Serial Observations after High Dose Talc Slurry in the Rabbit Model for Pleurodesis

The mechanisms leading to a pleurodesis after the intrapleural injection of a sclerosing agent are not completely understood. The purpose of the present study was to make serial observations over 28 days on the pleural fluid findings and the gross and microscopic changes in the pleura after talc slurry administered intrapleurally at a high dose. Sixty-six rabbits received 400 mg/kg talc slurry. Ten to 12 rabbits were sacrificed 1, 2, 4, 7, 14, and 28 days after the intrapleural injection. At sacrifice the pleural fluid was measured and analyzed, and the pleural surfaces were studied grossly and microscopically. The intrapleural injection of 400 mg/kg talc slurry resulted in an acute exudative pleural effusion that persisted for 4 days. There was a progressive increase in the gross and microscopic fibrosis over the 28 days. Talc was present at the time of sacrifice in all animals. At 28 days there was a clinically significant pleurodesis in all rabbits; pleurodesis was not observed before this time. From this study we conclude that the intrapleural injection of 400 mg/kg talc slurry leads to an acute exudative pleural effusion and clinically significant pleurodesis that is present on day 28 but not day 14. It appears that the production of a pleurodesis requires higher doses of talc in rabbits without a chest tube than in humans with a chest tube. Accepted for publication: 11 December 1997     

Hemoglobin synthesis in individual bursts from normal adult blood: all bursts and subcolonies synthesize G gamma-and A gamma-globin chains

Gamma-globin chain synthesis has been evaluated in individual bursts and subcolonies that were generated by normal adult blood BFU-Es in methylcellulose cultures containing semipurified erythropoietin (Ep) and then analyzed via either isoelectric focusing (IEF) of globin chains or immunofluorescence techniques. At variance with previously reported results, based on plasma clot culture and immunofluorescence, all bursts and subcolonies analyzed synthesize gamma-globin chains. Identification of gamma-chains has been confirmed by preparative IEF of HbF, followed by either carboxymethylcellulose chromatography or IEF analysis of the resulting globin chains. In all bursts analyzed, the relative synthesis of the two types of gamma-globin chains (G gamma and A gamma) shows an adult ratio (i.e., approximately 1:1). The results obtained via IEF have been confirmed by immunofluorescence studies, which apparently showed presence of at least some HbF-positive cells within all scrutinized bursts or subcolonies. The significance of these studies is discussed in the light of current hypotheses on mechanism(s) underlying HbF synthesis in normal adults.     

Cleavage and activation of human factor IX by serine proteases

Human factor IX circulates as a single-chain glycoprotein. Upon activation in vitro, it is cleaved into disulfide-linked light and heavy chains and an activation peptide. After reduction of activated 125I-factor IX, the heavy and light chains are readily identified by gel electrophoresis. A direct, immunoradiometric assay for factor IXa was developed to assess activation of factor IX for proteases that cleaved it. The assay utilized radiolabeled antithrombin III with heparin to identify the active site and antibodies to distinguish factor IX. After cleavage of factor IX by factor XIa, factor VIIa- tissue thromboplastin complex, or the factor X-activating enzyme from Russell's viper venom, antithrombin III bound readily to factor IXa. Cleavage of 125I-factor IX by trypsin, chymotrypsin, and granulocyte elastase in the presence of calcium yielded major polypeptide fragments of the sizes of the factor XIa-generated light and heavy chains. Kallikrein did not cleave the zymogen. Nonactivation cleavage was noted by thrombin, but only in the absence of calcium. When the immunoradiometric assay was used to assess trypsin-cleaved factor IX, the product bound antithrombin III, but not maximally. After digesting with insolubilized trypsin, clotting activity confirmed activation. In contrast, incubation of factor IX with elastase (Takaki A et al, J Clin Invest 71:1706, 1983) or chymotrypsin did not lead to generation of an antithrombin III-binding site, despite their digestion of 125I-factor IX into heavy and light chain-sized fragments. In evaluating activation of factor IX, physical evidence of activation cleavages does not necessarily correlate with generation of an active site.     

Pressure-time product during continuous positive airway pressure, pressure support ventilation, and T-piece during weaning from mechanical ventilation

The objective of this study was to compare the effects of continuous positive airway pressure (CPAP), pressure support ventilation (PS), and T-piece on the pressure-time product (PTP) during weaning from mechanical ventilation. The PTP is an estimate of the metabolic work or oxygen consumption of the respiratory muscles. We studied 10 intubated patients recovering from acute respiratory failure of various etiologies. A modified continuous flow (flow-by) CPAP of 0 and 5 cm H2O (CPAP-0 and CPAP-5, respectively), PS of 5 cm H2O (PS-5), and T-piece were applied in random order for 30 min each. In the last 5 min of the 30-min periods, we measured the esophageal pressure and transdiaphragmatic pressure-time products--PTP(es) and PTP(di), cm H2O.s/min, respectively-multiplied by respiratory frequency. Breathing pattern, total lung resistance (RL), quasi-static lung compliance (CL), intrinsic positive end-expiratory pressure (PEEPi), end-expiratory transpulmonary pressure (Ptpexp), arterial blood gases, blood pressure, and heart rate were also measured. In comparison to T-piece, CPAP-5 decreased PTP(es) 40% (p less than 0.01) and PTP(di) 43% (p less than 0.02), whereas PS-5 decreased PTP(es) 34% (p less than 0.01) and PTP(di) 38% (p less than 0.05). The decrease in PTP(es) with CPAP-5 was associated with a significant reduction in RL, and to a less extent in PEEPi relative to airway pressure. The contribution of the decrease in PEEPi to the reduction in PTP(es) amounted to 36%. With PS-5, respiratory system mechanics and PEEPi were not significantly different compared with T-piece. With CPAP-0, PTP tended to be lower than with T-piece.(ABSTRACT TRUNCATED AT 250 WORDS)     

Etiology and prognostic significance of massive pleural effusions

It has been stated that malignancy is the most common aetiology of massive pleural effusions. To determine the most frequent causes of massive pleural effusions and to assess the diagnostic yield of different diagnostic procedures and survival, we prospectively studied 1084 patients with pleural effusion. Massive pleural effusions were identified in 121 of 1084 patients (11.2%). Compared with non-massive pleural effusions, massive pleural effusions were significantly more likely to be malignant (53.7% vs. 38.3%, P=0.03) or secondary to cirrhosis (9.9% vs. 2.6%, P=0.0000). On the other hand, massive pleural effusions were significantly less likely to be secondary to infection (10.7% vs. 19.2%, P=0.003) or congestive heart failure (0.8% vs. 6.7%, P=0.03). There was a significant increase in the yield of diagnostic studies in patients with massive malignant pleural effusions (56.9% for cytological studies and 36.9% for biopsies). On the other hand, there was no difference in the diagnostic yield of microbiological and histological studies in the group of tuberculous pleural effusions. In our study population, patients with non-massive malignant pleural effusions had a significantly better survival than those with massive malignant pleural effusions, with a median survival of 8 months (95% confidence interval, 7-9) compared with 5 months (95% confidence interval, 4-6) (P=0.0009). We conclude that malignancy is the most common cause of a massive exudative effusion. Massive malignant pleural effusions are associated with worse survival, independent of age and histologic subgroup, than are non-massive malignant pleural effusions.     

Working-memory capacity, age, and memory for discourse

Two experiments explored the issue of whether age-related differences in memory for discourse can be explained by age-related differences in working memory capacity. Young and older adults were given a series of tasks designed to measure working memory capacity and memory for paragraphs. Although age-related differences were observed on digit, word, and sentence spans as well as on recall (Experiment 1) and recognition (Experiment 2), retention was not predicted well by scores on any of the span measures for either young or older adults in either experiment. The implications of these findings for hypotheses that age-related declines in working memory are responsible for problems in memory for prose are considered.     

Comparison of the effects of labetalol and hydrochlorothiazide on the ventilatory function of hypertensive patients with asthma and propranolol sensitivity

Previous studies have shown that labetalol, a new alpha- and beta-adrenergic antagonist, is relatively safe for the treatment of hypertension in patients with chronic obstructive pulmonary disease (COPD). This multicenter study was designed to evaluate its effects in hypertensive patients with asthma and propranolol sensitivity. Hypertension was successfully controlled in 18 of 21 patients who received labetalol in increasing doses, up to 1,200 mg/day. The decrease in mean FEV1 (1.5 percent) two hours after the highest dose of labetalol was not statistically significant, although there was a gradual decline in mean baseline FEV1 during the four-week treatment period. Antihypertensive agents other than adrenergic antagonists should be considered for the management of hypertension in patients with asthma, especially those with marked reversibility of airflow. If treatment with beta-adrenergic antagonists is indicated, labetalol is recommended over other currently available agents.     

Exposure of Rats to Ethanol from Postnatal Days 4 to 8: Alterations of Cholinergic Neurochemistry in the Cerebral Cortex and Corpus Striatum at Day 20

Male and female rat pups were administered ethanol (3 g/kg/dose) twice daily by intragastric intubation between postnatal Day (PN) 4 and 8. Pups were maternally reared throughout the exposure period and until sacrifice on PN20. The consequences of this growth spurt exposure to ethanol were measured by an impact upon body growth, as well as upon specific growth parameters and cholinergic neurochemical factors within the cerebral cortex and corpus striatum. Specific endpoints included muscarinic receptor binding dynamics, acetylcholinesterase (AChE) and choline acetyltransferase (CAT) activities, regional wet weights, and subcellular protein content. In male pups, ethanol resulted in a significant enhancement of body weight gain and an increase in striatal but not cortical mass. Additionally, ethanol exposure resulted in a significant increase in striatal muscarinic receptor affinity, regardless of gender. This was accompanied by evidence of a significantly greater density of striatal muscarinic receptors in males versus females, regardless of treatment. Overall, the ethanol-associated effects are suggestive of a drug-induced developmental delay. Gender-specific, treatment-independent differences were also detected in the developing brain regions. Thus, regardless of treatment, cerebral cortical S1-level protein content was found to be significantly greater in males than in females. Furthermore, there were gender-based, significant differences in AChE activity within the striatum of control pups (males greater than females). Ethanol exposure resulted in a loss of this gender-based difference. We conclude that the cholinergic neurochemical development occurring in the striatum of the female rat brain between PN4 and 8 is exquisitely sensitive to ethanol-induced developmental delays which are not remediable by 12 subsequent days of maternal rearing in the absence of ethanol exposure.     

Transcutaneous aortovelography. A quantitative evaluation.

The haemotachograph is a non-invasive ultrasonic Doppler-shift instrument designed to measure the velocity of blood in the arch of the aorta by a technique referred to as transcutaneous aortovelography. Its accuracy has been assessed at cardiac catheterization in 20 patients. When transcutaneous aortovelographic values were compared with stroke volume determined by standard invasive techniques, a good proportional agreement was found. The accuracy of absolute flow values, as calculated from transcutaneous aortovelography and dimensional data, was, however, poor. Peak velocity determined from transcutaneous aortovelographic tracings agreed well with values obtained with a catheter tip electromagnetic velocity probe. Transcutaneous aortovelography is a useful non-invasive technique which can be used to determine phasic blood flow velocity in the aortic arch and to follow changes in cardiac output over a period of time.     

Patient with bilateral pleural effusion: are the findings the same in each fluid?

STUDY OBJECTIVES: To determine whether, in patients with bilateral pleural effusions, the main cellular and biochemical features of the pleural fluid on the right side differ from or correlate with those on the left side. We examined lactate dehydrogenase (LDH), glucose, and total protein (TP) levels, RBC count, nucleated cell count (NCC), and differential cell count. PATIENTS AND METHODS: Twenty-seven patients with bilateral pleural effusions, including 13 patients with effusions after coronary artery bypass graft surgery, 12 patients with congestive heart failure, 1 patient with malignant pericarditis, and 1 patient with renal failure, were studied retrospectively. RESULTS: The right-sided and the left-sided pleural effusions did not differ in the mean TP (p = 0.38), glucose (p = 0.31), and LDH (p = 0.39) levels, RBC count (p = 0.31), NCC (p = 0.96), and the percentage of neutrophils (p = 0.22), lymphocytes (p = 0.73), mononuclear cells (MNCs) [p = 0.49], and eosinophils (p = 0.65). The bias +/- precision was 0.1 +/- 0.64 g/dL for TP, - 2.7 +/- 23 mg/dL for glucose, 41 +/- 362 IU/L for LDH, 6,100 +/- 62,900 cells/ micro L for RBC count, - 36 +/- 1,043 cells/ micro L for NCC, - 2.9 +/- 11.6% for the percentage of neutrophils, 1.15 +/- 17% for the percentage of lymphocytes, 2.3 +/- 17% for the percentage of the MNCs, and - 0.15 +/- 5.4% for the percentage of eosinophils. Moreover, there was a close correlation between the right-sided and the left-sided pleural effusions concerning TP level (r = 0.85, p < 0.001), glucose level (r = 0.78, p < 0.001), LDH level (r = 0.71, p < 0.001), RBC count (r = 0.66, p < 0.001), NCC (r = 0.60, p = 0.001), and the percentage of neutrophils (r = 0.77, p < 0.001), lymphocytes (r = 0.77, p < 0.001), MNCs (r = 0.74, p < 0.001), and eosinophils (r = 0.84, p < 0.001). CONCLUSION: Since the pleural fluid findings tend to be similar in both sides of patients with bilateral pleural effusion, we suggest that diagnostic thoracentesis may not need to be performed on both sides, unless there is a specific clinical indication.