Determination of the absolute intensity of the 1205 keV γ-ray emission from 91Y.

A radiochemically pure solution of 91Y was produced by the thermal neutron fission of 235U followed by successive chemical separations to remove fission product impurities. The gamma emission rate of the 91Y 1205 keV gamma was measured using multiple high purity germanium gamma spectrometers previously calibrated for counting efficiency using a certificated mixed nuclide gamma standard. The activity concentration of the 91Y was subsequently standardised by liquid scintillation counting. From the combination the activity concentration and gamma emission intensity, the absolute intensity of the 1205 keV gamma emission was derived as 0.2297(39)%. This data agrees within the quoted uncertainties with the absolute intensity of 0.26(4)% published in nuclear data sheets A=91 (Baglin, 2013), but reduces the uncertainty by an order of magnitude.

Local abnormalities in coagulation and fibrinolytic pathways predispose to alveolar fibrin deposition in the adult respiratory distress syndrome.

To determine the possible mechanism(s) promoting alveolar fibrin deposition in the adult respiratory distress syndrome (ARDS), we investigated the initiation and regulation of both fibrinolysis and coagulation from patients with ARDS (n = 14), at risk for ARDS (n = 5), and with interstitial lung diseases (ILD) (n = 8), and normal healthy individuals (n = 13). Bronchoalveolar lavage (BAL) extrinsic pathway inhibitor activity was increased in ARDS BAL compared with patients at risk for ARDS (P = 0.0146) or normal controls (P = 0.0013) but tissue factor-factor VII procoagulant activity was significantly increased in ARDS BAL compared with all other groups (P less than 0.001). Fibrinolytic activity was not detectable in BAL of 10 of the 14 patients with ARDS and low levels of activity were found in BAL of the other four ARDS patients. Depressed fibrinolysis in ARDS BAL was not due to local insufficiency of plasminogen; rather, there was inhibition of both plasmin and plasminogen activator. Plasminogen activator inhibitor 1 was variably detected and low levels of plasminogen activator inhibitor 2 were found in two ARDS BAL samples, but plasminogen activator inhibitor 2 was otherwise undetectable. ARDS BAL antiplasmin activity was, in part, due to alpha 2-antiplasmin. We conclude that abnormalities that result in enhanced coagulation and depressed fibrinolysis, thereby predisposing to alveolar fibrin deposition, occur in the alveolar lining fluids from patients with ARDS.

Pretreatment, prediagnosis immunoglobulin, and alpha 1-antitrypsin levels in patients with bronchial carcinoma.

Sera from 148 patients suspected of having bronchial carcinoma were evaluated for concentrations of IgA, IgM, IgG, and alpha 1-antitrypsin (alpha 1-AT). Histologically, 137 tumor specimens obtained by bronchoscopy or surgical biopsy were diagnosed as squamous cell carcinoma (55%), adenocarcinoma (18%), undifferentiated small cell carcinoma (20%), or undifferentiated large cell carcinoma (7%). The tumor types of the remaining 11 patients were not identifiable from the records but were included as a separate group. Serum protein values were compared with those of a control group of 60 healthy adult volunteers. Regression analysis of age, race, and sex effects on the results of comparisons between test and control groups indicated that, with the possible exception of age and IgM, these three independent variables did not significantly influence the observations. Both serum IgA and alpha 1-AT were significantly elevated in all tumor groups when compared to the control levels. This was not the situation for serum IgG. Results for serum IgM were equivocal and depended on the statistical methods used. Although the serum immunoglobulin concentrations for the small cell carcinoma group were consistently lower than those for the other tumor cell types, no statistically significant difference existed between the five tumor groups in this regard.

Protein classification artificial neural system.

A neural network classification method is developed as an alternative approach to the large database search/organization problem. The system, termed Protein Classification Artificial Neural System (ProCANS), has been implemented on a Cray supercomputer for rapid superfamily classification of unknown proteins based on the information content of the neural interconnections. The system employs an n-gram hashing function that is similar to the k-tuple method for sequence encoding. A collection of modular back-propagation networks is used to store the large amount of sequence patterns. The system has been trained and tested with the first 2,148 of the 8,309 entries of the annotated Protein Identification Resource protein sequence database (release 29). The entries included the electron transfer proteins and the six enzyme groups (oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases), with a total of 620 superfamilies. After a total training time of seven Cray central processing unit (CPU) hours, the system has reached a predictive accuracy of 90%. The classification is fast (i.e., 0.1 Cray CPU second per sequence), as it only involves a forward-feeding through the networks. The classification time on a full-scale system embedded with all known superfamilies is estimated to be within 1 CPU second. Although the training time will grow linearly with the number of entries, the classification time is expected to remain low even if there is a 10-100-fold increase of sequence entries. The neural database, which consists of a set of weight matrices of the networks, together with the ProCANS software, can be ported to other computers and made available to the genome community. The rapid and accurate superfamily classification would be valuable to the organization of protein sequence databases and to the gene recognition in large sequencing projects.

Beta-Carotene, vitamin A, and lung cancer chemoprevention: results of an intermediate endpoint study.

A randomized, placebo-controlled clinical trial of beta-carotene and retinol was conducted with 755 former asbestos workers as study subjects. The targeted endpoint for the intervention study was a reduction in the incidence and prevalence of sputum atypia. The dosage of 50 mg beta-carotene/d and 25,000 IU retinol/d on alternate days resulted significant increases in serum concentrations of both agents with no clinically significant toxicity. Skin yellowing was observed in approximately 35% of patients and may have contributed adversely to protocol adherence. Baseline analysis revealed that smoking and drinking were associated with lower concentrations of serum beta-carotene, even after dietary carotene intake was adjusted for (P < 0.0001). Baseline concentrations of retinol were apparently lowered by smoking (P < 0.002) and increased by drinking (P < 0.0001). Drinking and smoking also were significantly related to lower beta-carotene concentrations after supplementation (P < 0.001). No significant reduction in sputum atypia was observed after treatment.

Lupus lung.

The morphologic findings from 18 autopsy lungs of systemic lupus erythematosus were studied. Each case revealed varying degrees of pleuropulmonary disease. A universal feature was visceral pleural thickening, while findings present in more than one half of the cases included pulmonary congestion (17/18) and edema (15/18), pleural adhesions (11/18) and pleural effusions (10/18) and intraalveolar hemorrhage (10/18). Also seen were bronchopneumonia (9/18), interstitial fibrosis (6/18), cytomegalovirus infection (3/18), interstitial pneumonitis (2/18), hyaline membranes (2/18), and acute vasculitis (1/18) and pleuritis (1/18). These results, together with those of previously reported studies of lupus lung, establish that although certain characteristic pleuropulmonary disease processes are frequently found at autopsy, none is a highly specific marker for the disease.

Platelet-specific alpha-granule proteins and thrombospondin in bronchoalveolar lavage in the adult respiratory distress syndrome.

Levels of platelet-specific alpha-granule proteins, PF, BTG, and TSP were measured in BAL fluids of patients with the ARDS, ILD, and normal healthy subjects, comprising two separate cohorts. In both groups BAL showed elevated levels of BTG and thrombospondin in ARDS patients. Low levels of PF4 were found in BAL and did not differ between ARDS and control patients. The BTG:PF4 ratio was 2:1 or greater in BAL of ARDS patients and of control subjects with other lung diseases, suggesting in vivo release. In ARDS patients, the ratio of TSP to BTG exceeded that usually found in plasma. In ARDS patients in group 2, BAL levels of TSP, BTG, and total protein correlated strongly with the composite injury scores that were used to quantitate their degree of lung injury. Elevated levels of platelet-derived proteins, which modulate chemotaxis of inflammatory cells and promote connective tissue reorganization, occur in the alveolar compartment of ARDS and ILD patients but are usually undetectable in BAL of healthy control subjects. Levels in these patients in BAL fluid are nonspecific indices of the severity of lung injury in patients with ARDS.

Initial clinical assessment of the comatose patient: cerebral malaria vs. meningitis.

One hundred twenty-one Liberian children were admitted in coma to the ELWA Hospital, Monrovia, Liberia. Admitting diagnoses, before lumbar puncture, were compared with discharge diagnoses. Ninety-four children were discharged with a final diagnosis of cerebral malaria and 27 with a diagnosis of meningitis. The admitting diagnosis was correct in 76.6% (72 of 94) of patients with cerebral malaria and 59.3% (16 of 27) of patients with meningitis. The cerebrospinal fluid leukocyte count was the single most significant factor in determining the correct diagnosis. Without the cerebrospinal fluid analysis, the discriminant accuracy (77%), i.e. definitive separation of the two illnesses, was comparable to the physician's admission diagnosis (73%). Other data contributing to the differential diagnosis of cerebral malaria and meningitis included the number of days of fever before admission, the presence or absence of nuchal rigidity, fontanelle fullness and peripheral blood malaria smear. Mortality rates for cerebral malaria and meningitis were 14.9 and 29.6%, respectively. These data suggest that physicians cannot reliably discriminate between cerebral malaria and meningitis without cerebrospinal fluid analysis.

Effects of lung volume on clearance of solutes from the air spaces of lungs.

Several investigators have shown that the clearance rate of aerosolized 99mTc-labeled diethylenetriamine pentaacetate (DTPA, mol wt = 492, radius = 0.6 nm) from the air spaces of the lungs of humans and experimental animals increases with lung volume. To further investigate this phenomenon we performed a compartmental analysis of the 2-h clearance of DTPA from the lungs of anesthetized sheep using a new method to more accurately correct for the effects of DTPA recirculation. This analysis showed that the DTPA clearance in eight sheep ventilated with zero end-expired pressure was best described by a one-compartment model with a clearance rate of 0.42 +/- 0.15%/min. Ventilating eight sheep with an end-expired pressure of 10 cmH2O throughout the study increased the end-expired volume 0.4 +/- 0.1 liter BTPS and created a clearance curve that was best described by a two-compartment model. In these sheep 56 +/- 16% of the DTPA cleared from the lungs at a rate of 7.9 +/- 2.9%/min. The remainder cleared at a rate similar to that measured in the sheep ventilated with zero end-expired pressure (0.35 +/- 0.18%/min). Additional control and lung inflation experiments were performed using 99mTc-labeled human serum albumin (mol wt = 66,000, radius = 3.6 nm). In six control sheep ventilated with zero end-expired pressure the albumin clearance was best described by a one-compartment model with a clearance rate of 0.06 +/- 0.02%/min. The clearance rate in six sheep with increased lung volume was slightly larger (0.09 +/- 0.02, P less than 0.05) but was well described by a one-compartment model.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of three tracers for detecting lung epithelial injury in anesthetized sheep.

We compared the ability of three aerosolized tracers to discriminate among control, lung inflation with a positive end expired pressure of 10 cmH2O, lung vascular hypertension and edema without lung injury, and lung edema with lung injury due to intravenous oleic acid. The tracers were 99mTc-diethylenetriaminepentaacetate (99mTc-DTPA, mol wt 492), 99mTc-human serum albumin (99mTc-ALB, mol wt 69,000), and 99mTc-aggregated albumin (99mTc-AGG ALB, mol wt 383,000). 99mTc-DTPA clearance measurements were not able to discriminate lung injury from lung inflation. The 99mTc-AGG ALB clearance rate was unchanged by lung inflation and increased slightly with lung injury. The 99mTc-ALB clearance rate (0.06 +/- 0.02%/min) was unchanged by lung inflation (0.09 +/- 0.02%/min, P greater than 0.05) or 4 h of hypertension without injury (0.09 +/- 0.04%/min, P greater than 0.05). Deposition of 99mTc-ALB within 15 min of the administration of the oleic acid increased the clearance rate to 0.19 +/- 0.06%/min, which correlated well with the postmortem lung water volume (r = 0.92, P less than 0.01). This did not occur when there was a 60-min delay in the deposition of 99mTc-ALB. We conclude that 99mTc-ALB is the best indicator for studying the effects of lung epithelial injury on protein and fluid transport into and out of the air spaces of the lungs in a minimally invasive manner.

A potentially expanded role for enoxaparin in preventing venous thromboembolism in high risk blunt trauma patients.

BACKGROUND: Venous thromboembolism (VTE) is a frequent and potentially life-threatening complication after trauma. The purpose of this study is to investigate the effectiveness of enoxaparin in preventing deep venous thrombosis (DVT) and pulmonary embolism (PE) after injury in patients who are at high risk for developing VTE. STUDY DESIGN: A prospective single-cohort observational study was initiated for seriously injured blunt trauma patients admitted to a Level I trauma center during a 7-month period. Patients were eligible for the study if time hospitalized was > or = 72 hours, Injury Severity Score (ISS) was > or = 9, enoxaparin was started within 24 hours after admission, and one or more of the following high risk criteria were met: age > 50 years, ISS > or = 16, presence of a femoral vein catheter, Abbreviated Injury Score (AIS) > or = 3 for any body region, Glasgow Coma Scale (GCS) Score < or = 8, presence of major pelvic, femur, or tibia fracture, and presence of direct blunt mechanism venous injury. Patients with closed head injuries and nonoperatively treated solid abdominal organ injuries were also potential participants. The primary outcomes measured were thromboembolic events--either a documented lower extremity DVT by duplex color-flow doppler ultrasonography or a PE documented by rapid infusion CT pulmonary angiography or conventional pulmonary angiography. RESULTS: There were 118 patients enrolled in the study. Two patients (2%) developed DVT, one of which was proximal to the calf (95% confidence interval, 0% to 6%). Two of 12 patients (17%) with splenic injuries who received enoxaparin failed initial nonoperative management. There were no other bleeding complications, and no clinical evidence or documented episodes of PE. One patient died from multiple system organ failure. CONCLUSIONS: Enoxaparin is a practical and effective method for reducing the incidence of VTE in high risk, seriously injured patients. This study supports further investigation into the safety of enoxaparin prophylaxis in patients with closed head injuries and nonoperatively treated solid abdominal organ injuries.

The high morbidity of blunt cerebrovascular injury in an unscreened population: more evidence of the need for mandatory screening protocols.

BACKGROUND: Blunt cerebrovascular injuries are rare injuries causing substantial morbidity and mortality. The appropriate screening methods and treatment options for these injuries are controversial. We examined our experience with these injuries at a community Level I Trauma center over a 51 month period. STUDY DESIGN: A retrospective review and analysis was done of all patients with the diagnosis of a blunt cerebrovascular injury during this period. RESULTS: Fourteen patients had blunt carotid injury (0.40%) and three had blunt vertebral injury (0.09%) out of 3,480 total blunt admissions. The overall incidence of blunt cerebrovascular injury was 0.49%. The most common associated injuries were to the head (59%) and chest (47%) regions. The overall mortality rate was 59% (10 of 17), with death occurring in 8 of 14 (57%) blunt carotid injury patients and 2 of 3 (67%) blunt vertebral injury patients. Eight of ten (80%) deaths were directly attributable to the blunt cerebrovascular injury. Median time until diagnosis was 12.5 h (range 1-336 h) for the entire group and 19.5 h for nonsurvivors. Diagnosis was delayed > 24h in 7 patients and > 48h in 5 patients. All five patients whose diagnoses were delayed > 48 h developed complications, and four (80%) of these patients died. CONCLUSIONS: Blunt cerebrovascular injury is uncommon, but lethal; particularly when the diagnosis is delayed. Aggressive screening protocols based on mechanism of injury, associated injuries, and physical findings are justified to minimize morbidity and mortality. Head and chest injuries may serve as markers for blunt cerebrovascular injury. Most deaths are directly attributable to the blunt cerebrovascular injury and not to associated injuries.

The value of medical history and physical examination in diagnosing sacroiliac joint pain.

STUDY DESIGN: This prospective study evaluated the diagnostic utility of historically accepted sacroiliac joint tests. A multidisciplinary expert panel recommended 12 of the "best" sacroiliac joint tests to be evaluated against a criterion standard of unequivocal gain relief after an intra-articular injection of local anesthetic into the sacroiliac joint. OBJECTIVES: To identify a single sacroiliac joint test or ensemble of test that are sufficiently useful in diagnosing sacroiliac joint disorders to be clinically valuable. SUMMARY OF BACKGROUND DATA: No previous research has been done to evaluate any physical test of sacroiliac joint pain against an accepted criterion standard. METHODS: Historical data was obtained, and the 12 tests were performed by two examiners on 85 patients who subsequently underwent sacroiliac joint blocks. Ninety percent or more relief was considered a positive response, and less then 90% relief was considered a negative response. RESULTS: There were 45 positive and 40 negative responses. No historical feature, none of the 12 sacroiliac joint tests, and no ensemble of these 12 tests demonstrated worthwhile diagnostic value. CONCLUSION: Sacroiliac joint pain is resistant to identification by the historical and physical examination data from tests evaluated in this study.

Efficacy and validity of radiofrequency neurotomy for chronic lumbar zygapophysial joint pain.

STUDY DESIGN: A prospective audit. OBJECTIVE: To establish the efficacy of lumbar medial branch neurotomy under optimum conditions. SUMMARY OF BACKGROUND DATA: Previous reports of the efficacy of lumbar medial branch neurotomy have been confounded by poor patient selection, inaccurate surgical technique, and inadequate assessment of outcome. METHODS: Fifteen patients with chronic low back pain whose pain was relieved by controlled, diagnostic medial branch blocks of the lumbar zygapophysial joints, underwent lumbar medial branch neurotomy. Before surgery, all were evaluated by visual analog scale and a variety of validated measures of pain, disability, and treatment satisfaction. Electromyography of the multifidus muscle was performed before and after surgery to ensure accuracy of the neurotomy. All outcome measures were repeated at 6 weeks, and 3, 6, and 12 months after surgery. RESULTS: Some 60% of the patients obtained at least 90% relief of pain at 12 months, and 87% obtained at least 60% relief. Relief was associated with denervation of the multifidus in those segments in which the medial branches had been coagulated. Prelesion electrical stimulation of the medial branch nerve with measurement of impedance was not associated with outcome. CONCLUSIONS: Lumbar medial branch neurotomy is an effective means of reducing pain in patients carefully selected on the basis of controlled diagnostic blocks. Adequate coagulation of the target nerves can be achieved by carefully placing the electrode in correct position as judged radiologically. Electrical stimulation before lesioning is superfluous in assuring correct placement of the electrode.

Factors relating to recurrence of chronic pulmonary histoplasmosis following treatment with amphotericin B.

A retrospective analysis was made of cases of Chronic Pulmonary Histoplasmosis during the admission in which patients received amphotericin B to determine if there were features related to recurrence of the disease. There was significance at the p less than or equal to 0.05 level in that the nonrecurrent cases tended to have a lower initial complement fixation titers using mycelial antigen; had initial complement fixation tests which were likely to result in no reaction using either mycelial or yeast antigen; and had more rapid drops in the complement fixation values using the yeast antigen. Although the present evaluation does not suggest an absolute minimum effective dose of amphotericin B, it would seem plausible to administer a course of at least 2300 mg if the initial complement fixation test was nonreactive but if the drug was tolerated well by the patient and the initial complement fixation test was reactive, the goal should be at least 2500 mg.

Changing utilization of cytopathology versus histopathology in the diagnosis of lung cancer.

We studied the utilization rates of 1) cytopathology procedures [sputum, fine-needle aspirates (FNA), bronchial washings and brushings] versus 2) histopathology procedures (bronchial biopsies, lymph node biopsies, lobectomies, pneumonectomies) in the diagnosis of lung cancer, over two time periods (1967/1987). Comparisons were made in the utilization rates of these two diagnostic procedures in two groups of 100 patients each. Statistically significant changes included 1) an increase of cytopathology procedures, as the sole means of diagnosis; 2) an increase in FNAs; 3) an increased percentage of positive cytopathologic diagnosis; and 4) a decrease of major surgical procedures (lobectomy, pneumonectomy), as means of initial pathologic diagnosis. This study provides data supporting the trend of decreasing surgical procedures for initial diagnosis of lung cancer, with greater, more effective utilization of cytopathologic (particularly FNA) procedures.

Conventional respiratory cytology versus fine needle aspiration cytology in the diagnosis of lung cancer.

The results of 184 fine needle aspiration (FNA) cytologic examinations were compared with the findings of "conventional" respiratory cytology (on sputums, bronchial brushings and bronchial washings) and histology (on biopsy and autopsy samples) and with the medical records. Positive cytologic results were obtained in 6 (10%) of 60 sputums, 17 (21%) of 80 brushings, 16 (19%) of 84 washings and 82 (44%) of 184 aspirates. These positive results were confirmed by biopsy for 6 of 6 sputums, 16 of 17 brushings and 15 of 16 washings. Among the 82 patients with a positive FNA cytology, malignancy was confirmed by lung biopsy in 39 and by autopsy in 2; the cytologic diagnosis was supported by clinical and radiographic findings in all but 1 of the remaining 41 patients. Using transbronchial lung biopsy, autopsy and medical records as final standards, the positive predictive values were 100% for sputum, 94.1% for brushings, 93.0% for washings and 98.6% for FNA samples. The high positive predictive values of FNA and the other cytologic procedures indicate that these diagnostic modalities provide simple, rapid and reliable methods for the diagnosis of lung cancer.

Statistical comparison of aerosol-induced and spontaneous sputum specimens in the Tyler Asbestos Workers Program.

More than 10,000 sputum specimens, including both aerosol-induced and three-day pooled spontaneous specimens, were processed within a five-year period from a surveillance program of a cohort of 858 former asbestos workers and 188 controls. During the first two years, slides were prepared by the "pick and smear" method; thereafter, the Saccomanno technique was used. Each specimen was examined for both the degree of cellular atypia and the number of ferruginous bodies. Data analysis revealed that the number of ferruginous bodies in the spontaneous specimens showed a higher correlation with chest X rays and pulmonary function tests than did those in aerosol-induced specimens. Consequently, a study was undertaken to compare the results of all aerosol-induced and spontaneous cough specimens prepared by the pick and smear and Saccomanno methods. Matched pairs of specimens from the same individuals were also compared. More specimens with atypias were obtained from the spontaneous sputa using the Saccomanno technique. More ferruginous bodies were found in the aerosol-induced specimens using the pick and smear method. The pick and smear method was more effective for detecting ferruginous bodies in both induced and spontaneous specimens.

Diagnosis and typing of lung carcinomas by cytopathologic methods. A review of 108 cases.

A correlative review was made of the type of cytology specimens (sputum, bronchial washing and bronchial brushing) together with the corresponding histopathologic specimens of 108 patients. One hundred patients had primary pulmonary carcinomas diagnosed histopathologically (84) or clinically (16); 5 had carcinomas metastatic to the lungs and 3 had apparently false-positive cytologic results for lung cancer. The correlative review was used to determine the diagnostic reliability of pulmonary cytopathologic techniques in the detection and classification of lung carcinomas (i.e., the sensitivity and accuracy). The overall sensitivities of sputum, bronchial washing and bronchial brushing cytology were 60%, 66% and 77%, respectively (p less than 0.05). Bronchial brushing had a higher sensitivity (80%) for peripheral and metastatic lesions than did sputum (37%) or bronchial washing (60%). The overall accuracies of sputum, bronchial washing and bronchial brushing cytology were 79%, 75% and 76%, respectively, which is not statistically different. Regardless of the sampling methods, cytologic typing of squamous-cell and small-cell carcinomas was highly accurate but was less satisfactory for the other types of lung carcinomas. In the 16 cases in which endoscopic biopsies were either not attempted or gave negative results, one or more pulmonary cytologic specimens showed malignant cells. It is concluded that: (1) pulmonary cytopathologic techniques have excellent sensitivity and accuracy in the diagnosis of lung carcinomas; (2) they may establish the diagnosis of pulmonary carcinomas when endoscopic biopsies give negative results; and (3) they are particularly helpful in cases in which endoscopic biopsies suffer from a low yield (peripheral lesions) or create a considerable danger to the patients (iatrogenic hemorrhage).

Asbestos bodies and particulate matter in sputum from former asbestos workers. An ultrastructural study.

From sputum samples collected from nine former asbestos workers, one portion not needed for cytopathologic screening was fixed, embedded and sectioned for transmission electron microscopy (TEM) while a second portion was digested and collected on a Nuclepore filter for scanning electron microscopy (SEM). Energy-dispersion analysis was used in assessing inorganic matter in both preparations. The ultrastructural relationships between the ferruginous bodies and related macrophages as well as the presence of other particulate matter in the preparations were studied. Our results are the first to confirm the presence of uncoated asbestos fibers, diatomaceous earth and aluminosilicates in sputum. Our data indicate that it would be reasonable to use this analytical technique as an initial test before using invasive procedures in the diagnosis of many pneumoconioses and other lung diseases.