Efficacy of nilutamide as secondary hormonal therapy in androgen-independent prostate cancer

OBJECTIVE: To evaluate the activity of nilutamide as secondary hormonal therapy in patients with androgen-independent prostate cancer (AIPC), as treatment options are limited for these patients and secondary hormonal therapy with antiandrogens has advantages, including low toxicity, oral administration and high patient acceptance. PATIENTS AND METHODS: We retrospectively identified 45 patients with AIPC who were treated with nilutamide as secondary hormonal therapy in two institutions. The decrease in prostate-specific antigen (PSA) levels, side-effects of treatment, and the relationship between baseline characteristics, type and duration of previous therapy and response to nilutamide were assessed. Most patients received oral nilutamide at 150 mg/day. RESULTS: Eighteen of 45 evaluable patients (40%) had a PSA level decrease of > or = 50%. Responders (PSA decline > or = 50%) had a median (range) time to progression of 4.4 (0.31-44.7) months. There were responses to nilutamide whether used as the second to fifth line of hormonal therapy. There were no differences in response to nilutamide based on clinical stage, type of local therapy, PSA level at diagnosis or initiation of nilutamide, or type of previous antiandrogen therapy. Responders were more likely to have received monotherapy with luteinizing hormone-releasing hormone analogues or orchidectomy as first-line hormonal treatment (P = 0.02). The most common reversible adverse effects were mild to moderate visual adaptation effects, reported in 20% of patients. CONCLUSIONS: Nilutamide appears to be an effective secondary hormonal therapy in patients with AIPC and is associated with a mild toxicity profile.     

Nilutamide as second line hormone therapy for prostate cancer after androgen ablation fails

PURPOSE: We investigate the prostate specific antigen (PSA) response rate with nilutamide as a second line hormonal agent in patients with advanced prostate cancer in whom androgen ablation failed. MATERIALS AND METHODS: From 1998 to 2001, 28 patients with hormone resistant prostate cancer were treated with nilutamide as second line hormonal therapy. Average patient age +/- SD was 72.9 +/- 9.1 years. Median time from diagnosis of cancer to hormone failure was 48 months (range 2 to 120). Median followup from initiation of nilutamide therapy was 26 months (range 15 to 44). All patients had previously received at least 1 antiandrogen (flutamide or bicalutamide) in addition to medical or surgical castration, which failed. RESULTS: Upon initiation of nilutamide therapy 18 of the 28 patients (64%) had an initial reduction in PSA and 8 (29%) sustained a PSA response (greater than 50% decrease) beyond 3 months (range 3 to 21). PSA response to nilutamide in patients with a previous antiandrogen withdrawal response versus nonresponse was 100% and 18%, respectively. In 10 of the 28 patients, (36%) PSA continued to increase. Interstitial pneumonitis developed, in 1 patient and 5 had nonspecific complaints (headaches, nausea, dizziness). During followup 6 of the 28 patients died 1 of whom was a nilutamide responder. No patient died while on nilutamide. CONCLUSIONS: Nilutamide can achieve a significant sustained PSA response with a favorable toxicity profile. Patients with a previous antiandrogen withdrawal response have a significantly greater chance of responding to nilutamide.     

Nilutamide: possible utility as a second-line hormonal agent

Objectives. To study the ability of nilutamide to induce prostate-specific antigen (PSA) responses in patients with hormone-resistant prostate cancer who had been exposed to prior antiandrogen therapy, because resistance to antiandrogens may be mediated by altered binding to a mutated or overexpressed androgen receptor and because an alternative antiandrogen may overcome such resistance. Nilutamide is a little used antiandrogen that has a chemical structure distinct from that of the other two antiandrogens, flutamide and bicalutamide.Methods. Fourteen patients with hormone-resistant prostate cancer were treated with nilutamide 150 mg/day (n = 12) or 300 mg/day (n = 2). Seven had been treated with one prior antiandrogen (all with bicalutamide), five with both bicalutamide and flutamide, and two had received bicalutamide and prior chemotherapy.Results. In a retrospective analysis, 7 (50%) of the 14 patients had a greater than 50% decline in their PSA level, and 4 of the 6 patients with bone pain experienced subjective improvement. The median duration of the PSA response was 11 months (range 2 to 28+) with 2 of the 7 patients still experiencing a PSA response. In addition, 3 patients (20%) had brief and minor PSA responses (less than 50%).Conclusions. A subset of patients, whose disease progresses with prior antiandrogen therapy, may experience a PSA response to nilutamide. The role of nilutamide in such hormone-resistant patients deserves additional prospective study.     

A phase II study of nilutamide in men with prostate cancer after the failure of flutamide or bicalutamide therapy

OBJECTIVE: To determine the prostate-specific antigen (PSA) response and time to PSA or radiographic progression in men with prostate cancer refractory to bicalutamide and/or flutamide therapy. PATIENTS AND METHODS: Men with histologically confirmed prostate cancer not amenable to curative surgery or radiation therapy were eligible for the study if they had radiographic or PSA progression on at least one antiandrogen (not nilutamide) despite continued androgen suppression and standard antiandrogen withdrawal periods. All men received nilutamide 150 mg/day orally for > or = 8 weeks unless there was unacceptable toxicity or disease progression. All men were evaluated for response, safety and toxicity. Baseline PSA levels, chest X-ray, bone scan and abdominopelvic computed tomography studies were obtained; the re-evaluation included PSA levels every 4 weeks and repeated imaging every 8 weeks in those with baseline abnormalities. The chest X-ray was repeated if there were pulmonary symptoms. Nineteen men were consented and 16 were evaluable for response. RESULTS: The median (range) Gleason score was 7 (6-9) and the median number of previous second-line therapies was 2 (1-4). Bicalutamide therapy had failed in all patients. At baseline, 13 (of 16 men) had radiographically evident disease, nine with diffuse osseous and four with radiographically measurable metastases. There was no grade 3/4 toxicity; the commonest grade 1/2 toxicities were constipation (three), sensory neuropathy (four), fatigue (six), and visual changes (two) involving transiently altered colour vision and sensitivity to light, respectively. Responses included three partial and 13 with progressive disease. CONCLUSIONS: The study was discontinued after a planned interim analysis because nilutamide had no apparent activity. Although well tolerated, nilutamide offers benefit to few men with prostate cancer in whom bicalutamide has failed.     

Long-Term Efficacy and Safety of Nilutamide Plus Castration in Advanced Prostate Cancer, and the Significance of Early Prostate Specific Antigen Normalization

Purpose

We studied the long-term efficacy and tolerability of nilutamide, a nonsteroidal antiandrogen, combined with orchiectomy in patients with advanced prostate cancer.

Materials and Methods

A large double-blind trial was done on 457 patients randomized to received nilutamide or placebo after orchiectomy.

Results

At 8.5 years of followup significant benefits were found for progression and survival in favor of patients receiving nilutamide and orchiectomy. In addition, normalized prostate specific antigen levels at 3 months from the start of therapy were predictive of good long-term outcome. Moreover, combined androgen blockade with nilutamide increased the chance of patients having normal prostate specific antigen levels at 3 months. Nilutamide was well tolerated in the long term with no increase in the incidence of drug specific adverse events.

Conclusions

With long-term followup of patients with advanced prostate cancer, the combination of nilutamide and orchiectomy has significant benefits in interval to progression and improved survival compared to orchiectomy and placebo.     

Clinical significance of anti-GM-CSF antibodies in idiopathic pulmonary alveolar proteinosis

BACKGROUND: The role of anti-granulocyte-macrophage colony stimulating factor (GM-CSF) antibodies as a diagnostic marker in idiopathic pulmonary alveolar proteinosis (iPAP) remains unclear. METHODS: Anti-GM-CSF antibodies were detected in blood and bronchoalveolar lavage fluid (BAL) fluid in 13 patients with iPAP. Three patients with secondary PAP, 35 with other pulmonary disorders, and 10 subjects without lung lesions acted as controls. Blood samples only were obtained from 30 healthy medical personnel. Anti-GM-CSF antibodies were detected using immunoblotting and measured semi-quantitatively by serial dilution or concentration methods. The relationship between antibodies and reported severity indicators for iPAP was analysed. RESULTS: Anti-GM-CSF antibodies could be detected in both blood and BAL fluid samples in 12 of 13 iPAP patients and were undetectable in blood and/or BAL fluid from the other subjects studied. BAL fluid levels of anti-GM-CSF antibodies were highly correlated with the severity indicators for iPAP, including serum lactate dehydrogenase (LDH) levels, arterial oxygen tension, alveolar-arterial oxygen tension difference, (AaPO2), lung carbon monoxide transfer factor, and some lesion scores on chest radiographs and computed tomographic scans. In contrast, blood anti-GM-CSF antibodies were not significantly correlated with the severity indicators evaluated. In addition, patients with iPAP who required subsequent therapeutic lung lavage had significantly higher values of serum LDH, AaPO2, and BAL fluid anti-GM-CSF antibodies, and significantly lower values of PaO2. CONCLUSIONS: In addition to serum LDH levels, PaO2 and AaPO2, BAL fluid levels of anti-GM-CSF antibodies might reflect disease severity in patients with iPAP and predict the need for subsequent therapeutic lung lavage. These findings may expand the role of anti-GM-CSF antibodies in iPAP.     

Antiandrogen, vaccine and combination therapy in patients with nonmetastatic hormone refractory prostate cancer

PURPOSE: There is no current standard treatment for patients with prostate cancer who have received hormonal therapy but have an increasing prostate specific antigen (PSA) without radiographic evidence of metastasis. This trial was designed to analyze toxicity, immunogenicity and time to treatment failure using vaccine, antiandrogen therapy or their sequential use. MATERIALS AND METHODS: A total of 42 patients were randomized to receive vaccine vs antiandrogen therapy with nilutamide. The vaccine consisted of recombinant vaccinia viruses containing the PSA and B7.1 costimulatory genes as prime vaccinations, and avipox-PSA as boosters. After 6 months patients with an increasing PSA and no metastasis may receive a combination of both treatments. RESULTS: Three patients on nilutamide were removed from study secondary to grade 3 toxicities but no grade 3 toxicities were attributed to vaccine. In the vaccine arm median time to treatment failure was 9.9 months with 13 of 21 decreases in PSA velocity vs 7.6 months with 16 of 21 decreases in PSA velocity in the nilutamide arm (p =0.28). Of the patients in the nilutamide arm 8 had vaccine added at the time of PSA progression. Median time to treatment failure with combined therapy was 5.2 months, with a median duration from study entry of 15.9 months. Of the patients in the vaccine arm 12 had nilutamide added at the time of PSA progression. Median time to treatment failure with combined therapy was 13.9 months and a median of 25.9 months from initiation of therapy. CONCLUSIONS: Further studies are merited to investigate the role of combining vaccine with antiandrogen therapy or vaccine followed by vaccine plus antiandrogen therapy in this patient population.     

Relationships between radiographic change, pulmonary function, and bronchoalveolar lavage fluid lymphocytes in farmer's lung disease

Ninety four dairy farmers were investigated by chest radiography, pulmonary function tests, and bronchoalveolar lavage. They were divided into five groups--1: 11 subjects with acute farmer's lung; 2: 25 subjects with previously diagnosed farmer's lung who had stayed on their farm; 3: 15 farmers with previously diagnosed farmer's lung who had left the farm; 4: 23 precipitin positive symptomless farmers; 5: 20 precipitin negative symptomless farmers. The study evaluated the relationships between radiographic changes measured with a scoring system derived from the International Labour Office (ILO) classification, the results of pulmonary function tests, and bronchoalveolar lavage fluid. Thirty eight subjects had radiographic evidence of interstitial pulmonary infiltrates. Group 1 had the highest percentage of lymphocytes recovered by bronchoalveolar lavage (mean 66.3 (SD 19.2]. For all subjects carbon monoxide transfer factor (TLCO) and total lung capacity were negatively correlated with radiographic changes (r = -0.45 and -0.30; p less than 0.001 and less than 0.01 respectively). TLCO was also negatively correlated with radiographic change in group 2 (r = -0.59, p less than 0.005). The percentage of lavage lymphocytes was correlated with radiographic changes for all subjects (r = 0.36, p less than 0.001), but this correlation was not seen within groups. This study shows good correlation between radiographic abnormalities, pulmonary function changes and the cellular composition of bronchoalveolar lavage fluid.     

Interstitial pulmonary fibrosis with and without associated collagen vascular disease: results of a two year follow up.

BACKGROUND: Interstitial pulmonary fibrosis is a disease with a highly variable clinical course. To ascertain if an inadequate selection of patients might explain part of this variability, two different groups of patients with interstitial pulmonary fibrosis, those with the "lone" form of the disease (LIPF) and those with associated collagen vascular disorders (AIPF), were studied separately. METHODS: Twenty consecutive patients (nine with LIPF and 11 with AIPF) were included. Their clinical and radiographic findings and results of pulmonary function tests, gallium-67 lung scanning, and cellular analysis of bronchoalveolar lavage fluid were compared at diagnosis. Moreover, the evolution of LIPF and AIPF was contrasted after a follow up of two years, both groups having received a similar treatment regimen of corticosteroids. RESULTS: At enrollment, patients with LIPF and AIPF were of similar age, and had similar symptoms and derangement of lung function, but patients with LIPF presented with finger clubbing, more obvious radiographic abnormalities, and a greater percentage of eosinophils in bronchoalveolar lavage fluid. Two years later, patients with LIPF had significantly decreased FVC, FEV1, TLC, TLCO, and PaO2. By contrast, lung function remained unaltered in patients with AIPF. Similarly, when the percentage change from entry to the study was compared, patients with LIPF showed a significant decrease in FVC, FEV1, and PaO2. CONCLUSIONS: Unlike the patients with AIPF, those with LIPF showed a deterioration in lung function and developed further restrictive impairment and poorer gas exchange. This has implications in their clinical management.     

Pulmonary contusions: quantifying the lesions on chest X-ray films and the factors affecting prognosis.

OBJECTIVES: To quantify pulmonary contusions on chest x-ray film and to evaluate factors correlating with the size of the pulmonary contusions, changes in the first 24 hours, the need for ventilatory assistance, and death. METHODS: The medical records and chest x-ray films of 103 patients with blunt chest trauma diagnosed as having a pulmonary contusion were reviewed. RESULTS: A pulmonary contusion score was developed (3 = one third of a lung; 9 = an entire lung). In the emergency department, pulmonary contusions were not present in 11, were mild (one ninth to two ninths of a lung) in 15 patients, moderate-severe (three ninths to nine ninths of a lung) in 53 patients, and very severe in 24 patients. Within 24 hours, the pulmonary contusion score increased in 26 patients by 7.9 +/- 5.5 (SD). The 26 patients with an increasing contusion had a higher mortality rate (38% vs. 17%) (p = 0.044) and tended to need ventilatory assistance more frequently (73% vs. 49%) (p = 0.061). The 35 patients with very severe pulmonary contusions (pulmonary contusion score = 10-18) had the lowest PaO2:FIO2 ratio at 24 hours (175 +/- 103 mm Hg), longest hospital length of stay (28 +/- 35 days), and the highest Injury Severity Score (26 +/- 9). The factors correlating highest with a need for ventilatory support (57/103) were the 24 hour or initial PaO2/FIO2 ratio < 300, an Injury Severity Score > or = 24, Revised Trauma Score < 6.4, Glasgow Coma Scale score < or = 12, and shock or need for blood in the first 24 hours (p < 0.001). Death correlated highly with a need for ventilatory assistance, Injury Severity Score > or = 26, Revised Trauma Score < or = 6.3, and Glasgow Coma Scale score < or = 11 (p < 0.001). CONCLUSION: Quantifying and noting changes in the extent of the pulmonary contusions and PaO2/FIO2 ratio during the first 24 hours may be of value in determining the need for ventilatory assistance and predicting outcome.     

Video-assisted thoracoscopic surgery does not deteriorate postoperative pulmonary gas exchange in spontaneous pneumothorax patients.

OBJECTIVES: Video-assisted thoracoscopic surgery (VATS) is generally recognized as a less invasive method than thoracotomy. However, the influence of VATS on postoperative pulmonary gas exchange has yet to be evaluated. METHODS: Thirty eight patients with spontaneous pneumothorax were randomized into bullectomy by VATS (n = 20) or axillary thoracotomy (n = 18). Gas exchange was assessed by using hot wire mass spectrometer, and blood gas analysis preoperatively and postoperatively at 1, 3, 6, 12, 24, and 48 h and on days 4 and 6. Post operative pain control was managed by continuous epidural morphine injection and administration of diclofenac sodium orally or suppository. Postoperative atelectasis was assessed by daily chest roentgenograms. RESULTS: VATS patients had continuously higher PaO2 than axillary thoracotomy at 12, 48 h and day 4 postoperatively (P < 0.05). Alveolar-arterial oxygen tension gradient in VATS patients was significantly less than that in patients with axillary thoracotomy from the 6th h throughout to the 4th day postoperatively (P < 0.01). Use of postoperative analgesics and the incidence of peripheral atelectasis were more frequent in patients with axillary thoracotomy. CONCLUSIONS: Bullectomy via VATS was less deleterious to pulmonary gas exchange. Axillary thoracotomy caused worsening of gas exchange postoperatively due to incisional pain, chest wall deformity, and peripheral atelectasis.     

Pulmonary Infections in Intestinal Transplant Recipients With Preexisting Pulmonary Nodules

BackgroundPulmonary nodules in asymptomatic patients could represent latent pulmonary infections. Intestinal transplant (ITx) recipients with preexisting lung nodules might be at higher risk for pulmonary infections. However, data is scarce.MethodsThis retrospective study included adult patients who underwent ITx from May 2016 to May 2020. Chest computed tomography scans performed within 12 months before ITx were obtained to evaluate for preexisting pulmonary nodules. Screening for endemic mycoses, Aspergillus, Cryptococcus, and latent tuberculosis infection performed within 12 months before ITx was obtained. We assessed for worsening pulmonary nodules, and fungal and mycobacterial infections during the first year post-transplant. Survival and graft loss at 1-year post-transplant was also assessed.ResultsForty-four patients underwent ITx. Thirty-one had preexisting lung nodules. No invasive fungi were recorded in the pretransplant period and one individual had latent tuberculosis infection. In the post-transplant period, one individual developed probable invasive aspergillosis and had worsening nodular opacities, whereas one had disseminated histoplasmosis with stable lung nodules in chest computed tomography. No mycobacterial infections were documented. The cohort survival was 84% at 12 months after transplant.ConclusionPreexisting pulmonary nodules were common in the cohort (71%), yet latent and active pulmonary infections were rare. Appearance of new or worsening pulmonary nodules does not appear to directly correlate with pulmonary infections in the post-transplant period. Routine chest computed tomography is not recommended in the pretransplant period, but follow-up is favored in patients with confirmed nodular opacities. Clinical monitoring is essential.     

Modelling thirty-day mortality in the Acute Respiratory Distress Syndrome (ARDS) in an adult ICU

Variables predicting thirty-day outcome from Acute Respiratory Distress Syndrome (ARDS) were analysed using Cox regression structured for time-varying covariates. Over a three-year period, 1996-1998, consecutive patients with ARDS (bilateral chest X-ray opacities, PaO2/FiO2 ratio of <200 and an acute precipitating event) were identified using a prospective computerized data base in a university teaching hospital ICU. The cohort, 106 mechanically ventilated patients, was of mean (SD) age 63.5 (15.5) years and 37% were female. Primary lung injury occurred in 45% and 24% were postoperative. ICU-admission day APACHE II score was 25 (8); ARDS onset time from ICU admission was 1 day (median: range 0-16) and 30 day mortality was 41% (95% CI: 33%-51%). At ARDS onset, PaO2/FiO2 ratio was 92 (31), 81% had four-quadrant chest X-ray opacification and lung injury score was 2.75 (0.45). Average mechanical ventilator tidal volume was 10.3 ml/predicted kg weight. Cox model mortality predictors (hazard ratio, 95% CI) were: APACHE II score, 1.15 (1.09-1.21); ARDS lag time (days), 0.72 (0.58-0.89); direct versus indirect injury, 2.89 (1.45-5.76); PaO2/FiO2 ratio, 0.98 (0.97-0.99); operative versus non-operative category, 0.24 (0.09-0.63). Time-varying effects were evident for PaO2/FiO2 ratio, operative versus non-operative category and ventilator tidal volume assessed as a categorical predictor with a cut-point of 8 ml/kg predicted weight (mean tidal volumes, 7.1 (1.9) vs 10.7 (1.6) ml/kg predicted weight). Thirty-day survival was improved for patients ventilated with lower tidal volumes. Survival predictors in ARDS were multifactorial and related to patient-injury-time interaction and level of mechanical ventilator tidal volume.     

Pulmonary alveolar proteinosis detected by a nodular lesion on chest computed tomography

A 74-year-old woman was admitted to our hospital for further examination of chest X-ray abnormality. The chest computed tomography (CT) revealed a nodular lesion (1.0 cm in diameter) in right lung. Bronchoscopic biopsy showed no malignant cells and bronchoalveolar lavage fluid was not milky white. We performed video-assisted thoracic surgery and a tumor was resected. Histologically, dilated alveolar areas was filled with eosinophilic materials. This finding was compatible with pulmonary alveolar proteinosis (PAP). The characteristic CT finding of PAP is ground glass opacities in both lungs with thickened alveolar septa (so-called crazy-paving appearance). The CT findings of this case (unilateral, single nodular lesion) are very rare, so we report this case with references to the literatures.     

Intraoperative pleural lavage cytology in lung cancer patients

Cytology of intraoperative pleural lavage was examined in 164 lung cancer patients who underwent pulmonary resections. None of the patients had any pleural effusion or dissemination. Cytology was performed three times: (1) at thoracotomy, (2) immediately after resection, and (3) after washing the pleural cavity with 5,000 mL of physiological saline solution just before closure of the chest wall. Twenty-three patients (14%) had more than one positive cytological finding. The frequency of positive cytological findings was significantly correlated with pathological T classification, pleural status, and pathological stage. The positive lavage group had a significantly higher recurrence rate than the negative lavage group in patients with stage I or stage II cancer. Four patients in the positive lavage group (17.4%) had recurrence in pleura or pericardium whereas only 1 patient in the negative lavage group (0.7%) had a recurrence in pericardium. The positive cytological finding of pleural lavage has more important meaning as a prognostic factor in stage I and stage II and indicates a greater possibility of recurrence in pleura or pericardium, but further examinations to evaluate the viability of detected malignant cells are required so that the positive cytological findings of pleural lavage can be regarded as subclinical pleural dissemination.     

Effect of positive end expiratory pressure on arterial oxygenation during bronchoalveolar lavage for proteinosis

To maintain good cellular oxygenation during bronchopulmonary lavage for alveolar proteinosis is often a difficult problem to solve. A case is reported of alveolar proteinosis in whom four lavages were performed. Details of the technique are discussed, as are the problems with expedients used to improve PaO2. The use of a 10 cmH2O positive end-expiratory pressure was useful only during the "in-phase"; in the "out-phase", it worsened the PaO2. PaO2 during lavage in patients with alveolar proteinosis can only be improved by three ways: cancellation of the shunt during lung filling and, during the "out-phase", an increase in FIO2 or pulmonary artery occlusion by a balloon.     

The Clinical and Physiological Effect of Whole-Lung Lavage in Pulmonary Alveolar Proteinosis: A Ten-Year Experience

We have utilized whole-lung lavage in the successful treatment of 18 patients with pulmonary alveolar proteinosis. Our ten-year experience includes serial evaluations of patients with disabling lung dysfunction who had a total of 49 whole-lung lavages under general anesthesia. Clinical and physiological responses were documented both before and after each lavage. There were no complications or deaths. All patients were radiographically, physiologically, and symptomatically improved within hours after the procedures. Five patients required from two to four repeat lavages one to three years later.The treatment of this disorder has included a wide variety of techniques. We attribute our results to the use of a lung lavage technique that includes: (1) unilateral whole-lung lavages at two to three day intervals; (2) isotonic saline as the lavage solution; (3) use of a mechanical chest percussor during lavage; and (4) measuring the total thoracic compliance of each side in the immediate postlavage period as a guide for extubation. We conclude that whole-lung lavage is a safe, highly effective, repetitively applicable treatment for pulmonary alveolar proteinosis.     

Clinicopathological correlations in cor pulmonale.

BACKGROUND: The relation between pulmonary disease and physiological abnormality in patients with hypoxic cor pulmonale is controversial and the association between arterial hypoxaemia and right ventricular hypertrophy has been challenged. To address these problems matched patients treated with and without domiciliary oxygen were studied. METHODS: Necropsy data were obtained on 19 patients (14 male), 10 of whom had been treated with domiciliary oxygen. Pulmonary artery pressure and total pulmonary vascular resistance as well as blood gas tensions during the breathing of air and oxygen were available for the six months before death. Formalin fixed lung slices were assessed for panacinar and centriacinar emphysema. Right and left ventricular weights were measured and their ratio (LV&S/RV) was used as an index of right ventricular hypertrophy. Carotid body weights were available in 14 cases. RESULTS: Fourteen patients died of respiratory failure and antemortem thrombus was found in the pulmonary arteries of eight cases. Physiological measurements were unrelated to the degree of macroscopic emphysema, pulmonary hypertension, or daytime blood gas tensions. When allowance was made for the higher "ambient" arterial oxygen tension (PaO2) of those who had oxygen, PaO2 was correlated with LV&S/RV (r = 0.79), absolute right ventricular weight (r = -0.53), and carotid body weight (r = 0.68). CONCLUSIONS: These data show that in hypoxic cor pulmonale in vivo physiological disturbances are poor indicators of the underlying disease process. The relation of "ambient" PaO2 to right ventricular hypertrophy and carotid body weight suggests that domiciliary oxygen therapy might lead to regression of such established disease.