ASA Group Research Articles

Patients' desire for information about anaesthesia: Danish attitudes.

Patients' desire for information about anaesthesia has been examined in a number of Commonwealth countries but not in Scandinavia. A questionnaire was distributed to form a basis for giving Danish patients more appropriate preoperative information. 201 preoperative patients in Denmark were asked to complete a questionnaire. The patients were divided into subgroups according to: age, gender, residential origin, ASA group, educational level, type of anaesthesia planned and number of previous anaesthetics. Patients from a city area required significantly more information than patients from a rural/urban area about premedication drugs, drips/catheters, pain/pain relief and complications. Men more than women preferred to know about dangerous complications. Information about pain/pain relief, duration of anaesthesia, and influence of anaesthesia on daily activities such as eating, drinking, mobilisation was given the highest priority, while unpleasant information such as about complications and needles was given the lowest priority. Meeting the anaesthetist and information about alternative methods of anaesthesia and premedication drugs were given only moderate priority. Ranking information in Denmark was significantly correlated with Scotland, Canada and Australia, despite profound differences in priority. More often than Danish patients, Australian patients felt they had right to know, and especially about complications. Patients from a city area required more information than patients from a rural/urban area. Information about the influence on daily activities was preferred to unpleasant information. Ranking information in Denmark was correlated with a number of Commonwealth countries.

The feasibility, safety and cost of infiltration anaesthesia for hernia repair

Data from 400 consecutive elective ambulatory operations for inguinal hernia under unmonitored local anaesthesia with limited pre-operative testing were prospectively obtained by the use of standardised files and questionnaires to assess the feasibility, patient satisfaction and potential cost reductions for such a technique. The median age of the patients was 59 years, and 29 operations were performed in ASA group III patients. The median postoperative hospital stay was 85 min. Conversion to general anaesthesia was necessary only in two cases, and nine patients needed overnight admission. One week postoperative morbidity was low with one case of transient cerebral ischaemia and one case of pneumonia, but no case of urinary retention. On follow-up, 88% were satisfied with the procedure, including unmonitored local anaesthesia. The cost reduction was at least £160 per patient compared with general/regional anaesthesia. We conclude that elective inguinal herniorrhaphy may be performed routinely under unmonitored local anaesthesia with a low postoperative morbidity, a high satisfaction rate and significant cost reductions.

Dose-dependent amplification by L-ascorbic acid of NaHCO3 promotion of rat urinary bladder carcinogenesis.

The dose dependence of L-ascorbic acid (AsA) copromotion of urinary bladder carcinogenesis with continuous concomitant administration of NaHCO3 was investigated. In the first experiment, 83 male F344 rats were all given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 wk and then divided into 5 groups, which received basal diet (Oriental MF) containing AsA at 0, 1, 2, 3.5, or 5% plus 1.5% NaHCO3 for 32 wk. Relative urinary bladder weights in the 5% AsA group were significantly increased as compared to the 0 or 1% group values due to the development of tumors. Both the incidence and number of microscopic urinary bladder lesions (tumors and preneoplastic lesions) showed dose-dependent increases. Furthermore, the sizes of the urinary bladder tumors (carcinomas and papillomas) were significantly increased with the highest dose, 5-bromo-2'-deoxyuridine labeling indices showed slightly increased proliferation in preneoplastic lesions of the urinary bladder epithelium with 5% AsA treatment. In a separate experiment, scanning electron microscopic observation revealed that administration of 5% AsA plus 1.5% NaHCO3 for 8 wk, without BBN, altered the urinary bladder surface. Elevation of urinary bladder epithelium AsA content, as well as urinary AsA, was also noted. Ornithine decarboxylase (ODC) activity and ODC messenger RNA levels in urinary bladder epithelium of rats treated with 1.5% NaHCO3 plus 5% AsA for 8 wk showed no statistically significant differences as compared to the control group. The results indicate that AsA amplifies the rat urinary bladder carcinogenesis promotion activity of NaHCO3 and that its intensity of action depends on the dose, particularly at high dose.

Intravenous regional anesthesia with 0.5% articaine, 0.5% lidocaine, or 0.5% prilocaine: A double-blind randomized clinical study

The purpose of this study was to compare the effectiveness of three local anesthetic agents for intravenous regional anesthesia in the upper limb. Side effects and plasma concentrations of the drugs in the doses administered for IVRA were also studied. Thirty patients in ASA groups I and II received intravenous regional anesthesia for surgery of the upper limb. In a double-blind prospective study, they were randomly allocated to receive one of three local anesthetics: articaine, lidocaine, or prilocaine. Patients received 40 mL of a 0.5% solution of the local anesthetic. The onset time of sensory block was assessed by pinprick and the extent of motor block was was scored as 0-3. Plasma concentrations of local anesthetics were determined in all patients from serial arterial blood samples drawn at predetermined times before and after tourniquet release. The onset time of sensory block was significantly shorter (2.5 minutes) in the articaine group than in the lidocaine group (11.1 minutes) or the prilocaine group (10.9 minutes) (Scheffe, P < .05). Development of motor block was equal in all three groups (score 2). Estimation of plasma concentrations by high performance liquid chromatography showed that the peak level in all 30 patients was reached immediately after release of the tourniquet; plasma concentrations thereafter gradually declined. Maximum concentrations of articaine, lidocaine, and prilocaine were, 1.85, 8.5, and 4.4 micrograms/mL, respectively. No signs of local anesthetic toxicity of the cardiovascular or central nervous systems were seen. Articaine had the fastest onset of sensory block and the lowest peak plasma concentration of the three local anesthetics when used for intravenous regional anesthesia.

Echocardiography values in the halothane uptake phase--measurement by acoustic quantification and manual evaluation

In 35 ASA group I and II patients we investigated the influence of haemodynamic changes induced by increasing concentrations of halothane (from 0.0 to 0.6% halothane in 70% N20) on parameters of transesophageal echocardiography (TEE). Measurements by TEE were taken in manual and automatic boundary detection mode. In manual mode the left ventricular endsystolic area (ESA) increased significantly (+16.3%) and the fractional area change (FAC) decreased significantly (-14.9%). There was no significant change of left ventricular end diastolic area (EDA). In the automatic mode there was a significant increase of ESA and EDA (+13.8%; +6.0%) and a significant decrease of FAC (-10.9%). Peak ejection rate (PER) and peak filling rate (PFR) which were also assessed in automated mode decreased significantly (-10.0%; -5.7%) under halothane. No change occurred with manually determined left ventricular endsystolic wall stress (LVEWS). The endsystolic quotient decreased significantly both in manual and automated mode during halothane (-28.3%; -29.9%). No significant difference existed between TEE measurements under apnoea versus under controlled ventilation (except for EDA in automated mode). We conclude that there is no need for apnoea conditions for TEE measurements. In conclusion, TEE proves a useful monitoring system in anesthesia which enables the investigator to assess the negative inotropic effect of halothane. Problems in its practical usage are due to the wide variation of TEE measurements.

Aspirin does not increase allogeneic blood transfusion in reoperative coronary artery surgery.

While preoperative aspirin (ASA) therapy does not increase allogeneic transfusion in elective primary coronary artery bypass grafting (CABG) operations, the impact of ASA consumption on transfusion in cardiac operations with greater risk of bleeding has not been investigated. We examined the influence of ASA consumption on mediastinal drainage and allogenic transfusion in 317 patients undergoing reoperative CABG surgery. Patients receiving ASA or ASA containing medications within 7 days preoperatively (n = 215) had similar perioperative characteristics but were older and had smaller red cell volumes than control patients not receiving ASA (n = 102). All patients received aminocaproic acid, but autotransfusion of mediastinal blood or platelet rich plasma, aprotinin, or desmopressin were not used. No significant differences were observed between ASA and control groups with respect to postoperative hematocrit, mediastinal drainage, frequency of reexploration for excessive bleeding, amount of allogeneic packed red blood cell, fresh frozen plasma, platelet concentrate or cryoprecipitate transfusion, or the fraction of patients receiving any allogeneic blood product. There was no difference in mediastinal drainage when stratified by timing of most recent ASA ingestion. Multiple linear regression identified duration of cardiopulmonary bypass (CPB), internal mammary artery harvesting, chronic preoperative steroid therapy and use of an intraaortic balloon pump (IABP) as significant predictors of mediastinal drainage. Logistic regression demonstrated that female gender, prolonged duration of CPB, advanced age, use of IABP, and a negative history of smoking were significant independent predictors of blood product transfusion. There was no significant interaction of preoperative heparin therapy with ASA on transfusion demonstrated by univariate or multivariate analyses. These results indicate that preoperative ASA ingestion is not an important determinant of mediastinal drainage or allogeneic transfusion, even after repeat CABG operations, and that surgical and patient characteristics are more important predictors of these outcomes.

Aspirin Does Not Increase Allogeneic Blood Transfusion in Reoperative Coronary Artery Surgery

While preoperative aspirin (ASA) therapy does not increase allogeneic transfusion in elective primary coronary artery bypass grafting (CABG) operations, the impact of ASA consumption on transfusion in cardiac operations with greater risk of bleeding has not been investigated.We examined the influence of ASA consumption on mediastinal drainage and allogeneic transfusion in 317 patients undergoing reoperative CABG surgery. Patients receiving ASA or ASA containing medications within 7 days preoperatively (n = 215) had similar perioperative characteristics but were older and had smaller red cell volumes than control patients not receiving ASA (n = 102). All patients received aminocaproic acid, but autotransfusion of mediastinal blood or platelet rich plasma, aprotinin, or desmopressin were not used. No significant differences were observed between ASA and control groups with respect to postoperative hematocrit, mediastinal drainage, frequency of reexploration for excessive bleeding, amount of allogeneic packed red blood cell, fresh frozen plasma, platelet concentrate or cryoprecipitate transfusion, or the fraction of patients receiving any allogeneic blood product. There was no difference in mediastinal drainage when stratified by timing of most recent ASA ingestion. Multiple linear regression identified duration of cardiopulmonary bypass (CPB), internal mammary artery harvesting, chronic preoperative steroid therapy and use of an intraaortic balloon pump (IABP) as significant predictors of mediastinal drainage. Logistic regression demonstrated that female gender, prolonged duration of CPB, advanced age, use of IABP, and a negative history of smoking were significant independent predictors of blood product transfusion. There was no significant interaction of preoperative heparin therapy with ASA on transfusion demonstrated by univariate or multivariate analyses. These results indicate that preoperative ASA ingestion is not an important determinant of mediastinal drainage or allogeneic transfusion, even after repeat CABG operations, and that surgical and patient characteristics are more important predictors of these outcomes. (Anesth Analg 1996;83:1178-84)

Aspirin versus Indomethacin Treatment of Patent Ductus Arteriosus in Preterm Infants with Respiratory Distress Syndrome

Indomethacin (Indo) is commonly used for treatment of patent ductus arteriosus (PDA) but has renal failure as a main side effect. Aspirin (ASA) is an alternative, but there are no controlled trials on its efficacy. We randomly assigned 75 premature infants suffering from respiratory distress syndrome (RDS) (mean gestational age: 29.6 +/- 2.5 wk, mean birth weight: 1295 +/- 464 g) (+/- SD) and on artificial ventilation at the start of the study (mean: 3.4 d of life), to either Indo (3 x 0.2 mg/kg/12 h) or ASA (4 x 15 mg/kg/6 h). PDA and degree of shunting were evaluated by echocardio-Doppler; side effects were carefully recorded. PDA closed in 35/38 patients from the Indo group (92%) and in 16/37 patients from the ASA group (43%) (p < 0.0001). Nineteen patients needed further treatment with Indo or surgery (17 in the ASA group and 2 in the Indo group). The only side effect observed was a decrease of uresis in the Indo group during 4 d post treatment (p < 0.01). Closing of PDA was positively correlated with gestational age, but not with time of starting Indo/ASA or grade of shunting. We conclude that ASA is not as effective in closing PDA as Indo, but has no adverse effect on uresis.

Effects of lovastatin in prevention of restenosis after percutaneous transluminal angioplasty in lower limbs

Percutaneous transluminal angioplasty (PTA) is frequently complicated by restenosis of the dilated arterial segment within a few months after the angioplasty. Cholesterol-lowering drugs have been shown to reduce the rate of restenosis after PTA, but the role of lipid fractions in susceptibility to restenosis after balloon angioplasty is not clear. The present prospective and randomized study was executed to find out the effects of lovastatin on restenosis after PTA in the arteries below the inguinal ligament. PTA was performed in 37 patients (age 68 ± 12 years) because of severe claudication or critical ischemia of lower limbs. Regardless of their preoperative blood cholesterol level, all patients were given diet information and thereafter randomized into two groups, one receiving 250 mg asetosalisylic acid (ASA group, n = 19) and one receiving 250 mg ASA and 20 mg of lovastatin (lovastatin group, n = 18) daily. Clinical status was followed up for 1, 4, and 12 months after PTA. Control angiography was performed in every patient 12 months after PTA. However, if the clinical status suggested critical ischemia, angiography and necessary procedures were performed before 12 months. Two radiologists evaluated all angiographs independently and without knowledge of the medication patients were receiving. In the ASA group, forty-two percent (8/19) of the patients had total restenosis of the dilated segment 4.5 ± 1.2 months after the first PTA, whereas only 22.2% (4/18) of the patients in the lovastatin group had total restenosis 2.8 ± 1.5 months after the initial treatment. There were 2/18 amputations (11.1%) in the lovastatin group and 4/19 (21.1%) in the ASA group during the first year of surveillance. Total plasma cholesterol decreased from 6.0 ± 1.1 mmol/L to 5.0 ± 1.4 mmol/L, and cholesterol index (total cholesterol/ HDL-cholesterol) decreased from 5.4 ± 2.3 to 4.9 ± 2.5 in the lovastatin group during the follow-up period. In the ASA group, both plasma total cholesterol and cholesterol index stayed virtually at the same level. The number of restenosis and amputations in the ASA group was twice as high as in the lovastatin group 1 year after PTA. These preliminary results suggest that lovastatin has a beneficial effect on restenosis after balloon angioplasty.

Aspirin Does Not Increase Homologous Blood Requirements in Elective Coronary Bypass Surgery

Studies have demonstrated increased homologous blood product requirements in patients on aspirin (ASA) undergoing cardiac surgery. We reexamined the influence of ASA therapy on hemorrhage and transfusion requirements in patients undergoing elective coronary artery bypass (CAB) surgery in light of recent transfusion-sparing practices and autologous cell salvaging techniques. Records from 197 patients who underwent reinfusion of postoperatively shed mediastinal autologous whole blood were retrospectively reviewed, including 87 patients who received ASA within 1 wk prior to surgery and 110 control patients. Patients undergoing repeat cardiac operations were excluded from the study. Cardiopulmonary bypass (CPB) duration, procedure length, aortic cross-clamp time, and number of grafts performed did not differ significantly between groups. None of the patients required reexploration for bleeding. There was significantly more mediastinal tube drainage in the ASA group (27%), but it did not affect homologous blood component requirements because this blood was autotransfused. In addition, there were no significant differences in platelet, fresh frozen plasma, and cryoprecipitate use between the groups. Thus, ASA did increase bleeding but did not increase homologous blood transfusion requirements in elective CAB surgery.

ASPIRIN VERSUS INDOMETHACINE TREATMENT OF PATENT DUCTUS ARTERIOSUS (PDA) IN THE PRETERM NEONATE WITH RESPIRATORY DISTRESS SYNDROME (RDS)

Indomethacine (Indo) is commonly used for treatment of PDA, its main side effect is renal failure. Aspirin (ASA) is an alternative but there are no controlled trials on its efficacy. We randomly assigned 75 premature infants suffering from RDS (mean GA: 29.6 ± 2.5 wks, mean BW: 1295 ± 464 gr) on artificial ventilation at start of study (mean : 3.4 day of life), to either Indo (3 × 0.2 mg/kg/12 hrs) or ASA (4 × 15 mg/kg/6 hrs). PDA and degree of shunting were diagnosed by echocardio-Doppler at start and after 2 and 4 days. Side effects, especially diminution of diuresis, were carefully recorded. Results: PDA closed in 35/38 patients from the Indo group (93 %) and in 16/37 patients from the ASA group (43 %) (p<0.001). No reopenings were observed in both groups. 19 patients needed further treatment with Indo or surgery (17 in the ASA group and 2 in the Indo group). No side effects ware seen in both groups except for a decrease of diuresis in the Indogroup during 4 posttreatment days (difference on 2nd posttreatment day: Indo minus 1.06 ml/kg/h vs ASA: plus 0.48 ml/kg/h; p<0.01). Fluid management was not different between both groups. Closing of PDA was positively correlated with CA, but not with time of starting Indo/ASA or grade of shunting. Conciusion:ASA is not as effective in closing PDA as Indo, but has no adverse effect on diuresis.

Patient evaluation of four different combinations of intravenous anaesthetics for short outpatient procedures

We studied 200 female patients (ASA group 1) scheduled for termination of pregnancy under general anaesthesia. The patients were randomly allocated to receive one of four anaesthetic combinations; (1) propofol in combination with ketamine 20 mg, (2) propofol in combination with fentanyl 0.1 mg, (3) thiopentone in combination with fentanyl 0.1 mg, (4) methohexitone in combination with fentanyl 0.1 mg. All patients were breathing oxygen in nitrous oxide 1:2. Patients' self assessments of per- and postoperative course and time to discharge were compared. No patient's response suggested light anaesthesia, but dreams were frequently experienced during anaesthesia especially among the propofol-ketamine combination (29 out of 50). Time to discharge was shortest for the groups of patients given propofol; the mean time was 93 and 96 min for the ketamine and fentanyl groups respectively. During the recovery period significantly more patients experienced pain in the ketamine-propofol group. Complaints of nausea were seen in only 15 patients, and seven patients noted psycho-mimetic side effects during recovery, without any differences between the groups. All four combinations tested offered good conditions for short outpatient procedures. However, the propofol-fentanyl combination was found to offer the best quality of anaesthesia as assessed by the patients themselves.

DOSE-RESPONSE RELATIONSHIPS FOR EDROPHONIUM AND NEOSTIGMINE ANTAGONISM OF MIVACURIUM-INDUCED NEUROMUSCULAR BLOCK

We have studied the dose-response relationships for neostigmine and edrophonium during antagonism of neuromuscular block induced by mivacurium chloride. Sixty-four ASA group I or II adults were given mivacurium 0.15 mg kg-1 during fentanyl-thiopentone-nitrous oxide-isoflurane anaesthesia. Train-of-four stimulation (TOF) was applied to the ulnar nerve every 10 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height reached 10% of its initial control value, edrophonium 0.1, 0.2, 0.4, or 1 mg kg-1 or neostigmine 0.005, 0.01, 0.02, or 0.05 mg kg-1 was administered by random allocation. Neuromuscular function in another 16 subjects was allowed to recover spontaneously. Spontaneous recovery from 90% mivacurium block to 95% twitch height and TOF ratio 0.75 occurred within 15 min. This study demonstrated that the dose-response curves for these two drugs for antagonism of neuromuscular block (first twitch and train-of-four ratio) were parallel. The doses of neostigmine required to achieve 50% (ED50) and 70% (ED70) recovery of the first twitch after 10 min were 2 (1.5-2.5) micrograms kg-1 and 4.7 (4.1-5.4) micrograms kg-1 (mean (95% confidence intervals)), respectively. Corresponding ED50 and ED70 values for edrophonium were 2.8 (0.75-10.2) micrograms kg-1 and 9.2 (3.6-23.6) micrograms kg-1, respectively. These values corresponded to neostigmine:edrophonium potency ratios of 1.4 (0.4-2.4) and 1.95 (0.9-2.9) for first twitch ED50 and ED70 height, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Problems with Regional Anaesthesia: An Analysis of 2000 Incident Reports

There were 160 incidents associated with regional anaesthesia amongst the first 2000 incidents reported to the Australian Incident Monitoring Study. They were categorised into 6 groups; epidural anaesthesia (83), spinal anaesthesia (42), brachial plexus blocks (14), intravenous local anaesthesia (4), ocular blocks (3), and local infiltration (14). The largest single cause of incidents involved circulatory problems; these occurred in all the groups except brachial plexus block (30 cases of hypotension, 7 of arrhythmias, 3 of cardiac arrest, 2 of hypertension and 1 of myocardial ischaemia). There were 24 drug errors, of which 10 involved the "wrong drug" and 4 "inappropriate use". With the exception of these, all the remainder involved problems specific to regional anaesthesia: 26 inadvertent dural punctures; 19 failed or inadequate blocks; 14 dural puncture headaches (all cured by blood patches); 10 inadvertent total or high spinal blocks (of which 7 required artificial ventilation); 5 blocks on the wrong side or in the wrong patient; 3 late hypoxic incidents and a variety of miscellaneous problems. Three-quarters of all incidents occurred in the presence of an anaesthetist and over 90% in patients of ASA Groups I-III. Rapid recognition by the anaesthetist prevented many potentially life threatening events, and the only death was as a result of surgical bleeding.

ISOBOLOGRAPHIC AND DOSE-RESPONSE ANALYSIS OF THE INTERACTION BETWEEN PIPECURONIUM AND VECURONIUM

We have studied the neuromuscular effects of pipecuronium, vecuronium and their combination in 130 ASA group I or II patients. Patients were anaesthetized with 0.8% halothane and 60% nitrous oxide in oxygen. Neuromuscular block was recorded as the evoked thenar mechanomyographic response to train-of-four stimulation of the ulnar nerve (2 Hz at 10-s intervals). The dose-response curves were determined by probit analysis. The calculated doses producing 50% depression of the first twitch height were 15.6, 16.9 and 15.0 micrograms kg-1 for the pipecuronium, vecuronium and pipecuronium-vecuronium combination groups, respectively. Isobolographic and algebraic (fractional) analyses were used to assess quantitatively the combined neuromuscular effect of pipecuronium and vecuronium and to define the type of interaction between these drugs. The interaction between pipecuronium and vecuronium was found to be additive.

INDUCTION DOSE-RESPONSE STUDIES WITH PROPOFOL AND THIOPENTONE

The relative potencies of propofol and thiopentone were assessed using different indicators of induction of anaesthesia: abolition of the response to verbal commands and eyelash stimulation. Log-probit dose-response curves for these end-points were determined 30, 60 and 90 s after induction in 96 unpremedicated ASA group I patients. For propofol, ED50 values for abolition of the response to verbal commands and eyelash stimulation at different time intervals were in the ranges 1.16-1.42 and 1.23-1.72 mg kg-1, respectively; corresponding ED95 values were 2.18-2.67 and 2.42-3.27 mg kg-1, respectively. For thiopentone, the calculated ED50 values for verbal commands and eyelash stimulation at the same time intervals were 1.81-2.23 and 3.55-3.40 mg kg-1; corresponding ED95 values were 5.11-6.29 and 6.41-6.70 mg kg-1, respectively. The potency ratio of propofol to thiopentone observed in this study varied from 1:1.27 to 1:2.88. It is concluded that a dose-response curve reflecting one end-point of anaesthesia cannot be used to define another end-point of anaesthesia.

Effect of Intravenous γ‐Globulin on Neutrophil Function in Kawasaki Disease

The effect of intravenous gamma-globulin (IVGG) on the neutrophil count and neutrophil chemiluminescence (CL) of patients with Kawasaki Disease (KD) was investigated. Forty patients with KD were enrolled in the study. Ten patients were treated with 100 mg/kg/day of gamma-globulin for five days (GG 100 group) and 14 patients were treated with 400 mg/kg/day of gamma-globulin (GG 400 group) for five days. These patients also took aspirin. Sixteen patients were treated with aspirin alone (ASA group). The neutrophil counts were significantly lower in the GG 400 and GG 100 groups than in the ASA group, three days, and one and two weeks after the start of treatment. Neutrophil CL of the GG 400 and GG 100 groups was significantly lower than in the ASA group one and two weeks after the start of treatment. In the in vitro study, gamma-globulin had a dose-dependent suppressive effect on the neutrophil CL in the early stage. Albumin had similar effects. The suppressive effect of gamma-globulin on CL was not specific. These findings suggest that IVGG is effective in reducing the production of active oxygen which is considered responsible for the vascular damage in the early stage of KD.

A randomized prospective assessment of recombinant leukocyte A human interferon with or without aspirin in advanced renal adenocarcinoma.

We performed a prospective, controlled trial of recombinant leukocyte A interferon (IFN-alpha 2A) with or without aspirin (ASA) in 176 patients with assessable advanced renal cell cancer in light of a 34% response rate (10 of 29 patients) from the two-agent regimen in an earlier nonrandomized trial. This encouraging result was substantially higher than the 15% response rate typically achieved with IFN therapy alone. Eighty-seven patients received IFN-alpha 2A 20 x 10(6) U/m2 intramuscularly three times a week, and 89 received the same IFN therapy with ASA 600 mg orally four times each day. Each group was balanced as to relevant prognostic discriminants. Response rates were 8% for the group receiving ASA in addition to IFN, and 13% for the group receiving IFN alone (P = .30). The median times to progression were 1.9 months for the group receiving IFN with ASA and 2.7 months for the group receiving IFN alone (log-rank P = .36). The median survival durations were 8.8 months for the IFN and ASA group and 8.0 months for the IFN-only group (log-rank P = .60). These figures are also inferior to those typically reported from other studies. Our findings reemphasize the crucial role of randomized trials, admittedly cumbersome and time-consuming, to determine accurately the value of apparently promising therapies. Although some patients may derive benefit from IFN therapy, our findings raise disturbing questions regarding the potential IFN-alpha 2A according to the dose and schedule used in this trial to have any substantive impact on the ultimate outcome of disseminated renal cell cancer.

Intravenous γ‐Globulin for Kawasaki Disease

We studied the effect of gamma-globulin (IVGG) and aspirin (ASA) on the development of the coronary artery lesions (CAL) of Kawasaki disease (KD) in three different protocols. Within 29 days of the onset of KD the echocardiographic evidence of CAL had developed in 39-42% of the patients in the ASA group, but only in 13.7-20.8% of the patients treated with IVGG (200 or 400 mg/kg X 5). In long-term follow-up observation of CAL of these patients the evidence of CAL in both the ASA and the IVGG group regressed gradually; however, the residual rate of CAL was significantly low in the IVGG group at all times up to 24 months after onset. These facts suggest that when using IVGG for KD, we should select a dose of intact gamma-globulin, 1,000 mg/kg or more in total, to prevent the occurrence of CAL. We have demonstrated not only a significant reduction in the occurrence of CAL in patients treated with IVGG but a reduction in the residual rate of CAL for two years as compared with those treated by ASA.

Effect of Low-Dose Aspirin on Platelet Adherence After Carotid Endarterectomy in Dogs

The study was undertaken to determine the influence of various doses of aspi rin (ASA) therapy on platelet adherence to injured endothelium. Twenty-four mongrel dogs were assigned to one of four treatment groups in a randomized, blinded fashion. Each group received ASA in one of three doses: 1 mg/kg, 5 mg/kg, or 10 mg/kg or no ASA therapy (control group). After five days of ASA therapy, the dogs underwent unilateral carotid endarterectomy (CEA), in a ran domized fashion, with the contralateral carotid artery serving as control within each dog. Indium 111 oxine-labeled autologous platelets were injected into the dogs twenty minutes before the reestablishment of flow through the endarterec tomized carotid artery. Platelet scintigraphy was performed at hours 3, 24, 48 and 72 postoperatively. ASA therapy was continued postoperatively for seventy- two hours. Data were analyzed by comparing the mean platelet uptake ratios (operative to nonoperative sites) between groups. When all ASA groups were combined and compared with control values, ASA therapy significantly decreased (p &lt; 0.05) platelet adherence up to seventy-two hours postoperatively. The same effect was observed with low- (1 mg/kg) and medium- (5 mg/kg) dose ASA, which significantly reduced (p &lt; 0.05) platelet adherence to the endarterectomized site at hours 3, 24, 48, and 72. In contrast, there was no significant reduction in platelet uptake in the high-dose (10 mg/kg) ASA group. These results indi cate that ASA therapy given in a dosage of 1 or 5 mg/kg for at least five days preoperatively is beneficial in decreasing platelet adherence after CEA in dogs. Conversely, at a dose of 10 mg/kg, platelet uptake is not consistently inhibited. This study supports previous findings that lower doses of ASA (1-5 mg/kg) are superior to high-dose ASA (10 mg/kg) in inhibiting platelet adherence to injured endothelium in vivo.