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

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.     

Hemodynamic effects of Dextran 40 on hemorrhagic shock during hyperbaria and hyperbaric hyperoxia

Three groups of six dogs each were instrumented with an electromagnetic flow-meter around the pulmonary artery, and indwelling silastic cannulas in the pulmonary artery, the left ventricle, the ascending aorta and the right atrium. After 7-10 d, dogs were studied under normobaric conditions, breathing air, at 2.8 atmospheres absolute (ATA) breathing 100% oxygen (PO2 approximately equal to 2128 mm Hg), and at 6 ATA breathing air (PO2 approximately equal to 960 mm Hg). Baseline recordings were made at 1 ATA and repeated after arrival at depth. The dogs were hemorrhaged until the mean aortic pressure fell to 40 mm Hg. Pressure was maintained between 40-50 mm Hg for 30 min. Enough Dextran 40 was then infused to stabilize the aortic pressure to within 90% of its original 1 ATA baseline value. Hemodynamic parameters were measured or calculated at eight different times. More than twice the amount of Dextran 40 was required at depth than at 1 ATA. There were statistically significant differences due to the effects of hemorrhage but no differences between the three groups attributable to either of the hyperbaric conditions or the effects of Dextran 40.     

18F-氟赤式硝基咪唑肿瘤乏氧显像实验研究

目的 探讨18F-氟赤式硝基咪唑(FETNIM)在肿瘤乏氧诊断中的应用价值.方法 30只SPCA-1人肺腺癌荷瘤BALB/c裸鼠采用随机数字表法分为A和B 2组(鼠数分别为16和14只).尾静脉注射37 MBq18F-FETNIM后A组分别于注射后0.5,1,2,3 h处死裸鼠,取血液、肺、心、肝、脾、肾、肿瘤等组织测量质量,用γ计数仪测定放射性计数,计算每克组织百分注射剂量率(%ID/g);B组用PO2微电极测量肿瘤组织内乏氧情况.结果 18F-FETNIM在肾中代谢最高,在脂肪和骨骼中代谢较低,肿瘤/正常组织的放射性比值较高,且随时间而增加,2 h达最高,肿瘤/血液放射性比值为1.69±0.37,肿瘤/肌肉放射性比值为1.57±0.47.HE染色显示瘤内有大量的乏氧坏死组织.组织内PO2微电极测量示肿瘤内均有乏氧,肿瘤内PO,1.1～27.7 mm Hg(1 mm Hg=0.133 kPa).结论 18F-FETNIM在荷瘤裸鼠体内具有较低的外周代谢,脂溶性较低,能被肿瘤乏氧组织摄取,可用于肿瘤乏氧诊断.     

Hemodynamic effects of 10% dextrose and of dextran 70 on hemorrhagic shock during exposure to hyperbaric air and hyperbaric hyperoxia

Six groups of six conditioned dogs each were instrumented with an electromagnetic flow-meter transducer around the pulmonary artery, and indwelling silastic cannulae in the pulmonary artery, the left ventricle, the ascending aorta, and the right atrium. After allowing a minimum of 5 d for recovery, the dogs were studied under normobaric conditions, breathing air, at 2.8 atmospheres absolute (ATA), breathing 100% oxygen (PO2 2128 mm Hg) and at 6 ATA breathing air (PO2 960 mm Hg). Baseline recordings were made at 1 ATA and repeated after arrival at depth. The dogs were hemorrhaged until the mean aortic pressure fell to 40 mm Hg. Mean aortic pressure was maintained between 40-50 mm Hg for 30 min. This required a rather constant 40 +/- 4.5 ml X kg-1 body weight of total blood removed. Three groups, one at each depth perturbation, were then given Dextran 70, the other three groups 10% dextrose. Fluids were administered at a constant rate until the mean aortic pressure rose to within 90% of its original 1 ATA baseline value. At this point, the infusion was stopped and the total amount of fluid administered was recorded. Hemodynamic parameters were measured or calculated for eight different time periods during each experiment. The amount of Dextran 70 required did not change with hyperbaric exposure but only half as much 10% dextrose was required at depth. Dextran 70 held the cardiovascular parameters constant for 30 min following administration but after 10% dextrose, cardiac output tended to decrease at 15 and 30 min posttreatment. There were no significant differences in the cardiovascular effects of hemorrhage between or among the dogs exposed to the three different environmental conditions.     

Diagnosis of tumors of the parotid gland with anti-CEA immunoscintigraphy

Twenty-nine consecutive patients with a palpable unilateral tumor in the parotid gland region had scintigraphy 22-28 hr after they were injected with 111In-labeled monoclonal anti-carcinoembryonic antigen (CEA) antibody (F023C5). Two patients were imaged at 48 hr also, and one patient was imaged additionally with single-photon emission CT. Twenty-seven of the patients had surgery within 2-3 weeks. The serum CEA concentrations were normal in 27 of 29 patients. Immunoglobulin G human anti-murine-antibody concentrations were elevated in three of 20 patients. Ten patients had scintigraphic findings suggesting a malignant tumor, six of them had histologically proved malignant tumors. The tumors associated with positive immunoscintigrams were stained immunohistochemically with anti-CEA, and four of the malignant tumors were positive in immunohistochemical staining. The results suggest that nonspecific anti-CEA-antibody imaging is helpful in predicting the presence of a malignant tumor in the parotid area. The radioantibody method could provide useful clinical information that has a high negative predictive value.     

Breast cancer imaging with mouse monoclonal antibodies

The localization of 111In-labelled MA5 monoclonal antibody, reactive with a breast tumor associated antigen, was studied in 17 patients. MA5 was selected because 1) it reacts with greater than 95% of primary and metastatic lesions, 2) the recognized antigen is present on the cell surface in vivo and 3) MA5 gives excellent localization in human breast tumor xenografts. Each patient received 2 mg antibody labeled with 5 mCi 111In and in some cases, 3 mg or 18 mg unlabeled carrier antibody. No serious allergic reactions were noted. There was a large uptake in the liver, less significant uptake in the spleen and bone, and minimal accumulation in the bowel. Bone lesions, primary tumors, soft tissue recurrences and lung metastases larger than 3 cm diameter were imaged, while only 1 lesion smaller than 3 cm was detected. Non specific accumulation of tracer was noted at the site of a port-a-cath, in a hematoma, in fibrocystic lesions, and at sites of previous radiation treatment. Extensive fibrosis and poor vascularization characteristic of breast tumors may explain in part the limited sensitivity of the imaging.     

Intratumoral distribution of radiolabeled antibody and radioimmunotherapy in experimental liver metastases model of nude mouse.

The biodistribution and intratumoral distribution of radiolabeled anticarcinoembryonic antigen (CEA) monoclonal antibody in experimental liver metastases and the therapeutic effect of 131I-labeled anti-CEA antibody on the metastases were studied. METHODS: Three weeks after an intrasplenic injection of human colon cancer cells, mice received an intravenous injection of 125I- or 111In-labeled anti-CEA antibody F33-104. The biodistribution and tumor penetration of radiolabeled antibody were examined by using quantitative autoradiography. To evaluate the therapeutic effect, 5.55, 9.25 or 11.1 MBq (150, 250 or 300 microCi) 131I-labeled F33-104 were injected into groups of mice that had micrometastases smaller than 1 mm. Control groups were injected with phosphate-buffered saline or 131I-labeled control antibody. Mice were killed 3 wk later to determine the size of liver metastases. RESULTS: 1251-labeled F33-104 showed a high accumulation in the liver metastases (percentage of injected dose per gram of metastases [%ID/g] >24%, metastasis-to-liver ratio >9.8, metastasis-to-blood ratio >2.1); however, its accumulation was heterogeneous or peripheral in the nodules more than 1 mm in diameter. When the antibody dose was increased, antibody penetration was improved, but tumor uptake of radioactivity and specificity ratios decreased. In mice with large metastases, radioactivity in the normal tissue was lower than that in mice with small metastases, resulting in higher metastasis-to-background ratios. 111In-labeled antibody showed even higher tumor uptake than 125I-labeled antibody (>51 %ID/g). Metastases formation was suppressed in a dose-dependent manner by 131I-labeled F33-104 injection (5 of 8 mice had no macroscopic tumor after an injection of 5.55 MBq (150 microCi), and all mice had no visible metastasis after an injection of 9.25 or 11.1 MBq [250 or 300 microCi]), whereas tumor progression was seen in the control groups. CONCLUSION: Liver metastases had easy accessibility to the antibody. Micrometastases of less than 0.5 mm in diameter showed homogeneous intratumoral distribution of injected antibody and were successfully treated with 131I-labeled antibody. Very high uptake and satisfactory metastasis-to-liver ratios with 111In-labeled antibody suggest that the use of a radiometal with high beta-energy, such as 90Y or 188Re, is preferable for the successful radioimmunotherapy of metastases larger than 1 mm.     

Using pullback pressure measurements to identify venous stenoses persisting after successful angioplasty in failing hemodialysis grafts

OBJECTIVE: We used pullback pressure measurements to identify venous stenoses persisting after angioplasty of failing hemodialysis grafts. MATERIALS AND METHODS: Fifty angioplasty procedures were performed in 32 patients with elevated venous pressures at dialysis. Grafts were initially evaluated on digital subtraction angiography, and all stenoses measuring greater than 50% on angiography underwent angioplasty. In successful cases (residual stenosis < 30%), pullback pressure measurements were obtained from the superior vena cava to the graft to identify hemodynamically significant (> 10 mm Hg) stenoses. These lesions were then treated with repeated angioplasty. RESULTS: Hemodynamically significant stenoses with a gradient range of 10-27 mm Hg (mean, 16 mm Hg) were found in nine (18%) of 50 procedures. All gradients occurred at sites of previous angioplasty. Repeated angioplasty of these stenoses performed with larger angioplasty balloons reduced gradients to less than 3 mm Hg in six stenoses and to 5 mm Hg in three stenoses. In this subgroup, primary patency was eight (89%) of nine stenoses at 1 month and 2 months and five (56%) of nine stenoses at 6 months. Using life table analysis, we found that primary patency of the entire population was 84% at 1 month, 66% at 2 months, and 47% at 6 months. The mean time between interventions was 6 months, and the thrombosis rate was 0.32 per year. CONCLUSION: Pullback pressure measurements are a useful adjunct to angiography to evaluate the hemodynamic results of angioplasty in patients with failing hemodialysis grafts.     

Tumor oxygenation using direct injection of oxygenated saline

Direct injection of oxygen into an in-vivo tumor system was performed using saline lavage through a double-lumen catheter inserted into a Walker 256 carcinoma implanted in the flank of a rat. Ten extremely hypoxic tumors (core pO2 0 to 1 mm Hg) were examined. The mean pO2 in these tumors increased from 66 to 112 mm Hg after 5 minutes of lavage with oxygenated saline. These results indicate a substantial increase in tumor pO2 can be obtained with this system, possibly resulting in improved radioresponsiveness. More general applications of this system may also be feasible.     

Oxygenation Measurements in Head and Neck Cancers during Hyperbaric Oxygenation

BACKGROUND: Tumor hypoxia has proven prognostic impact in head and neck cancers and is associated with poor response to radiotherapy. Hyperbaric oxygenation (HBO) offers an approach to overcome hypoxia. We have performed pO2 measurements in selected patients with head and neck cancers under HBO to determine in how far changes in the oxygenation occur and whether a possible improvement of oxygenation parameters is maintained after HBO. PATIENTS AND METHODS: Seven patients (five male, two female, age 51-63 years) with squamous cell cancers of the head and neck were investigated (six primaries, one local recurrence). The median pO2 prior to HBO was determined with the Eppendorf histograph. Sites of measurement were enlarged cervical lymph nodes (n = 5), the primary tumor (n = 1) and local recurrence (n = 1). Patients then underwent HBO (100% O2 at 240 kPa for 30 minutes) and the continuous changes in the oxygenation during HBO were determined with a Licox probe. Patients had HBO for 30 minutes (n = 6) to 40 minutes (n = 1). HBO was continued because the pO2 had not reached a steady state after 30 minutes. After decompression, patients ventilated pure oxygen under normobaric conditions and the course of the pO2 was further measured over about 15 minutes. RESULTS: Prior to HBO, the median tumor pO2 in the Eppendorf histography was 8.6 +/- 5.4 mm Hg (range 3-19 mm Hg) and the pO2 measured with the Licox probe was 17.3 +/- 25.5 mm Hg (range 0-73 mm Hg). The pO2 increased significantly during HBO to 550 +/- 333 mm Hg (range 85-984 mm Hg, p = 0.018). All patients showed a marked increase irrespective of the oxygenation prior to HBO. The maximum pO2 in the tumor was reached after 10-33 minutes (mean 17 minutes). After leaving the hyperbaric chamber, the pO2 was 282 +/- 196 mm Hg. All patients maintained an elevated pO2 for further 5-25 minutes (138 +/- 128 mm Hg, range 42-334 mm Hg, p = 0.028 vs the pO2 prior to HBO). CONCLUSIONS: Hyperbaric oxygenation resulted in a significant increase in the tumor oxygenation in all seven investigated patients. A significant increase at the point of measurement could be maintained for several minutes after decompression and after leaving the hyperbaric chamber.     

124I-labeled engineered anti-CEA minibodies and diabodies allow high-contrast, antigen-specific small-animal PET imaging of xenografts in athymic mice.

Prolonged clearance kinetics have hampered the development of intact antibodies as imaging agents, despite their ability to effectively deliver radionuclides to tumor targets in vivo. Genetically engineered antibody fragments display rapid, high-level tumor uptake coupled with rapid clearance from the circulation in the athymic mouse/LS174T xenograft model. The anticarcinoembryonic antigen (CEA) T84.66 minibody (single-chain Fv fragment [scFv]-C(H)3 dimer, 80 kDa) and T84.66 diabody (noncovalent dimer of scFv, 55 kDa) exhibit pharmacokinetics favorable for radioimmunoimaging. The present work evaluated the minibody or diabody labeled with (124)I, for imaging tumor-bearing mice using a high-resolution small-animal PET system. METHODS: Labeling was conducted with 0.2-0.3 mg of protein and 65-98 MBq (1.7-2.6 mCi) of (124)I using an iodination reagent. Radiolabeling efficiencies ranged from 33% to 88%, and immunoreactivity was 42% (diabody) or >90% (minibody). In vivo distribution was evaluated in athymic mice bearing paired LS174T human colon carcinoma (CEA-positive) and C6 rat glioma (CEA-negative) xenografts. Mice were injected via the tail vein with 1.9-3.1 MBq (53-85 microCi) of (124)I-minibody or with 3.1 MBq (85 microCi) of (124)I-diabody and imaged at 4 and 18 h by PET. Some mice were also imaged using (18)F-FDG 2 d before imaging with (124)I-minibody. RESULTS: PET images using (124)I-labeled minibody or diabody showed specific localization to the CEA-positive xenografts and relatively low activity elsewhere in the mice, particularly by 18 h. Target-to-background ratios for the LS174T tumors versus soft tissues using (124)I-minibody were 3.05 at 4 h and 11.03 at 18 h. Similar values were obtained for the (124)I-diabody (3.95 at 4 h and 10.93 at 18 h). These results were confirmed by direct counting of tissues after the final imaging. Marked reduction of normal tissue activity, especially in the abdominal region, resulted in high-contrast images at 18 h for the (124)I-anti-CEA diabody. CEA-positive tumors as small as 11 mg (<3 mm in diameter) could be imaged, and (124)I-anti-CEA minibodies, compared with (18)F-FDG, demonstrated highly specific localization. CONCLUSION: (124)I labeling of engineered antibody fragments provides a promising new class of tumor-specific probes for PET imaging of tumors and metastases.     

Beneficial effects of hypnosis and adverse effects of empathic attention during percutaneous tumor treatment: when being nice does not suffice

PURPOSE: To determine how hypnosis and empathic attention during percutaneous tumor treatments affect pain, anxiety, drug use, and adverse events. MATERIALS AND METHODS: For their tumor embolization or radiofrequency ablation, 201 patients were randomized to receive standard care, empathic attention with defined behaviors displayed by an additional provider, or self-hypnotic relaxation including the defined empathic attention behaviors. All had local anesthesia and access to intravenous medication. Main outcome measures were pain and anxiety assessed every 15 minutes by patient self-report, medication use (with 50 mug fentanyl or 1 mg midazolam counted as one unit), and adverse events, defined as occurrences requiring extra medical attention, including systolic blood pressure fluctuations (> or =50 mm Hg change to >180 mm Hg or <105 mm Hg), vasovagal episodes, cardiac events, and respiratory impairment. RESULTS: Patients treated with hypnosis experienced significantly less pain and anxiety than those in the standard care and empathy groups at several time intervals and received significantly fewer median drug units (mean, 2.0; interquartile range [IQR], 1-4) than patients in the standard (mean, 3.0; IQR, 1.5-5.0; P = .0147) and empathy groups (mean, 3.50; IQR, 2.0-5.9; P = .0026). Thirty-one of 65 patients (48%) in the empathy group had adverse events, which was significantly more than in the hypnosis group (eight of 66; 12%; P = .0001) and standard care group (18 of 70; 26%; P = .0118). CONCLUSIONS: Procedural hypnosis including empathic attention reduces pain, anxiety, and medication use. Conversely, empathic approaches without hypnosis that provide an external focus of attention and do not enhance patients' self-coping can result in more adverse events. These findings should have major implications in the education of procedural personnel.     

Plasma volume and estimated liver plasma flow during hyperbaric and hyperoxic exposures in awake dogs

Five different experiments were conducted to determine if estimated liver plasma flow and/or plasma volume were changed as a result of exposure to 2.8 atmospheres absolute (ATA) while breathing 100% oxygen or 6 ATA while breathing compressed air. The experiments were designed to separate the relative roles of the ambient pressure, the partial pressure of oxygen, the time of high oxygen exposure or some combination of these factors on any observed changes. We found that time was not a factor in the changes seen. Hyperbaria resulted in a decrease in estimated liver plasma flow at all pressures greater than 1 ATA. There was an apparent increase in plasma volume at 1.3 ATA and a return towards 1 ATA values at higher pressures. Hyperoxia resulted in a decrease in estimated liver plasma flow at 975 mm Hg but not at 912 mm Hg. The flow was then increased again at 2128 mm Hg. Plasma volume decreased significantly at 912 mm Hg returned to baseline (152 mm Hg) values at 975 mm Hg and then decreased again at 1054 and 2128 mm Hg PO2.     

Breast cancer imaging with mouse monoclonal antibodies

The localization of ¹¹¹In-labelled MA5 monoclonal antibody, reactive with a breast tumor associated antigen, was studied in 17 patients. MA5 was selected because 1) it reacts with >95% of primary and metastatic lesions, 2) the recognized antigen is present on the cell surface in vivo and 3) MA5 gives excellent localization in human breast tumor xenografts. Each patient received 2 mg antibody labeled with 5 mCi ¹¹¹In and in some cases, 3 mg or 18 mg unlabeled carrier antibody. No serious allergic reactions were noted. There was a large uptake in the liver, less significant uptake in the spleen and bone, and minimal accumulation in the bowel. Bone lesions, primary tumors, soft tissue recurrences and lung metastases larger than 3 cm diameter were imaged, while only 1 lesion smaller than 3 cm was detected. Non specific accumulation of tracer was noted at the site of a port-a-cath, in a hematoma, in fibrocystic lesions, and at sites of previous radiation treatment. Extensive fibrosis and poor vascularization characteristic of breast tumors may explain in part the limited sensitivy of the imaging.     

Intrapatient and interpatient comparison of tumor size and monoclonal antibody uptake in melanoma

In two panels totaling 52 patients with melanoma who were imaged with In-111 labeled 96.5 or ZME-018 (ZME) monoclonal antibodies (MoAb), four patients demonstrated numerous metastases (greater than or equal to 20) in the subcutaneous tissues and peripheral lymph nodes. These constituted four intrapatient groups of tumors. These were selected for an intrapatient comparison of tumor size and uptake. Data on 16 additional patients imaged with 96.5 MoAb with fewer (less than or equal to 11) such tumor foci were pooled and used as an interpatient control group of tumors. Uptake was graded 0-5+ (liver = 4+). The data were similar in all five groups. All tumors with a diameter less than 0.7 cm were not detected. All large tumors were demonstrated, usually with high uptake. Small tumors (greater than or equal to 0.7 cm in diameter), however, showed variable uptake, from 0-4+. Thus, tumors within one patient were as variable in uptake as tumors between patients. Immunologic studies of melanoma tumor antigens have shown a similar variability. It is suggested that antigenic heterogeneity is responsible for the variable scintigraphic demonstration of such tumors.     

Melanoma localization in nude mice with monoclonal Fab against p97

The tumor targeting capacity of monoclonal antibody Fab fragments was explored in nude mice bearing human melanoma xenografts. Radioiodinated Fab 8.2 and 96.5, specific for melanoma-associated antigen p97, were tested in vitro for immunoreactivity and in vivo for tumor localization relative to a co-administered control, Fab 1.4. Fab was cleared rapidly from the blood with a T1/2 of 3-3.5 hr and greater than 90% of the injected radioactivity was excreted by 16 hr. The mean specific Fab in tumor reached a maximum of 3.5% injected dose/g at 4 hr and decreased to 1.5% at 16 hr. Over the same period, the ratio of specific/control Fab in tumor normalized to blood, the localization index, rose from 3 to 25 compared with ratios near unity for all other tissues. The concentration of specific Fab in tumor could be correlated to the amount of Fab protein administered as well as its immunoreactivity.     

Training improves divers' ability to detect increased CO2

BACKGROUND: Elevated arterial PCO2 (hypercapnia) is a known risk in diving with closed circuit breathing apparatus. In a retrospective study, we determined CO2 retention and the ability to detect CO2 in novice divers who were either CO2-recognition-trained subjects (TS) or untrained subjects (UTS). METHODS: Ventilatory and perceptual responses to variations in inspired CO2 (range 0-5.6 kPa, 0-42 mm Hg) during moderate exercise were assessed in novice Israeli Navy divers on active duty. Tests were carried out on 231 TS and 213 UTS. RESULTS: The minimal mean inspired PCO2 that could be detected was 4.8 +/- 1.6 kPa (36 +/- 12 mm Hg) in UTS and 2.9 +/- 0.7 kPa (22 +/- 5 mm Hg) in TS (p < 0.0001). No significant changes were found in PETCO2 between the two groups during exposure to a PICO2 of 5.6 kPa (42 mm Hg). There were 46 TS who were found to be CO2 retainers (more than +1 SD above the mean) and 19 were classified as poor detectors (more than +1 SD above the mean). Seven subjects exhibited both traits. During actual oxygen diving performed later by this group, the only four cases of CNS-oxygen toxicity were among those seven subjects (p < 0.01). CONCLUSIONS: We conclude that CO2 recognition training improves the diver's capability to detect CO2. We suggest that a diver who is both a poor CO2 detector and a CO2 retainer will be prone to CNS-oxygen toxicity.     

Chest radiographs in congestive heart failure: response to therapy in acute and chronic heart disease

Thirty-four men with left ventricular mechanical dysfunction were admitted to an intensive care unit with either an acute myocardial infarction (Group 1, n = 18) or worsening of clinical respiratory signs and symptoms in the setting of a chronic congestive cardiomyopathy (Group 2, n = 16). On admission, all individuals had pulmonary venous hypertension classified as at least Grade 3 by standard radiographic criteria. In each subject, mean pulmonary capillary wedge pressure (mm Hg), extravascular lung water (EVLW) (ml/kg), and chest radiographs were serially evaluated. In the patients in whom pharmacologic therapy successfully returned left ventricular filling pressures to near normal levels (less than or equal to 15 mm Hg), the chest radiograph returned to its baseline level (defined by the discharge radiograph) later in the patients with chronic heart failure (5.1 +/- 1.0 days) than in the patients with acute myocardial infarctions (2.1 +/- 1.2 days, p less than 0.01). Radiographic changes in extravascular water (interstitial and alveolar edema) mirrored changes in EVLW, although EVLW was initially greater in Group 2 (16.3 +/- 1.8 ml/kg) than in Group 1 (10.7 +/- 1.3 ml/kg, p less than 0.01). In the patients in whom filling pressures either worsened or changed less than 3 mm Hg, EVLW and chest radiographs did not markedly change. It is concluded that changes in radiographic pulmonary edema mirror changes in indicator-dilution measurements of EVLW. Radiographic phase lag represents a slow decline in EVLW after therapy for heart failure, which is prolonged in patients with chronic failure and greater EVLW.     

Tumor uptake of copper-diacetyl-bis(N(4)-methylthiosemicarbazone): effect of changes in tissue oxygenation.

We showed previously that, in vitro, copper-diacetyl-bis(N(4)-methylthiosemicarbazone) (Cu-ATSM) uptake is dependent on the oxygen concentration (pO2). We also showed that, in vivo, Cu-ATSM uptake is heterogeneous in animal tumors known to contain hypoxic fractions. This study was undertaken to confirm the pO2 dependence of this selective uptake in vivo by correlating Cu-ATSM uptake with measured tumor pO2. METHODS: Experiments were performed with the 9L gliosarcoma rat model using a needle oxygen electrode to measure tissue pO2. Using PET and electronic autoradiography, Cu-ATSM uptake was measured in tumor tissue under various pO2 levels. The oxygen concentration within implanted tumors was manipulated by chemical means or by altering the inhaled oxygen content. RESULTS: A good correlation between low pO2 and high Cu-ATSM accumulation was observed. Hydralazine administration in animals caused a decrease in the average tumor pO2 from 28.61 +/- 8.74 mm Hg to 20.81 +/- 7.54 mm Hg in untreated control animals breathing atmospheric oxygen. It also caused the tumor uptake of Cu-ATSM to increase by 35%. Conversely, in animals breathing 100% oxygen, the average tumor pO2 increased to 45.88 +/-15.9 mm Hg, and the tumor uptake of Cu-ATSM decreased to 48% of that of the control animals. PET of animals treated in a similar fashion yielded time-activity curves showing significantly higher retention of the tracer in hypoxic tissues than in oxygenated tissues. CONCLUSION: These data confirm that Cu-ATSM uptake in tissues in vivo is dependent on the tissue pO2, and that significantly greater uptake and retention occur in hypoxic tumor tissue. Therefore, the possible use of Cu-ATSM PET as a prognostic indicator in the management of cancer is further validated.     

Is adrenal venous sampling necessary in all patients with hyperaldosteronism before adrenalectomy?

PURPOSE: To evaluate whether selective rather than universal use of adrenal vein sampling (AVS) may be warranted in patients with hyperaldosteronism to characterize and lateralize disease before adrenalectomy. MATERIALS AND METHODS: Fifty-nine consecutive patients with biochemically diagnosed hyperaldosteronism underwent unilateral adrenalectomy at a single center during a 10-year period. In one group (n = 30), adrenalectomy was based on computed tomography (CT) only; in another (n = 29), it was based on CT and AVS. The indication for AVS was equivocal CT finding (n = 26) or patient request (n = 3). Outcome variables were postoperative serum potassium and aldosterone levels, number of hypertensive medications, and mean arterial blood pressure at 6 months. RESULTS: Preoperatively, both groups were matched for age, years of hypertension, mean arterial blood pressure, and number of hypertensive medications. Average tumor sizes were 2 cm (range, 1-3 cm) in the CT-only group and 1 cm (range, 0-2.5 cm) in the CT/AVS group. Unilateral tumor was identified on CT in 30 patients (100%) in the CT-only group and in 17 patients (59%) in the CT/AVS group (P < .05). Postoperatively, aldosterone levels were lower in the CT-only group (6.3 ng/dL +/- 5.9 vs 13.5 ng/dL +/- 16; P < .05). Both groups had similar improvements in mean arterial blood pressure at 6 months (92 mm Hg +/- 12 vs 96 mm Hg +/- 9; P = .14), reductions in number of hypertensive medications (to 1.1 +/- 1.3 vs 1.2 +/- 1.1; P = .4), and improvements in hypokalemia (3.8 mEq/L +/- 0.5 vs 3.8 mEq/L +/- 0.5; P = .5). CONCLUSIONS: The clinical impact of adrenalectomy was similar in both groups. CT can be used to reliably diagnose adenomas larger than 1.0 cm. AVS should be used when CT findings are equivocal or both adrenal glands are abnormal.