Marking hypoxia in rat prostate carcinomas with beta-D-[125I]azomycin galactopyranoside and.

UNLABELLED: The purpose of this study was to determine, with a rodent tumor model, if microelectrode measurements of unmodulated tumor oxygenation predict for the avidity of hypoxic markers to tumor tissue. METHODS: The rapidly growing, anaplastic variant of the Dunning rat prostate carcinoma cell line (R3327-AT) was implanted subcutaneously on the upper backs of Fischer X Copenhagen rats. Approximately 100 measurements of PO2 were obtained from tumors of 5-10 g in animals that were restrained and then subjected to different anesthetic procedures. Values of median PO2 (in mm Hg) and percentage of measurements <5 mm Hg obtained from individual tumors were used to define tumor oxygenation status. The radiodiagnostic hypoxic markers beta-D-iodinated azomycin galactopyranoside (IAZGP) and [99mTc]HL-91 were simultaneously administered to 26 animals whose tumor oxygen levels had been measured. Six hours after marker administration, the animals were killed; tumor, blood, and muscle tissues were sampled; and percentage injected dose per gram (%ID/g*), tumor/blood ratio (T/B), and tumor/muscle ratio (T/M) parameters were determined. Parameters of marker avidity to individual tumors were linearly correlated with microelectrode measurements of tumor oxygenation to determine the significance of inverse associations. RESULTS: The median PO2 of 41 tumors varied from 2.0 to 20.9 mm Hg, with an average value of 7.5 +/- 1.4 mm Hg. Six tumors had unusually high values; that is, >10 mm Hg, and when these were excluded from the analysis, the average median PO2 of the remaining 35 was 4.3 +/- 0.7 mm Hg. When electrode measurements of tumor oxygenation were obtained under conditions of halothane anesthesia with the animals breathing O2, carbogen, or air, median PO2 values increased significantly (P = 0.001). When animals were deeply anesthetized by intraperitoneal injection of ketamine-xylazine, median PO2 values were not significantly different (P = 0.13) from those obtained while the animals were restrained and breathing air. There was no inverse correlation of significance between the electrode measurements of median PO2 and the avidity of beta-D-IAZGP nor [99mTc]HL-91 in this tumor model. The range of median PO2 values in these tumors was at least 3 mm Hg, and the range of hypoxic marker avidity was less than twofold. CONCLUSION: These data demonstrate that microelectrode measurements of rat tumor oxygenation did not correlate with the avidity of the two hypoxic markers, at least in this tumor model. The larger dynamic range of tumor oxygen measurements obtained with microelectrodes might be biased to low values by their necrotic fractions, the zones within solid tumors that contain dead cells and debris that will not be labeled by bioreducible hypoxic markers. Hypoxic marker avidity to individual tumors will have to be validated by other assays that can predict for their radiosensitivity.

Single-photon emission computed tomography and positron-emission tomography assays for tissue oxygenation.

Radiotherapy prescription can now be customized to target the major mechanism(s) of resistance of individual tumors. In that regard, functional imaging techniques should be exploited to identify the dominant mechanism(s). Tumor biology research has identified several mechanisms of tumor resistance that may be unique to radiation treatments. These fall into 3 broad areas associated with (1) tumor hypoxic fraction, (2) tumor growth rate, (3) and the intrinsic radiosensitivity of tumor clonogens. Imaging research has markers in various stages of development for quantifying relevant information about each of these mechanisms, and those that measure tumor oxygenation and predict for radioresistance are the most advanced. Positron-emission tomography (PET) measurement of oxygen 15 has yielded important information, particularly about brain tissue perfusion, metabolism, and function. Indirect markers of tumor hypoxia have exploited the covalent binding of bioreductive intermediates of azomycin-containing compounds whose uptakes are inversely proportional to intracellular oxygen concentrations. Pilot clinical studies with single-photon emission computed tomography (SPECT) and PET detection of radiolabeled markers to tumor hypoxia have been reported. Recently, other studies have attempted to exploit the reduction properties of both technetium and copper chelates for the selective deposition of radioactive metals in hypoxic tissues. A growing number of potentially useful isotopes are now available for labeling several novel chemicals that could have the appropriate specificity and sensitivity. Preclinical studies with "microSPECT" and "microPET" will be important to define the optimal radiodiagnostic(s) for measuring tissue oxygenation and for determining the time after their administration for optimal hypoxic signal acquisition. Radiolabeled markers of growth kinetics and intrinsic radiosensitivity of cells in solid tumors are also being developed. We conclude that radiation oncology is uniquely positioned to benefit from functional imaging markers that identify important mechanisms of tumor radioresistance, since several strategies for overcoming these individual mechanisms have already been identified.

Assessment of perfusion toward the aortic valve using the new dispersion aortic cannula during coronary artery bypass surgery.

When there is an echocardiographic diagnosis of severe mobile atherosclerotic plaque in the aortic arch or descending aorta, perfusion toward the aortic arch during cardiopulmonary bypass may create a high risk of embolic neurologic injury. Other perfusion methods, such as cannulation of the femoral or axillary arteries, are not always possible, due to atherosclerosis. The ascending aorta may be an alternative site for perfusion, since it is less frequently diseased. We assessed a new technique of perfusion toward the aortic valve using a new cannula designed for this purpose (Dispersion aortic cannula). Our study included 100 consecutive patients, 72 men and 28 women, with an average age of 68 +/- 1.0 years (range, 39-89 years). There were no complications related to insertion of the cannula or perfusion. The ascending aorta could be cross-clamped and side-clamped without perfusion problems. Three deaths occurred; none was related to the cannulation technique. No intra-operative stroke occurred. Two patients suffered neurologic events, one on day 1 and the other on day 6; both had been fully alert after surgery. Perfusion toward the aortic valve appears to be safe and hemodynamically effective. This cannulation technique appears to be an acceptable alternative to present methods. Comparative studies will be needed to determine whether this alternative technique is effective in patients with severe aortic arch disease.

Pneumococcal infections in HIV-infected adults.

Bacterial pneumonia, specifically pneumococcal infection, is a frequent cause of morbidity and mortality in persons infected with human immunodeficiency virus (HIV). It causes morbidity directly and possibly progression of HIV infection. The clinical presentation and response to therapy are usually similar to that of patients without HIV infection, although radiographic presentations may be atypical. There is a higher incidence of invasive disease and extrapulmonary disease, and mortality may be increased in HIV-infected patients. HIV infection impairs the host response to pneumococcus in a variety of ways. Colonization with Streptococcus pneumoniae may be prolonged for reasons that are incompletely understood. Concern about the rising prevalence of resistant pneumococcal strains is increasing, but the clinical relevance is uncertain. At least 90% of the strains that cause invasive disease are present in the 23-valent pneumococcal vaccine. The response to vaccination declines as immunodeficiency progresses; however, the potential benefit to responders is great and the risk is minimal. Therefore, this vaccine is recommended for all HIV-infected persons.

Screening and noninvasive testing for pulmonary disease.

Although detection of preclinical disease using screening tests is desirable if earlier treatment improves outcome, the available data show no morbidity or mortality benefit using chest radiography, sputum analysis for Pneumocystis carinii and acid-fast bacilli, or serial measurements of single-breath carbon monoxide diffusing capacity to detect pulmonary disease in asymptomatic persons with HIV. It seems prudent to evaluate asymptomatic patients periodically with a careful history and focused physical examination and to perform only those tests that are likely to alter the plan of management such as tuberculin skin testing, CD4 lymphocyte measurement, and measurement of viral burden. Noninvasive diagnostic studies including chest radiography, arterial blood gas analysis, induced or expectorated sputum analysis, exercise testing, and nuclear scans should be performed if new pulmonary symptoms are observed. The use of these tests should be guided by the clinical presentation and followed, when necessary, by the appropriate invasive studies.

Bacterial pneumonia.

Bacterial pneumonia is significantly more common in persons who are HIV-infected than in the general population and is most common among injection drug users and in persons with advanced HIV disease and immunosuppression. The clinical features of bacterial pneumonia are similar to those in HIV-seronegative persons, but bacteremia is more common. When a pathogen is identified, Streptococcus pneumoniae is consistently the most common, occurring in 20% to 70% of cases. Haemophilus influenzae, Staphylococcus aureus, Escherichia coli, and other gram-negative organisms are mainly responsible for the remainder of bacterial pneumonia episodes in the United States, Central Africa, Australia, and England. In some studies, Chlamydia pneumoniae was recognized as a common cause in persons with early HIV disease, whereas Pseudomonas aeruginosa is recognized as a community- and hospital-acquired lower respiratory tract pathogen in patients with severe immunosuppression. Although antimicrobial therapy is frequently empiric, it should be tailored to the severity of illness, local prevalence of infections, resistance patterns, or when an etiologic agent is identified. The treatment response is similar in patients with and without HIV infection, but bacterial pneumonia may accelerate the progression of HIV disease. Preventative measures include use of the polyvalent pneumococcal vaccine, especially early in the course of HIV infection, when it is most likely to be effective. The incidence of bacterial pneumonia is also reduced in HIV-seropositive persons who use trimethoprim-sulfamethoxazole to prevent Pneumocystis carinii pneumonia.

Preclinical assessment of hypoxic marker specificity and sensitivity.

PURPOSE: In the search for a sensitive, accurate, and noninvasive technique for quantifying human tumor hypoxia, our laboratory has synthesized several potential radiodiagnostic agents. The purpose of this study was to assess and compare the hypoxic marking properties of both radioiodinated and Tc-99m labeled markers in appropriate test systems which can predict for in vivo activity. MATERIALS AND METHODS: Preclinical assessment of hypoxic marker specificity and sensitivity employed three laboratory assays with tumor cells in vitro and in vivo. Radiolabeled marker uptake and/or binding to whole EMT-6 tumor cells under extremely hypoxic and aerobic conditions was measured and their ratio defined hypoxia-specific factor (HSF). Marker specificity to hypoxic tumor tissue was estimated from its selective avidity to two rodent tumors in vivo, whose radiobiologic hypoxic fractions (HF) had been measured. The ratios of % injected dose/gram (%ID/g) of marker at various times in EMT-6 tumor tissue relative to that in the blood and muscle of scid mice were used to quantify hypoxia-specific activity. This tumor in this host exhibited an average radiobiologic HF of approximately 35%. As well, nuclear medicine images were acquired from R3327-AT (HF approximately =15%) and R3327-H (no measurable HF) prostate carcinomas growing in rats to distinguish between marker avidity due to hypoxia versus perfusion. RESULTS: The HSF for FC-103 and other iodinated markers were higher (5-40) than those for FC-306 and other Tc-99m labeled markers. The latter did not show hypoxia-specific uptake into cells in vitro. Qualitative differences were observed in the biodistribution and clearance kinetics of the iodinated azomycin nucleosides relative to the technetium chelates. The largest tumor/blood (T/B) and tumor/muscle (T/M) ratios were observed for compounds of the azomycin nucleoside class in EMT-6 tumor-bearing scid mice. These markers also showed a 3-4 x higher uptake into R3327-AT tumors relative to the well-perfused R3327-H tumors. While both FC-306 and CERETEC rapidly distributed at unique concentrations to different tissues, their avidity to EMT-6 and R3327-AT tumors did not correlate with tumor HF. CONCLUSIONS: The halogenated azomycin nucleosides with the lowest lipid/water partition coefficient values were found to yield the optimal hypoxia-specific signal in these animal tumors. Our Tc-99m-labeled azomycin chelates showed little or no hypoxia-specific uptake and had in vivo biodistribution and clearance kinetics similar to those of CERETEC, a perfusion agent with no known hypoxic binding activity.

A dual hypoxic marker technique for measuring oxygenation change within individual tumors.

Rodent tumour models have been the 'workhorse' for tumour oxygenation research and for investigating radiobiological hypoxic fraction. Because of the intertumour heterogeneity of blood flow and related parameters, most studies have pooled information derived from several different tumours to establish the statistical significance of specific measurements. But it is the oxygenation status of and its modulation in individual tumours that has important prognostic significance. In that regard, the bioreducible hypoxic marker technique was tested for its potential to quantify oxygenation changes within individual tumours. Beta-D-iodinated azomycin galactoside (IAZG) and beta-D-iodinated azomycin xylopyranoside (IAZXP) were each radiolabelled with Iodine-125 and iodine-131 for measurements of animal tumour oxygenation. The tumour-blood (T/B) ratio of marker radioactivity in mice after the renal excretion of unbound marker (at 3 h and longer times) had been shown to be proportional to radiobiological hypoxic fraction. When markers labelled with both radioisotopes were administered simultaneously to EMT-6 tumour-bearing scid mice, T/B ratios were found to vary by up to 300% between different tumours, with an average intratumour variation of only approximately 4%. When the markers were administered 2.5-3.0 h apart, changes in T/B ratios of 8-25% were observed in 10 out of 28 (36%) tumours. Changes to both higher and lower hypoxic fraction were observed, suggestive of acute or cycling hypoxia. When 0.8 mg g(-1) nicotinamide plus carbogen was administered to increase tumour oxygenation, reductions in T/B ratios (mean deltaT/B approximately 38%) were observed in all tumours. Similar results were obtained with Dunning rat prostate carcinomas growing in Fischer x Copenhagen rats whose T/B ratios of IAZG and radiobiological hypoxic fractions are significantly lower. These studies suggest that fluctuating hypoxia can account for at least 25% of the total hypoxic fraction in some tumours and that correlations between bioreducible marker avidity and related tumour properties will be optimal when the independent assays are performed over the same time period. This dual hypoxic marker technique should prove useful for investigating both spontaneous and induced oxygenation changes within individual rodent tumours.

Measuring hypoxia and predicting tumor radioresistance with nuclear medicine assays.

Tumor cells at low oxygen tension are relatively radioresistant. The hypoxic fraction of individual tumors before, during and after radiotherapy is likely to have prognostic value but its diagnosis still awaits an accurate and acceptable assay. The recent indications that hypoxia can also induce the expression of specific genes and promote a more aggressive tumor phenotype makes its diagnosis even more important. Over 15 years ago, misonidazole, an azomycin-based hypoxic cell radiosensitizer, was found to link covalently to cellular molecules at rates inversely proportional to intracellular oxygen concentration. The use of bioreducible markers to positively label zones of viable hypoxic cells within solid tumors and to predict for tumor radioresistance was proposed. Several hypoxic markers have now been identified and their selective binding within tumors has been measured by both invasive and non-invasive assays. Research from our laboratory has emphasized both mechanistic and preclinical studies associated with nuclear medicine procedures for measuring tumor hypoxia and predicting tumor radioresistance. This report updates radiation oncologists about the status of nuclear medicine hypoxic marker research and development as of mid-1997. While several potential imaging agents have been identified, their testing and validation in appropriate human tumors will require focused research efforts by individual academic departments and, possibly, by clinical trials performed through cooperative groups. Since the prediction of hypoxia in individual tumors could strongly impact radiotherapy treatment planning, the radiation oncology research community is best positioned to execute the validation studies associated with these markers.

Pulmonary complications of HIV infection.

With changes in epidemiology and the application of newer treatment and prophylactic regimens, the types of pulmonary diseases that occur in HIV-infected persons are changing. New ways to assess the progression of HIV disease and new antiretroviral treatments are available. Increased survival is often coupled with worsening immunosuppression. Overall mortality from Pneumocystis carinii pneumonia is declining, but mortality from bacterial pneumonia and mycobacterial disease is increasing. Infections with unusual and resistant organisms are also increasing. Patients with severe immunosuppression are susceptible to fungal, viral, and neoplastic pulmonary disease.

Intensive care of patients with HIV infection: utilization, critical illnesses, and outcomes. Pulmonary Complications of HIV Infection Study Group.

To examine intensive care unit (ICU) admission rates and diagnoses of patients with HIV infection, and to determine the outcomes of different critical illnesses, we analyzed data derived from the 63 patients who were admitted to an ICU from among the 1,130 adults with HIV infection who did not have AIDS at the time of enrollment in a multicenter prospective study. Patients were admitted and treated according to the judgment of their physicians. During 4,298 patient-years of follow-up for the entire cohort, there were 1,320 hospital admissions, of which 68 (5%) included admission to an ICU. Twenty-five (40%) of the patients admitted to the ICU died during that admission. Twenty-four patients (38%) were admitted with a principal diagnosis of lung disease; 11 had Pneumocystis carinii pneumonia (PCP), one of whom was coinfected with Aspergillus fumigatus and Legionella pneumophilia, and six of them (55%) died. Four had bacterial pneumonia, two had pulmonary edema caused by renal failure, and one each had pulmonary tuberculosis, pulmonary Kaposi's sarcoma, pneumothorax, adult respiratory distress syndrome, severe pulmonary fibrosis, cytomegalovirus pneumonitis, and metastatic adenocarcinoma to the lungs. Eleven of these 14 patients (79%) died. Thirty-nine patients had 44 admissions for nonpulmonary diagnoses, including gastrointestinal disorders (14 admissions), cardiovascular disorders (nine), sepsis syndrome (six), neurologic disorders (four), monitoring and ICU nursing care during or after a procedure (four), metabolic disorders (three), trauma (two), drug overdose (one), and unknown reasons (one). Nine (23%) of these patients died. Twenty-eight patients underwent mechanical ventilation, and 16 (57%) died. Seven (25%) had PCP (five died), seven had other primary pulmonary diseases (six died), and 14 were placed on mechanical ventilation for nonpulmonary disorders (five died). Survival did not correlate with CD4 count determined within 6 mo of admission to the ICU. In conclusion, the range of indications for critical care in patients with HIV infection is diverse. PCP accounted for only 16% of the ICU admissions, and mechanical ventilation for PCP and other pulmonary disorders was associated with a high mortality rate. In contrast, mechanical ventilation for nonpulmonary disorders, and admission to the ICU for nonpulmonary diagnoses was associated with a more favorable outcome.

Lymphocytic interstitial pneumonitis and nonspecific interstitial pneumonitis.

Nonspecific interstitial pneumonitis (NIP) and lymphocytic interstitial pneumonitis (LIP), with or without lymphocytic alveolitis, are poorly understood pulmonary complications of HIV infection. These disorders probably represent a spectrum of lymphoproliferative processes that overlap, rather than distinct illnesses. The clinical presentation, radiographic findings, and physiologic abnormalities in NIP and LIP are not specific and therefore require a biopsy for definitive diagnosis. The clinical course of these illnesses is generally favorable, even without specific treatment.

Prediction of tumour hypoxia and radioresistance with nuclear medicine markers.

Second-generation nuclear medicine markers of tumour hypoxia have been synthesised and screened for hypoxic marking activity in cell cultures and in mouse tumours (EMT-6). Markers of the iodinated azomycin nucleoside class with greater water solubility and faster plasma clearance rates relative to iodoazomycin arabinoside (IAZA) were of particular interest. The test systems used to characterise hypoxic marking activity of compounds included (1) covalent linkage of radiolabelled markers to cells in suspension culture equilibrated with specific O2 concentrations; (2) biodistribution of radiolabelled markers in EMT-6 tumour-bearing mice; and (3) biodistribution in R3327-AT tumour-bearing rats by nuclear medicine procedures. Of the iodinated azomycin nucleosides produced to date, beta-D-iodoazomycin galactoside (beta-D-IAZG) and beta-D-iodoazomycin xylopyranoside (beta-D-IAZXP) exhibited high metabolism-dependent hypoxic cell uptake, rapid clearance kinetics from the blood and excellent tumour marking activity in vivo. Tumour-blood (T/B) ratio (a measure of tumour hypoxic fraction) was dependent upon EMT-6 tumour size and implantation site. The radioresistance of individual tumours was measured by in vivo/in vitro assay and correlated well with the T/B ratio of hypoxic marker. These studies have identified beta-D-IAZG and beta-D-IAZXP as effective hypoxic markers for planar and single photon emission computerised tomography (SPECT) imaging studies of tumour oxygenation.

Respiratory infections in patients with HIV infection.

Changes in epidemiology have influenced the spectrum of pulmonary diseases in HIV-infected populations. The increasing proportion of patients with AIDS who are intravenous drug users and members of racial or ethnic minorities correlate with increasing cases of bacterial pneumonia and tuberculosis. Both of these infections also occur more frequently with advanced immunosuppression. Antipneumocystis prophylaxis is also reducing the incidence and mortality rate from this infection, but when respiratory failure occurs with Pneumocystis carinii pneumonia, the mortality rate is high. Immunosuppression due to HIV causes active tuberculosis in many, and tuberculosis appears to accelerate the course of HIV disease. Directly observed therapy of tuberculosis has made a major impact on the incidence and cure rates of tuberculosis in areas of high prevalence. Pulmonary disease has been a major cause of illness and death in patients with HIV infection since the beginning of the AIDS epidemic. Early in the epidemic, P. carinii pneumonia was considered the predominant pulmonary disorder. However, epidemiologic shifts and advances in treatment have broadened our perspective on the diseases that patients with HIV infection develop.

Lack of usefulness of radiographic screening for pulmonary disease in asymptomatic HIV-infected adults. Pulmonary Complications of HIV Infection Study Group.

OBJECTIVE: To determine the use of chest radiographs in the screening of asymptomatic adults infected with the human immunodeficiency virus (HIV). METHODS: A prospective, multicenter study of the pulmonary complications of HIV infection in a community-based cohort of persons with and without HIV infection. The subjects included 1065 HIV-seropositive subjects without the acquired immunodeficiency syndrome at the time of enrollment: 790 homosexual men, 226 injection drug users, and 49 women with heterosexually acquired infection. Frontal and lateral chest radiographs were performed at 3-, 6-, and 12-month intervals, CD4 lymphocyte measurements at 3- and 6-month intervals, tuberculin and mumps skin tests at 12-month intervals, and medical histories and physical examinations at 3- and 6-month intervals. Pulmonary diagnoses that occurred within 2 months following each radiograph were analyzed and correlated with the radiographic results. RESULTS: Evaluable screening chest radiographs (5263) were performed in HIV-seropositive subjects while they were asymptomatic; of these, 5140 (98%) were classified as normal and 123 (2%) as abnormal. A new pulmonary diagnosis was identified within 2 months following a screening radiograph in 55 subjects. Only 11 of these subjects had abnormal radiographs; the sensitivity of the radiograph was 20%. The sensitivity was similarly low at baseline, within each transmission category, and in subjects whose CD4 lymphocyte counts were less than 0.2 x 10(9)/L (200/microL). The types of pulmonary diseases that occurred were similar in the subjects with normal and abnormal screening radiographs. CONCLUSION: Screening chest radiography in asymptomatic HIV-infected adults is unwarranted because the diagnostic yield is low.

Traumatic injury to the azygous vein: case report.

Injury to the azygous vein is rare in blunt chest trauma. A review of the world's literature revealed only 10 cases of trauma-related azygous vein injury. We report another patient who survived azygous vein rupture secondary to thoracic rib injury. With prompt recognition, emergency thoracotomy and proper therapy, patients with azygous vein injury have a high survival rate.

Flow study of coronary-coronary bypass grafting.

Coronary-coronary bypass grafting was recently introduced for patients with either calcification of the ascending aorta or an inadequate length of graft. Flow in the coronary-coronary bypass graft and that in aortocoronary bypass to the same coronary bed was compared in eight mongrel dogs. Flow reserve of the proximal right coronary artery as a donor vessel to the coronary-coronary bypass graft was also measured. Both a coronary-coronary and aortocoronary bypass were constructed to the proximally ligated left anterior descending artery. The flow in each graft was measured with the other graft temporarily occluded. Flow reserve of the right coronary artery (mean internal diameter 1.5mm) proximal to the anastomosis was measured before and after opening of the coronary-coronary bypass. Mean(s.d.) flow as 50.0(12.3) ml/min in the coronary-coronary bypass graft and 54.9(14.8) ml/min in the aortocoronary bypass, which was not significantly different. Flow curve studies demonstrated early systolic flow reversal in the aortocoronary bypass, while the coronary-coronary bypass showed only forward flow. Mean(s.d.) flow in the proximal right coronary artery increased from 35.4(11.8) to 76.0(15.3) ml/min after opening the coronary-coronary bypass graft, which had a flow rate of 42.2(10.4) ml/min. It is concluded that the coronary-coronary bypass graft can provide nearly the same flow rate as aortocoronary bypass, and that the proximal right coronary artery has sufficient flow reserve for this technique.

Lack of efficacy of intrapleural bupivacaine for postoperative analgesia following thoracotomy.

Intrapleural bupivacaine has been reported to be effective for analgesia following cholecystectomy and thoracic surgery. Twenty patients who had a posterolateral thoracotomy were studied in a randomized, double-blind, placebo-controlled fashion. Patients were assigned to receive intrapleural administration of either 0.5 percent bupivacaine or saline solution every 4 h for 12 doses postoperatively, as well as narcotic analgesics as needed for additional pain control. Pain was assessed using a visual analogue scale. Narcotic analgesic use, duration of hospitalization, and the development of complications were recorded. There were nine evaluable patients who received bupivacaine, and ten patients who received placebo. The age, sex, and type of operation were similar in the two groups, and the procedures were performed by the same two surgeons. The mean pain score at 24 h postoperatively was 5.8 +/- 0.8 in the bupivacaine group and 6.0 +/- 0.6 in the placebo group. At 48 h, the scores were 4.6 +/- 0.8 in the bupivacaine group and 5.1 +/- 0.9 in the placebo group. The mean dose of morphine sulfate or equianalgesic dose of meperidine during the first 24 h was 13.9 +/- 3.7 mg in the bupivacaine group and 12.6 +/- 1.8 mg in the placebo group, and during the next 24 h it was 40.0 +/- 13.4 mg in the bupivacaine group and 38.0 +/- 9.2 mg in the placebo group. The mean duration of hospitalization was 12.8 +/- 3.2 days in the bupivacaine group and 12.1 +/- 2.9 days in the placebo group. Two patients who received bupivacaine and three patients who received placebo had development of pneumonia or atelectasis postoperatively. There was no statistically significant difference in any parameter between those who received bupivacaine and those who received placebo. Thus, there was no subjective or objective clinical benefit of this method of postoperative analgesia compared with placebo following posterolateral thoracotomy.