showed a close correlation with splenic blood flow, and α₂ with the rate of HDE phagocytosis. In general, the correlation between the various components of splenic function was better with C ₂₀ than with t _0-5. This is explained predominantly by the fact that the t _0-5 includes liver clearance. The t _0-5 should therefore be used with caution as an estimate of splenic function, which can be usefully assessed by applying alternative simple methods of analysis described.