Effectiveness of Selected Air Cleaning Devices During Dental Procedures.

INTRODUCTION: The recent COVID-19 pandemic has underscored the necessity of protecting health care providers (HCPs) against the transmission of infectious agents during dental procedures. To this end, the effectiveness of several air cleaning devices (ACDs) in reducing HCPs exposure to aerosols generated during dental procedures was estimated, separately or in combination with each other. These ACDs were a chairside unit capturing aerosols at the source of generation, and four ambient ACDs: a portable ambient ACD; a negative pressure module; a custom made, fan-operated and wall-mounted air filter (WMAF); and a smaller and passive version of the latter. The last three ACDs were intended for mobile dental clinics (MDCs) only. MATERIALS AND METHODS: This assessment was performed in two different environments: in a dental clinic operatory and in a MDC. Two dental personnel, acting in the roles of dentist and dental assistant, performed on simulated patient aerosol-generating and non-aerosol-generating procedures. For each 5-minute scenario, the cumulative exposure to airborne particulate matter 10 µm in size or smaller (PM10) was determined by calculating the sum of all 1 second readings obtained with personal and ambient air monitors. The effectiveness of the ACDs in capturing PM10 was estimated based on the capability of the ACDs to keep PM10 level at or below the initial background level. RESULTS: In all conditions assessed in the dental clinic operatory, when both the chairside and portable ambient ACDs were functioning, an estimated effectiveness of 100% in capturing PM10 was achieved. In the MDC, in all conditions where the chairside ACD was used without the negative pressure module, an estimated effectiveness of 100% was also achieved. The simultaneous operation of the negative pressure module in the MDC, which led to a room negative pressure of -0.25 inch wc, reduced the chairside ACD's effectiveness in capturing aerosols. Conversely, the use of the WMAF in the MDC in combination with the chairside ACD further reduced exposure to PM10 below the initial background level. Nonetheless, in all conditions assessed in both settings (dental clinic operatory and MDC), larger visible aerosols were produced, often landing on the surrounding environment. A fair portion of these aerosols landed on the inside of the chairside ACD flange. CONCLUSIONS: This assessment suggests that the use of the tested chairside ACD, by capturing aerosols at the source of generation, had the greatest impact on reducing exposure of dental personnel to PM10 produced during dental procedures. This study also indicates that such exposure is further reduced with the addition of an ambient ACD. However, creating a negative pressure room as high as -0.25 inch wc can lead to air turbulence reducing the effectiveness of ACDs in capturing aerosols at the source. Furthermore, the presence of uncaptured droplets and spatter on the surrounding environment supports the need to complement the use of engineering controls with proper administrative controls and personal protective equipment, as recommended by governmental agencies and the scientific community for preventing the transmission of infection in health care settings.

Self-driving laboratory for accelerated discovery of thin-film materials.

Discovering and optimizing commercially viable materials for clean energy applications typically takes more than a decade. Self-driving laboratories that iteratively design, execute, and learn from materials science experiments in a fully autonomous loop present an opportunity to accelerate this research process. We report here a modular robotic platform driven by a model-based optimization algorithm capable of autonomously optimizing the optical and electronic properties of thin-film materials by modifying the film composition and processing conditions. We demonstrate the power of this platform by using it to maximize the hole mobility of organic hole transport materials commonly used in perovskite solar cells and consumer electronics. This demonstration highlights the possibilities of using autonomous laboratories to discover organic and inorganic materials relevant to materials sciences and clean energy technologies.

Pharmacological and toxicological activity of RSD921, a novel sodium channel blocker.

BACKGROUND: RSD921, the R,R enantiomer of the kappa (k) agonist PD117,302, lacks significant activity on opioid receptors. METHODS: The pharmacological and toxicological actions were studied with reference to cardiovascular, cardiac, antiarrhythmic, toxic and local anaesthetic activity. RESULTS: In rats, dogs and baboons, RSD921 dose-dependently reduced blood pressure and heart rate. In a manner consistent with sodium channel blockade it prolonged the PR and QRS intervals of the ECG. Furthermore, in rats and NHP, RSD921 increased the threshold currents for induction of extra-systoles and ventricular fibrillation (VFt), and prolonged effective refractory period (ERP). In rats, RSD921 was protective against arrhythmias induced by electrical stimulation and coronary artery occlusion. Application of RSD921 to voltage-clamped rat cardiac myocytes blocked sodium currents. RSD921 also blocked transient (ito) and sustained (IKsus) outward potassium currents, albeit with reduced potency relative to sodium current blockade. Sodium channel blockade due to RSD921 in myocytes and isolated hearts was enhanced under ischaemic conditions (low pH and high extracellular potassium concentration). When tested on the cardiac, neuronal and skeletal muscle forms of sodium channels expressed in Xenopus laevis oocytes, RSD921 produced equipotent tonic block of sodium currents, enhanced channel block at reduced pH (6.4) and marked use-dependent block of the cardiac isoform. RSD921 had limited but quantifiable effects in subacute toxicology studies in rats and dogs. Pharmacokinetic analyses were performed in baboons. Plasma concentrations producing cardiac actions in vivo after intravenous administration of RSD921 were similar to the concentrations effective in the in vitro assays utilized. CONCLUSIONS: RSD921 primarily blocks sodium currents, and possesses antiarrhythmic and local anaesthetic activity.

The lipid transfer activity of phosphatidylinositol transfer protein is sufficient to account for enhanced phospholipase C activity in turkey erythrocyte ghosts.

BACKGROUND: The minor membrane phospholipid phosphatidylinositol 4, 5-bisphosphate (PIP2) has been implicated in the control of a number of cellular processes. Efficient synthesis of this lipid from phosphatidylinositol has been proposed to require the presence of a phosphatidylinositol/phosphatidylcholine transfer protein (PITP), which transfers phosphatidylinositol and phosphatidylcholine between membranes, but the mechanism by which PITP exerts its effects is currently unknown. The simplest hypothesis is that PITP replenishes agonist-sensitive pools of inositol lipids by transferring phosphatidylinositol from its site of synthesis to sites of consumption. Recent cellular studies, however, led to the proposal that PITP may play a more active role as a co-factor which stimulates the activity of phosphoinositide kinases and phospholipase C (PLC) by presenting protein-bound lipid substrates to these enzymes. We have exploited turkey erythrocyte membranes as a model system in which it has proved possible to distinguish between the above hypotheses of PITP function. RESULTS: In turkey erythrocyte ghosts, agonist-stimulated PIP2 hydrolysis is initially rapid, but it declines and reaches a plateau when approximately 15% of the phosphatidylinositol has been consumed. PITP did not affect the initial rate of PIP2 hydrolysis, but greatly prolonged the linear phase of PLC activity until at least 70% of phosphatidylinositol was consumed. PITP did not enhance the initial rate of phosphatidylinositol 4-kinase activity but did increase the unstimulated steady-state levels of both phosphatidylinositol 4-phosphate and PIP2 by a catalytic mechanism, because the amount of polyphosphoinositides synthesized greatly exceeded the molar amount of PITP in the assay. Furthermore, when polyphosphoinositide synthesis was allowed to proceed in the presence of exogenous PITP, after washing ghosts to remove PITP before activation of PLC, enhanced inositol phosphate production was observed, whether or not PITP was present in the subsequent PLC assay. CONCLUSION: PITP acts by catalytically transferring phosphatidylinositol down a chemical gradient which is created as a result of the depletion of phosphatidylinositol at its site of use by the concerted actions of the phosphoinositide kinases and PLC. PITP is therefore not a co-factor for the phosphoinositide-metabolizing enzymes present in turkey erythrocyte ghosts.

High-temperature high-pressure calorimeter for studying gram-scale heterogeneous chemical reactions.

We present an instrument for measuring pressure changes and heat flows of physical and chemical processes occurring in gram-scale solid samples under high pressures of reactive gases. Operation is demonstrated at 1232 °C under 33 bars of pure hydrogen. Calorimetric heat flow is inferred using a grey-box non-linear lumped-element heat transfer model of the instrument. Using an electrical calibration heater to deliver 900 J/1 W pulses at the sample position, we demonstrate a dynamic calorimetric power resolution of 50 mW when an 80-s moving average is applied to the signal. Integration of the power signal showed that the 900 J pulse energy could be measured with an average accuracy of 6.35% or better over the temperature range 150-1100 °C. This instrument is appropriate for the study of high-temperature metal hydride materials for thermochemical energy storage.

Acoustic buffeting by infrasound in a low vibration facility.

Measurement instruments and fabrication tools with spatial resolution on the atomic scale require facilities that mitigate the impact of vibration sources in the environment. One approach to protection from vibration in a building's foundation is to place the instrument on a massive inertia block, supported on pneumatic isolators. This opens the questions of whether or not a massive floating block is susceptible to acoustic forces, and how to mitigate the effects of any such acoustic buffeting. Here this is investigated with quantitative measurements of vibrations and sound pressure, together with finite element modeling. It is shown that a particular concern, even in a facility with multiple acoustic enclosures, is the excitation of the lowest fundamental acoustic modes of the room by infrasound in the low tens of Hz range, and the efficient coupling of the fundamental room modes to a large inertia block centered in the room.

Thrombosis in the emergency department: use of a clinical diagnosis model to safely avoid the need for urgent radiological investigation.

CONTEXT: The management of patients presenting to hospital emergency departments with suspected deep vein thrombosis (DVT) is problematic because urgent diagnostic imaging capability is sometimes unavailable. Experienced physicians using clinical skills alone can classify patients with suspected DVT into low-, moderate-, and high-probability categories. OBJECTIVES: To determine the accuracy of an explicit clinical model for the diagnosis of DVT when applied by emergency department physicians and to assess the safety and feasibility of a management strategy based on the clinical pretest probability for patients presenting to the emergency department with suspected DVT outside of regular hospital staff work hours. METHODS: A prospective cohort study was performed in the emergency departments of 2 tertiary care institutions involving 344 patients with suspected DVT. Patient conditions were evaluated by an emergency department physician who determined the pretest probability for DVT to be low, moderate, or high using an explicit clinical model. Patients for whom DVT was considered a low pretest probability were discharged from the emergency department and returned the following day for venous compression ultrasound imaging of the affected leg. Patients for whom DVT was considered a moderate pre-test probability received a single, weight-adjusted dose of subcutaneous unfractionated heparin sodium (between 12 500 and 20 000 U), were discharged from the emergency department, and returned the next morning to undergo ultrasonography. Patients for whom DVT was considered a high pretest probability were admitted to the hospital, administered intravenous unfractionated heparin, and ultrasonography was arranged within 24 hours. Patients with positive ultrasonographic findings were diagnosed with DVT, except for those with low pretest probability for whom confirmatory venography was performed. Patients with DVT excluded in the initial evaluation period did not receive anticoagulant therapy. All patients were followed up for 90 days to monitor development of thromboembolic or bleeding complications. RESULTS: Twenty-four (49.0% [95% confidence interval (CI), 34.5%-63.6%]) of 49 patients in the high-probability category, 15 (14.3% [95% CI, 8.3%-22.4%]) of 105 in the moderate-, and 6 (3.2% [95% CI, 1.2%-6.7%]) of 190 in the low-probability category were confirmed to have DVT. Overall, 45 (13.1%) of 344 patients were confirmed to have DVT. No patient developed pulmonary embolism or major bleeding complications within 48 hours of initial evaluation in the emergency department. Of the 301 patients who had DVT excluded during the initial evaluation period, only 2 (0.7% [95% CI, 0.1%-2.3%]) developed venous thromboembolic complications (calf vein thromboses in both) in the 3-month follow-up period. CONCLUSIONS: Using an explicit clinical model, emergency department physicians can accurately classify patients with suspected DVT into high-, moderate-, and low-probability groups. A management plan based on probability for DVT that avoids the need for urgent diagnostic imaging is safe and feasible in the emergency department setting.

Group II metabotropic glutamate receptor antagonism prevents the antiallodynic effects of R-isovaline.

We previously showed that isovaline is a peripheral analgesic which acts in vivo and in brain slices as an atypical metabotropic GABA(B) agonist. Peripheral inhibitory group II and III metabotropic glutamate receptors (mGluRs) belong to the same family C as GABA(B) receptors; therefore, we hypothesized that isovaline's analgesic effects could include their activation. We examined the effects of R-isovaline on mechanical allodynia produced by prostaglandin E2 in the mouse paw. Subcutaneous R-isovaline produced dose-dependent antiallodynia restricted to the injected hindlimb. This antiallodynia was blocked by co-injection with a selective group II mGluR antagonist, LY341495, but not a group III mGluR antagonist (MAP-4). The antiallodynic effect of R-isovaline was potentiated by co-administration of a group II mGluR-positive allosteric modulator, LY487379. Injection of a group II mGluR agonist (LY354740) produced an antiallodynic effect which was completely reversed by group II antagonism, but was not affected by group III or GABA(B) (CGP35348) antagonism. Similarly, group II mGluR antagonism did not alter the antiallodynia produced by the prototypical GABA(B) agonist, baclofen. Hence, there was no apparent crosstalk between group II mGluRs and GABA(B) receptors. Previous studies have demonstrated that peripheral GABA(B) receptor activation by isovaline produces antiallodynia. In addition, the present results indicate that activation of peripheral group II mGluRs by R-isovaline produces antiallodynia.

RSD1019 suppresses ischaemia-induced monophasic action potential shortening and arrhythmias in anaesthetized rabbits.

The electrophysiological actions of lidocaine, tedisamil and RSD1019 were assessed on normal and ischaemic cardiac tissue using monophasic action potentials (MAPs) recorded from the epicardium of anaesthetized rabbits. Drug effects on ischaemia-induced arrhythmias were assessed simultaneously in the same rabbits. Lidocaine, infused at 2.5, 5 and 10 micromol kg(-1) min(-1) i.v., accelerated and worsened the electrophysiological derangement caused by ischaemia, had profibrillatory actions and reduced the time to the occurrence of ventricular fibrillation (VF) relative to controls. Tedisamil, infused at 0.063, 0.125 and 0.25 micromol kg(-1) min(-1) i.v., prolonged MAP duration at 90% repolarization (MAPD(90%)) before induction of ischaemia in a dose-related manner; however, this effect was not maintained 5 min after induction of ischaemia. Tedisamil had no significant antiarrhythmic actions over the dose-range tested. RSD1019, infused at 2, 4 and 8 micromol kg(-1) min(-1) i.v., produced a small increase in MAPD(90%) before induction of ischaemia and only at the highest dose tested. In contrast to tedisamil, RSD1019 suppressed ischaemia-induced MAP shortening assessed 5 min after induction of ischaemia. This effect was dose-related. RSD1019 completely prevented ischaemia-induced tachyarrhythmias at the mid and highest infusion levels tested. The results of this study illustrate a pathologically targeted approach for preventing ischaemia-induced arrhythmias. Suppression of ischaemia-induced MAP shortening, demonstrated herein for RSD1019, represents a novel antifibrillatory approach.

Effects of aspirin and prostacyclin on arrhythmias resulting from coronary artery ligation and on infarct size.

1 The effects of pretreatment with aspirin, and of prostacyclin (PGI(2)) infusions, on responses to myocardial ischaemia and infarction produced by ligation of a coronary artery were investigated in conscious rats.2 Surgical preparation, under halothane anaesthesia, consisted of implanting exteriorized aortic and jugular cannulae, ECG leads and a polypropylene/polyethylene occluder for the left anterior descending coronary artery. Ligation of the coronary artery was performed six to nine days after surgery.3 Aspirin pretreatment consisted of 100 mg/kg given intravenously 1 or 36 h before ligation. PGI(2) infusions (10-400 ng kg(-1) min(-1), i.v.) were begun 2 min before ligation and continued for 4 h afterwards.4 ECG, blood pressure, heart rate and arrhythmias were recorded starting 30 min before, and continuing for 4 h after, ligation. Twenty-four hours after ligation, in surviving animals, the heart was removed for estimation of occluded and infarcted zones.5 Some treatments provided antiarrhythmic and other protection in the first 30 min post-ligation. By 4 and 24 h post-ligation, protective effects were lost.6 Both aspirin pretreatment and low doses of prostacyclin reduced arrhythmias occurring within 30 min of ligation. The highest dose of prostacylin (400 ng kg(-1) min(-1)) was arrhythmogenic.7 None of the treatments influenced the amount of cardiac tissue occluded or infarcted by ligation.8 The conclusions from this study in conscious rats were that acute aspirin pretreatment and low doses of infused prostacyclin have limited beneficial actions which are mainly confined to the earliest post-ligation period.

The effects of ablations in the central nervous system on arrhythmias induced by coronary occlusion in the rat.

The role of the central nervous system (CNS) in arrhythmogenesis in the 4 h period following occlusion of a coronary artery was investigated in rats by use of CNS ablations and other procedures. Ablations in the CNS included pithing, spinalization and decerebration combined with acute and chronic surgical preparation and noradrenaline/adrenaline infusions. All procedures involving acute surgery reduced the incidence and severity of the arrhythmias induced by occlusion. Such reductions were most marked in the second (0.5-4 h post-occlusion) arrhythmic period. The observed reductions in arrhythmias could not be explained in terms of involvement of the CNS or adrenoceptor activation. When circulating leucocytes, platelets and serum potassium were measured in a group of pithed rats before and after occlusion, reduced levels (20-50%) of both leucocytes and platelets occurred while serum potassium levels rose by 50-100%. Arrhythmias following coronary occlusion may depend in part on factors in the blood such as leucocytes, platelets and serum potassium and these factors may be altered by acute surgery.

The antiarrhythmic efficacy of intravenous anipamil against occlusion and reperfusion arrhythmias.

1. Anipamil, a long acting analogue of verapamil, was tested for its actions against arrhythmias induced by ischaemia and reperfusion in conscious and anaesthetized rats, as well as for effects on epicardial intracellular action potentials. 2. When given 15 min or 4 h before coronary occlusion, 1 and 5 mg kg-1 anipamil reduced ischaemia-induced arrhythmias in conscious rats. The same doses also reduced arrhythmias when given 15 min before occlusion in acutely-prepared anaesthetized rats. ED50 values were between 1 and 5 mg kg-1. 3. The incidence of reperfusion arrhythmias depended upon the period of regional ischaemia prior to reperfusion such that the peak incidence occurred after 5-7 min of ischaemia. Anipamil (2.5 mg kg-1, i.v.) selectively abolished the reperfusion arrhythmias induced by short periods of ischaemia, although some antiarrhythmic effects were seen for all periods of ischaemia. 4. Anipamil slowed the rate of development of R-wave increases and S-T segment elevations induced by ischaemia, but did not reduce the maximum values they attained. 5. Anipamil (2.5 mg kg-1 i.v.) lacked Class I or III electrophysiological actions on intracellular action potentials recorded in vivo from the epicardium of rat hearts. 6. In conclusion, the antiarrhythmic actions of anipamil appeared to depend upon calcium antagonism which may have reduced arrhythmias by a combination of anti-ischaemic and direct anti-arrhythmic actions. Presumed anti-ischaemic actions changed the relationship between the duration of preceding ischaemia and resulting reperfusion arrhythmias.

Antiarrhythmic actions of verapamil against ischaemic arrhythmias in the rat.

The actions of intravenous verapamil against arrhythmias induced by occlusion of a coronary artery were investigated in conscious rats. Verapamil (2-20 mg kg-1, i.v. given pre-occlusion) dose-dependently reduced arrhythmias in rats with either large or small occluded zones at an ED50 of 6 mg kg-1. This dose was effective when given immediately post-occlusion. Severe arrhythmias, as opposed to PVC, were preferentially reduced. In conscious, and pentobarbitone-anaesthetized rats, verapamil (6 mg kg-1) had different effects on electrically-induced arrhythmias, and the ECG, from an equi-effective anti-arrhythmic dose of quinidine (20 mg kg-1, i.v.). Quinidine decreased following frequency, but increased threshold current and pulse width, whereas verapamil did not. Both drugs increased P-R interval, but only quinidine increased QRS and Q-T intervals. Thirty minutes post-occlusion, the verapamil content of tissue and blood was determined after a 6 mg kg-1 dose given pre- or post-occlusion. Measurable levels of verapamil were found in both normal and ischaemic myocardium. Plasma and plasma water concentrations were 3.6 +/- 0.8 mumol l-1 and 0.6 +/- 0.1 mumol l-1 (mean +/- s.e. mean), respectively following post-occlusion administration vs. 2.7 +/- 1.2 and 0.24 +/- 0.04 for pre-occlusion administration. Plasma water concentrations were close to IC50 values for inhibition of contractility in rat atria and ventricles. Similar concentrations depressed slow action potentials induced in rat ventricles by raised K+ We suggest that the ability of verapamil to prevent severe ventricular arrhythmias following myocardial ischaemia in the conscious rat is largely due to the calcium antagonist effects of the drug.

Antiarrhythmic properties of tedisamil (KC8857), a putative transient outward K+ current blocker.

1. Rats were used to evaluate the antiarrhythmic properties of tedisamil, a novel agent with the electrophysiological properties of a Class III antiarrhythmic drug. Tedisamil was tested against coronary artery occlusion-induced arrhythmias in conscious animals. 2. The actions of tedisamil on the ECG, as well as responses to electrical stimulation, were compared with those on the configuration of epicardial intracellular action potentials recorded in vivo. 3. Tedisamil (1-4 mg kg-1, i.v.) caused bradycardia, elevated blood pressure and dose-dependently reduced ventricular fibrillation (VF) induced by occlusion of the left anterior descending coronary artery. Other ischaemia-associated arrhythmias were not so well suppressed. Antiarrhythmic activity was greatest when the tedisamil-induced bradycardia was prevented by electrically-pacing the left ventricle. 4. Tedisamil dose-dependently lengthened the effective refractory period and prevented electrically-induced VF. In vivo, tedisamil (0.5-4 mg kg-1, i.v.) prolonged the duration of epicardial intracellular action potentials by up to 400%. 5. Results showed that tedisamil possessed antifibrillatory actions in rats that were related to Class III electrophysiological actions as revealed by electrical stimulation and electrophysiological analyses.

Effects of prostaglandin E2, propranolol and nitroglycerine with halothane, pethidine or pentobarbitone anaesthesia on arrhythmias and other responses to ligation of a coronary artery in rats.

The effects of various cardiovascular drugs (prostaglandin E2 (PGE2), propranolol and nitroglycerine) and anaesthetic regimens (halothane, pethidine and pentobarbitone), upon the outcome of coronary artery ligation in acutely prepared rats were determined. Effects upon arrhythmias, blood pressure, heart rate, mortality, ECG and the size of the occluded zone were determined for each drug in the presence of each anaesthetic. PGE2 and nitroglycerine had no statistically significant effects on the outcome of ligation whatever the anaesthetic. Propranolol had limited antiarrhythmic actions. The anaesthetic used had major effects upon the outcome of ligation, regardless of the cardiovascular drugs administered. Pentobarbitone anaesthesia resulted in the highest mortality, and most arrhythmias. Pethidine-N2O anaesthesia was associated with fewer arrhythmias. Halothane-N2O anaesthesia markedly decreased the incidence and severity of arrhythmias, independent of the cardiovascular drug. It was concluded that the anaesthetic used can have a major influence on ligation-induced arrhythmias in acutely prepared anaesthetized rats.

The effect of modification of sympathetic activity on responses to ligation of a coronary artery in the conscious rat.

1 Ligation of a coronary artery was performed in conscious rats whose sympathetic system activity had been altered by various treatments. 2 beta-Adrenoceptor blockade with acute (0.2 mg kg-1 plus 0.1 micrograms kg-1 min-1) or chronic (50-60 mg kg-1 daily for 12 days) propranolol treatment had little effect on arrhythmias, or other responses to ligation. 3 Abrupt withdrawal of chronic propranolol two days before ligation was also without effect. 4 Reduction of sympathetic activity acutely with labetalol (5 mg kg-1), or chronically with adrenomedullectomy and 6-hydroxydopamine treatment, accentuated the adverse effects of ligation. 5 The results of this study suggest that, while activity of the sympathetic system is not detrimental during ligation in the conscious rat, it may be important for survival.

A randomized phase III clinical trial of autologous blood stem cell transplantation comparing cryopreservation using dimethylsulfoxide vs dimethylsulfoxide with hydroxyethylstarch.

Hematopoietic stem cells intended for autologous transplantation are usually cryopreserved in solutions containing 10% dimethylsulfoxide (DMSO, v/v) or 5% DMSO in combination with 6% hydroxyethylstarch (HES, w/v). We performed a single-blinded, randomized study comparing these cryoprotectant solutions for patients undergoing autologous peripheral blood stem cell (PBSC) transplantation. A total of 294 patients were evaluable; 148 received cells frozen with 10% DMSO and 146 received cells frozen in 5% DMSO/6% HES. Patients who received cells frozen with the combination cryoprotectant recovered their white blood cell count >or=1.0 x 10(9)/l at a median of 10 days, one day faster than those who received PBSC frozen with DMSO alone (P=0.04). Time to achieve neutrophil counts of >or=0.5 x 10(9) and >or=1.0 x 10(9)/l were similarly faster for the recipients of the cells frozen in the combination solution. This effect was more pronounced for patients who received quantities of CD34+ cells higher than the median for the population. Median time to discontinuation of antibiotic use was also one day faster for the recipients of cells cryopreserved with DMSO/HES (P=0.04). In contrast, median times to recovery of platelet count >or=20 x 10(9)/l were equivalent for each group (10 days; P=0.99) and the median numbers of red cell and platelet transfusions did not differ.

Long-term cryopreservation of bone marrow for autologous transplantation.

Little is known about the effect of long-term cryopreservation on the viability of hematopoietic stem cells (HSC) or on the success of autologous bone marrow transplantation. Although progenitor cell assays such as culture of CFU-GM after thawing can be predictive of engraftment, the most rigorous assay for the cryosurvival of HSC is engraftment after reinfusion of stem cells. We retrospectively evaluated the engraftment data for 36 patients with hematologic malignancies or solid tumors treated at the Fred Hutchinson Cancer Research Center between 1981 and 1993 who received bone marrows stored for 2 years or more. The median duration of cryopreservation for this study group was 2.7 years (range 2.0-7.8). Ninety-seven percent of patients in the study group achieved a granulocyte count of > or = 0.5 x 1.0(9)/1 at a median of 19 days (range 10-115) vs 86% of control group (selected by diagnosis and date of storage) at a median of 20 days (P = 0.14). Seventy percent of patients in the study group achieved a platelet count > or = 20 x 10(9)/1 at a median of 27 days (range 9-69) vs 74% of control group at a median of 23 days (P = 0.47). Also, samples of 28 marrows cryopreserved for a median of 4.4 years (range 2.0-7.8) were cultured to determine if a loss of hematopoietic progenitors relative to duration of storage could be detected. The storage length was not predictive for the quantity of colonies formed (P = 0.57 for BFU-E-derived colonies; P = 0.65 for CFU-GM-derived colonies). We found no consistent detrimental effect of long-term cryopreservation on the success rate of autologous bone marrow transplantation. This report confirms previous reports that marrow cells cryopreserved for several years are capable of engrafting. Therefore, bone marrow cells may be stored at an early appropriate time before the side-effects of multiple cycles of chemotherapy and radiotherapy on hematopoietic tissues are incurred.

Isolation of CD34+ cells from blood stem cell components using the Baxter Isolex system.

The CD34 antigen is expressed by human hematopoietic progenitor and stem cells. These cells are capable of reconstituting marrow function after marrow-ablative chemo-radiotherapy. Several different technologies have been developed for the separation of CD34+ cells from bone marrow or peripheral blood stem cell (PBSC) components. We used an immunomagnetic separation technique to enrich CD34+ cells from PBSC components in anticipation of autologous transplantation for patients with B lymphoid malignancies. Twenty-nine patients enrolled on this study and received mobilization chemotherapy followed by G-CSF. Of these, 21 achieved a peripheral blood CD34+ cell level of at least 2.0 x 10(4)/l required by protocol for separation of the stem cell components. A median of three components per patient was collected for processing. The average CD34+ cell concentration in the components after apheresis was 1.0 +/- 1.2%. After the CD34+ cell selection, the enriched components contained 0.6 +/- 0.6% of the starting nucleated cells. The recovery of CD34+ cells, however, averaged 58.4 +/- 19.2% of the starting cell number, with a purity of 90.8 +/- 6.5%. Overall depletion of CD34- cells was 99.96 +/- 0.06%. Nineteen patients were treated with marrow-ablative conditioning regimens and received an average of 6.2 +/- 2.0 x 10(6) CD34+ cells/kg body weight. These patients recovered to an ANC >0.5 x 10(9)/l at a median of 11 days (range 8-14), and platelet transfusion independence at a median of 9 days (range 5-13). Four patients died of transplant-related complications or relapse before 100 days after transplantation. No patient required infusion of unseparated cells because of failure of sustained bone marrow function. These data demonstrate that peripheral blood-derived CD34+ cells enriched by use of an immunomagnetic separation technique are capable of rapid engraftment after autologous transplantation.

Quinacainol, a new antiarrhythmic with class I antiarrhythmic actions in the rat.

The antiarrhythmic and electrophysiological actions of quinacainol, a new Class I antiarrhythmic, were assessed in rats. Electrophysiological actions of quinacainol were assessed in vivo in terms of drug-induced changes in ECG, responses to left ventricular electrical stimulation, and changes in epicardial intracellular potentials to precisely characterize the electrophysiological effects of this putative subclass Ic antiarrhythmic compound. Antiarrhythmic actions were assessed in conscious rats subjected to occlusion of the LAD coronary artery. Antiarrhythmic actions occurred with 2.0 and 4.0 mg/kg, whereas 8.0 mg/kg was pro-arrhythmic. At doses of 0.5 mg/kg and above quinacainol increased threshold currents for capture and for ventricular fibrillation. Doses of 2.0 mg/kg and above increased ventricular refractoriness. From 1.0 to 8.0 mg/kg, quinacainol reduced dV/dtmax of phase 0 of epicardial action potentials but only 8.0 mg/kg increased action potential duration. The Q-T interval was also increased with the highest dose. Quinacainol dose-relatedly increased P-R interval whereas QRS did not change. Thus the Class I electrophysiological properties of quinacainol over the dose range tested did not fit accurately into a single subclass of the various subclasses of Class I. However, the Class Ic actions seen with 2.0 and 4.0 mg/kg were associated with antiarrhythmic actions.