Search

Objective: To investigate the effect of information management of intravenous drugs on anemia in maintenance hemodialysis patients. Methods: The information management of intravenous drugs was a management system developed by the Hemodialysis Center of Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital in April 2020. The parameters six months before and after the use of the information management system were retrospectively collected and compared, including the rate of reaching the standard of hemoglobin, ferritin, transferrin saturation rate and the incidence of cardiovascular events. Specifically, the control stage was from October 2019 to March 2020, which was before the use of information management, and the study stage was from April to September 2020, which was after the use of information management. Results: There were 285 patients (190 males and 95 females) included in the control stage, with an average age of (62.4±13.2) years, while 278 patients (193 males and 85 females) were included in the study stage, with an average age of (62.8±13.2) years. Compared with the control stage, the rate of reaching the standard of hemoglobin [47.8% (797/1 668) vs 40.2% (687/1 710), P <0.001], ferritin [39.0% (217/556) vs 31.2% (178/570), P =0.006], and transferrin saturation [64.7% (360/556) vs 58.6% (334/570), P =0.034] increased in the study stage. The incidence of cardiovascular events in the study stage was 11.2% (31/278), which was significantly lower than that in the control stage [16.5% (47/285)] ( P =0.043). Conclusion: The information management of intravenous drugs in the hemodialysis center may help improve the anemia status in maintenance hemodialysis patients.

A female patient diagnosed with ankylosing spondylitis experienced a new onset acute iritis following the initiation of etanercept therapy and recurrent episodes of iritis continues during the treatment of etanercept. Etanercept-associated iritis was suspected. Anti-TNF therapies can alleviate uveitis in some studies, but in some other anecdotal reports etanercept is considered as the main cause of uveitis. A literature review is presented below. For clinicians, more attention must be paid to the potential association between uveitis or iritis and etanercept, and more careful surveillance of patients under etanercept treatment is necessary.

Acylsilanes with terminal alpha-stannyl bromide or xanthate functionalities are prepared. Alpha-stannyl radicals generated from these acylsilanes undergo intramolecular cyclizations to give cyclic silyl enol ethers regiospecifically. The radical processes involve radical cyclization, Brook rearrangement, and beta-fragmentation in sequence. A tributylstannyl group serves as the radical leaving group. The newly formed sigma-bond and pi-bond are located between the same two carbon atoms. This approach is limited to the formation of five-membered rings. In another route, omega-bromo-alpha-phenylsulfonylacylsilanes are synthesized. The radical cyclizations of these alpha-sulfonylacylsilanes also give cyclic silyl enol ethers. The phenylsulfonyl moiety is the radical leaving group in this system. Furthermore, the newly formed sigma-bond and pi-bond are located at adjacent positions sharing a single carbon atom. The latter approach is effective for both five- and six-membered ring formation.

Bcl-2 protein family members function either to promote or inhibit programmed cell death. Bcl-2, typically an inhibitor of apoptosis, has also been demonstrated to have pro-apoptotic activity (Cheng, E. H., Kirsch, D. G., Clem, R. J., et al. (1997) Science 278, 1966-1968). The pro-apoptotic activity has been attributed to the cleavage of Bcl-2 by caspase-3, which converts Bcl-2 to a pro-apoptotic molecule. Bcl-2 is a membrane protein that is localized in the endoplasmic reticulum (ER) membrane, the outer mitochondrial membrane, and the nuclear envelope. Here, we demonstrate that transient expression of Bcl-2 at levels comparable to those found in stably transfected cells induces apoptosis in human embryonic kidney 293 cells and in the human breast cell line MDA-MB-468 cells. Furthermore, we have targeted Bcl-2 specifically to either the ER or the outer mitochondrial membrane to test whether induction of apoptosis by Bcl-2 is dependent upon its localization within either of these membranes. Our findings indicate that Bcl-2 specifically targeted to the mitochondria induces cell death, whereas Bcl-2 that is targeted to the ER does not. The expression of Bcl-2 does result in its cleavage to a 20-kDa protein; however, mutation of the caspase-3 cleavage site (D34A) does not inhibit its ability to induce cell death. Additionally, we find that transiently expressed ER-targeted Bcl-2 inhibits cell death induced by Bax overexpression. In conclusion, the ability of Bcl-2 to promote apoptosis is associated with its localization at the mitochondria. Furthermore, the ability of ER-targeted Bcl-2 to protect against Bax-induced apoptosis suggests that the ER localization of Bcl-2 may play an important role in its protective function.

Rationale: Polydrug abuse is a problem that has been infrequently examined. In the present study, drug self-administration procedures were used to investigate the reinforcing effects of drug combinations., Objectives: To determine the absolute and relative response rates maintained by orally delivered methadone, cocaine, and their combinations under sequential and concurrent access. Choice between drug combinations containing different concentrations of cocaine was also determined., Methods: Oral intake of methadone, cocaine, and their combinations was studied with rhesus monkeys during daily 3-h sessions. Lip contact (the operant response) was reinforced by delivery of liquid contingent upon completion of a fixed-ratio schedule. In one series, the drugs and drug combinations were studied sequentially with the water vehicle concurrently available. In the next series, the drugs and drug combinations were concurrently available. In the third series, pairs of drug combinations containing different concentrations of cocaine were also concurrently available., Results: Methadone, cocaine and their combinations functioned as reinforcers. Under sequential access, response rates for the drug combinations and the component drugs were often similar. However, under concurrent access, response rates for the drug combinations were greater than response rates for the component drugs at the highest FR size for each condition. Also, drug combinations containing higher cocaine concentrations were preferred to combinations containing lower cocaine concentrations., Conclusions: Combinations of methadone and cocaine have relatively greater reinforcing effects than the component drugs, and these greater reinforcing effects are better detected with concurrent measures than with sequential measures.

Our new oropharyngeal intubation wedge made from a plastic 3-ml syringe has been used successfully for the expansion of the oropharyngeal cavity and visualization of vocal cords for endotracheal intubation in the rat. All the animals we used tolerated the intubation and ventilation procedures in a series of experiments. After the proper setting of the respirator, vital signs were maintained within normal range. The postmortem examination and measurements in the upper airway confirmed that the endotracheal tube was properly sited and also demonstrated the precise size of the device that should be used. The main advantages of this method include low cost, simplicity, and reliability. Furthermore, because no expensive, elaborate, difficult-to-operate, or hard-to-get special equipment is needed, this technique can be used in every laboratory.

Background: There is some evidence to suggest that laser exposure, when added to standard staple reduction techniques, may result in improved physiologic response to lung volume reduction surgery (LVRS). In this study, we compared physiologic responses of staple LVRS with combined staple/laser in a rabbit emphysema model., Methods: Ninety-three New Zealand White rabbits underwent emphysema induction with aerosolized elastase 4 weeks before surgery and were killed 1 week after surgery. Treatment groups were bilateral moderate volume staple LVRS (< or =3 g, n = 39), combined moderate volume staple (< or =3 g)/holmium laser LVRS (n = 18), large-volume staple LVRS (> or =3 g, n = 27), or sham surgery (n = 9)., Results: Decrease in postoperative static respiratory system compliance by combined moderate-volume staple/laser treatment (1.22 cc/cm H2O) was similar to large-volume staple resection (1.40 cc/cm H2O, p = 0.39), and superior to moderate staple resection (0.82 cc/cm H2O, p = 0.01) or sham surgery (0.09 cc/cm H2O, p = 0.0001). Functional residual capacity decrease was greater after combined moderate staple/laser resection (6.46 cc) than large-volume staple resection (4.52 cc, p = 0.33), moderate-volume staple resection (4.59 cc, p = 0.43), or sham surgery (4.10 cc, p = 0.29). Perioperative mortality was highest after laser/staple LVRS (22%, 4/18)., Conclusions: In this rabbit model, combined staple/ holmium laser reduction for emphysema results in significant improvement in compliance and trends toward improvement in functional residual capacity above staple reduction alone, but with higher mortality.

Although severe congenital cystic changes (CCC) of the lung may be fatal, less severe forms may regress or vanish spontaneously. With recent advances in sonography, asymptomatic CCC are increasingly found. Whether all CCC should be promptly excised, or not, is uncertain. Congenital cystic changes conceptually are bronchopulmonary foregut malformations (BPFM) with a predilection for malignant degeneration. Among all BPFM, congenital cystic adenomatoid malformation (CCAM) is most common. We therefore searched for evidence of early malignant transformation in five surgically excised and three autopsy lungs with CCAM. By light microscopy, CCAM resembled poorly formed and dilated bronchi, bronchioles and respiratory air spaces. Four lungs had multiple nodular aggregates of mucus producing cells; the glandular component (GC). By scanning electron microscopy, GC appeared as multiple micropolyps, resembling neuroepithelial bodies. By transmission electron microscopy, GC had a surface proliferation of cells with granules of the mucous type and a basal increase in cells with owl-eyed neuroendocrine granules. The glandular component in CCAM appeared similar to the mucous cells in hyperplastic polyps of the colon and a type of mucus producing bronchioloalveolar carcinoma. Our findings support the hypothesis that CCAM is caused by dysregulated paracrine growth of mature cells and extracellular matrices and that GC could have the potential for malignant transformation. Further clinical and laboratory studies of BPFM are needed for the appropriate management of congenital cystic changes.

Clinical use of staple lung volume reduction surgery (LVRS) has proliferated for treatment of emphysema despite limited data regarding efficacy or optimal techniques. Recent studies in animal models of obstructive lung disease describe the decrease in lung compliance and increase in airway support as mechanisms of an improvement in pulmonary functions analogous to human data. We describe contrasting results in an animal model of bullous lung disease with a mixed but predominantly restrictive pattern of lung disease. Mixed restrictive and bullous lung disease was induced in 17 New Zealand white rabbits with i.v. Sephadex beads and endotracheally instilled carrageenan. Unilateral stapled lung volume reduction surgery was performed at 5 weeks postinduction of emphysema on the right lower lobe by lateral thoracotomy using a pediatric stapler. Static trans-pleural pressures were measured at 60, 40, and 20 cm3 inflation at preinduction (baseline), pre- and postoperatively, and 1 week postoperatively in anesthetized animals. Lungs were then harvested en bloc and examined histopathologically. The effects of volume reduction surgery on static lung compliance, lung conductance, and forced expiratory flows (FEF) were assessed. Five weeks after induction of lung disease, the animals had no significant change in static compliance and forced expiratory volume in 0.5 s (FEV0.5) or lung conductance compared to baseline. Immediately following LVRS, the animals showed a significant decrease in static compliance, FEV0.5, and conductance. One week postoperatively, compliance increased to approximately baseline levels along with a slight increase in FEFs and conductance toward preoperative levels. Histology examination revealed restrictive and bullous lung disease. Thus, we have demonstrated the feasibility of using an animal model for evaluation of volume reduction therapy for restrictive-obstructive lung disease. Physiologically, this model showed decrease conductance and decreased forced expiratory flows following lung volume reduction despite increased recoil. This is in contrast to increased conductance and flows seen in humans with severe emphysema following surgery and suggests that current criteria excluding patients with a significant restrictive component to their lung disease from LVRS surgery may be justified.

The lung and heart, the vital organs, have to be protected and also have to move and change volume continuously to function. For the best protection and function of the lung, the thorax is shaped almost like a bellows with the diaphragm as the moving part. Furthermore, the outer surface of the lung and the inner surface of the protective thoracic cage are covered by an elastic, serous, and lubricating membrane to form the pleural cavity. This is almost like inserting a sealed-wet and stretchable-plastic bag between the lung and the thoracic wall and diaphragm to decrease friction. The lubrication is accomplished by the facing mesothelial cells that have bushy-surface microvilli enmeshing hyaluronic acid-rich glycoproteins. The amount of fluid in the pleural cavity is regulated by the hydrostatic-osmotic pressure relationship and pleuro-lymphatic drainage. Excess fluid, large particles, and cells in the pleural cavity are removed through preformed stomas assisted by respiratory movements. The stoma is found only in the anterior lower thoracic wall and diaphragm and is like the drain of a sink. Finally, clinical and subclinical injuries of the pleura appear to occur often. Reactive mesothelial cells constantly repair the damages and keep the pleural cavity open. Without mesothelial cells, the lung cannot function properly and the pleural cavity will be quickly obliterated by fibrosis.

Study Objective: At the present time, talc administered either as a slurry or an aerosol is a popular agent for producing pleurodesis. Some investigators use iodized talc while others use plain talc. The purpose of the present study was to determine if iodized talc slurry produced a better pleurodesis in animals than did plain talc., Design: New Zealand white male rabbits were randomly assigned to receive talc slurry, 200 mg/kg, with or without the addition of 50 mg iodide intrapleurally. Approximately 10 rabbits in each group were killed 1, 2, 4, 7, 14, and 28 days after the injection. The amount and character of pleural fluid, the degree of pleural adhesions, and the microscopic changes were compared in the two different groups., Results: The pleural fluid findings, the gross adhesion score for the pleura, and the microscopic changes in the visceral pleura were essentially identical for the rabbits that received iodized talc and those that received plain talc. The injection of both plain talc and iodized talc produced a normoglycemic exudative pleural effusion that had, for the most part, disappeared by the fourth day postinjection. The amount of pleural fluid at 48 h was 3.3+/-0.6 mL in the plain talc and 2.2+/-0.5 mL in the iodized talc group. At 28 days, the mean degree of gross pleurodesis in the talc group was 2.6+/-0.2 compared with 2.3+/-0.2 in the iodized group, while the mean degree of microscopic fibrosis was 1.4+/-0.3 in the plain talc group compared with 2.0+/-0.3 in the iodized talc group., Conclusion: From this study, we conclude that the addition of 50 mg of iodide does not improve the results with talc slurry pleurodesis in rabbits.

Stapled lung volume reduction surgery (LVRS) has recently been described for treatment of emphysema. Many questions arise regarding physiologic mechanisms of response from surgical treatment of emphysema. The objective of this study was to develop an animal model for the study of lung volume reduction surgery in diffuse heterogeneous emphysema. We hypothesized that elastic recoil would increase, static respiratory system compliance would decrease, and expiratory flows would increase after lung volume reduction surgery in animals with emphysema. In the study, emphysema was induced in 31 New Zealand White rabbits (3-5 kg) with endotracheally aerosalized porcine elastase (10,000-12,000 U). Lateral thoracotomies were performed 4-6 weeks postinduction under general anesthesia and mechanical ventilatory support. Stapled volume reduction was performed on the right lower lobe using a standard multirow pediatric stapler (U.S. Surgical). Pulmonary function tests were performed at baseline (preinduction), before stapling LVRS (postemphysema induction), immediately post stapling LVRS, and 1 week poststapling. Static respiratory system compliance, flow, conductance and forced expiratory flows, and peak flows at 20 and 40 cm3 of exhaled volume were analyzed. Animals were sacrificed 1 week poststapling, and bilateral lungs were harvested for histopathology. Diffuse but heterogeneous pulmonary emphysema was seen in these animals treated with high-dose aerosolized elastase. Static compliance increased, while expiratory flows and conductance decreased after induction of emphysema. Immediately post stapled volume reduction therapy, animals had decreased static compliance. By 1 week following surgery, animals showed increased forced expiratory flows and decreased expiratory resistance, although compliance was similar to preoperative levels. In conclusion, we describe initial results in an animal model of obstructive emphysema suitable for the study of lung volume reduction surgery. Changes in pulmonary function indicate that unilateral lower lobe LVRS increases airway conductance in the rabbits. Findings from LVRS studies in animal models such as this may help explain clinical improvement following LVRS in humans.

Since 1994 an endemic of chronic obstructive pulmonary disease (COPD) has developed in Taiwan after a prevalent use of a body-weight-reducing vegetable, Sauropus androgynus (SA). All conventional treatments for COPD, including steroids and bronchodilators, had been ineffective. Studies of limited lung biopsy specimens from these patients revealed bronchiolitis obliterans. A few patients died, but many developed protracted chronic respiratory failure. Because of the chronic debilitation and ineffective conventional treatments, single lung transplants were performed as the last resort in four patients. The excised lungs revealed focal fibromuscular sclerosis and obliteration of bronchial arteries in the wall of large bronchi 4 to 5 mm in diameter with segmental necrosis of bronchi 2 to 4 mm in diameter. Bronchi immediately proximal to the necrotic zone showed fibrosis and atrophy of cartilage, bronchial glands, and smooth muscle cells; bronchioles immediately distal showed obstruction or dilatation. Most bronchi larger than 5 mm, pulmonary vessels, small bronchioles, and alveoli were little altered. The pathologic changes were most consistent with segmental ischemic necrosis of bronchi at the water-shed zone of bronchial and pulmonary circulation. The specific etiologic agent and detail of pathogenesis of this SA-related COPD needs further investigation.

Study Objectives: The objective of this study was to determine the impact of the timing of chest tube insertion on outcome for the treatment of empyema, using a new animal model of empyema., Design: A prospective, controlled randomized, blinded design was used., Setting: The study was conducted in an animal research laboratory., Patients or Participants: Sixty-six 2- to 3-kg rabbits were used in this study., Interventions: After induction of empyema, the rabbits were divided into four groups. Fourteen rabbits had chest tubes placed at 24 h after empyema induction. Seventeen rabbits had chest tubes placed at 48 h and 14 rabbits had chest tubes placed at 72 h after empyema induction. Twenty-one rabbits served as control rabbits and had no chest tubes placed., Measurements and Results: Ten days after induction of empyema, the rabbits were killed. The pleural spaces of each rabbit were examined and a gross score, pleural peel score, and a microscopic score were calculated for each rabbit. The median gross score, mean pleural peel score, and median microscopic scores were significantly higher in the rabbits that underwent late chest tube placement (72 h) relative to those that underwent early chest tube placement (24 or 48 h)., Conclusions: This study supports previous expert opinion statements and conclusions from retrospective analyses that early chest tube placement (relative to delayed chest tube placement) is beneficial for the treatment of empyema.

Objective: To determine the relative efficacy and morbidity of Ho:YAG versus Nd:YAG laser treatment of bullous lung disease in an animal model., Summary Background Data: Laser coagulation procedures for treatment of emphysematous pulmonary bullae and heterogeneous emphysema continue to evolve. The role of lasers in lung volume reduction surgery remains controversial due to issues of relative efficacy and morbidity. The Nd:YAG laser is most commonly used for these procedures. We hypothesized that the shallower penetration of the Ho:YAG laser may be better suited for laser bullae coagulation and emphysema lung volume reduction with increased efficacy and reduced lung injury., Methods: Thirty New Zealand White rabbits (15 normal rabbits; 15 with bullous lung disease) were evaluated with Ho:YAG compared to Nd:YAG laser exposures. Bullae were coagulated by either Ho:YAG or Nd:YAG treatment. In all animals (bullous-induced and normals), unaffected lung tissue in the upper lobes and contralateral lungs were treated with 5 spot exposures of Nd:YAG and Ho:YAG, each to assess depth of lung injury. Animals were sacrificed at Days 0, 7, and 21 and their lungs were examined histologically., Results: Ho:YAG and Nd:YAG exposures caused equivalent lung injury to normal lung tissue. In the acute phase, parenchymal necrosis depth was similar for both Ho:YAG and Nd:YAG (850 +/- 273 microns vs. 900 +/- 270 microns respectively, p = 0.7). By Day 7, lung necrosis depth was 925 +/- 133 microns Ho:YAG vs. 1225 +/- 235 microns Nd:YAG (p = 0.33), and lung fibrosis depth was 300 +/- 134 microns Ho:YAG vs. 558 +/- 127 microns Nd:YAG (p = 0.11). By Day 21, pulmonary parenchymal necrosis was not seen. Pleural fibrosis depth was maximal at Day 21, reaching 250 +/- 102 microns for Ho:YAG vs. 300 +/- 156 microns Nd:YAG (P = 0.88). Pleural necrosis depth was 67 +/- 42 microns Ho:YAG vs 48 +/- 34 microns Nd:YAG (p = 0.42) on Day 7 and resolved by Day 21. During surgical coagulation procedures, the Ho:YAG laser was dramatically more efficient in coagulating bullae. The Ho:YAG laser required less exposure at equivalent power and resulted in immediate desiccation of bullae, in sharp contrast to the Nd:YAG laser., Conclusions: Because the Ho:YAG was more effective and did not result in more acute lung injury than the standard Nd:YAG laser in this study, Ho:YAG lasers may have improved potential for laser treatment of bullae or lung volume reduction surgery (LVRS) compared to Nd:YAG lasers.

Subsurface perfusion to lung parenchyma underlying the pleura is difficult to assess in live ventilated animals. The purpose of this study was to assess applicability of a newly developed laser Doppler grid scanning imaging technology that measures perfusion of pleural subsurface lung regions in intact normal and abnormal animal lungs. Eighty-six Doppler grid perfusion measurements were performed in five New Zealand White Rabbits (3-5 kg); four with unilateral bullous lung disease, one normal control. Left upper lobe lung surface was exposed to 10 1-sec spot Nd:YAG exposures (70 W/cm2). One week following laser exposure, all rabbits underwent sequential bilateral open thoracotomy. Unaffected left lower lobes in these animals and all four lobes of a previously untreated rabbit were used as controls. Pleural subsurface perfusion measurements were recorded over a contiguous 900-pixel square surface grid using quantitative noncontact laser Doppler imaging during open thoracotomy procedures. Scans were obtained in a normal volume ventilation mode, at 30 cm of inspiratory hold airway pressure, and postinflation. A perfusion-pressure response curve was obtained in normal lung at 10-, 20-, and 30-cm static airway pressure. Post mortem measurements were used as 0 flow controls. Normal lung tissue was found to have relatively high pleural subsurface perfusion (1362 +/- 328 corrected units on a scale of 0-4095). Areas of atelectasis had decreased perfusion (659 +/- 512 U., 48.4 +/- 12.5% compared to normal lung, p < 0.02), but returned to normal levels after inflation of the lung (1253 +/- 363 U., p = 0.21 compared to normal). Pleural subsurface perfusion decreased uniformly and progressively as lung inflation pressure increased (p < 0.0001). Perfusion increased immediately to supranormal values following release of high inspiratory inflation pressure holds (1603 +/- 626 U., 117 +/- 18% compared to normal lung, p = 0.03). Bullae had markedly decreased perfusion (541 +/- 68 U.) that was not further reduced by increased inflation pressures. Noncontact laser Doppler grid perfusion imaging appears to provide a new tool for measuring pleural subsurface perfusion over a large area of lung surface in clinical experimental settings. Results are rapid, reproducible, and consistent. Sampling errors inherent in current point sampling Doppler flow techniques are reduced by the multiple contiguous measurements. We have used this technique to demonstrate inspiratory pressure-related reduction in pleural subsurface perfusion in normal lung, reversible decreased perfusion in atelectatic regions, and reduced perfusion in bullous and laser-treated lung regions.

In the 1960s, a close relationship between heavy exposures to crocidolite asbestos and mesothelioma was established. The debate on the diagnosis of mesothelioma became complicated because of the possibility of litigation. Well differentiated mesothelioma cells are mucicarmine negative but alcian blue and periodic acid-Schiff (PAS) positive, which are removed by hyaluronidase and diastase digestion. By electron microscopy (EM), they show bush-like elongated, slender, and branching microvilli. By immunohistochemistry they express both keratin and vimentin but not carcinoembryonic antigenicity (CEA), B72.3, Ber-EP4, and Leu-M1. In poorly differentiated mesotheliomas, chromosomal and molecular biological alterations are common and complex but these alterations also overlap with that of poorly differentiated tumours of the lung and other organs. A poorly differentiated pleural tumour is most likely metastatic and needs good team work to locate the primary site. The diagnosis of a mesothelioma and asbestosis should be established separately. Future studies will be focused less on the phenotypic differences but more on the broad molecular and multi-phasic mechanisms of carcinogenesis, irrespective of the aetiological agents, in poorly differentiated tumours.

Platelet-derived growth factor (PDGF) is postulated to play a role in the pathophysiology of pulmonary fibrosis. Recombinant human PDGF-BB administered as a single intratracheal injection in rats causes an increase in peribronchial and perivascular stromal cells on days 2 and 3 after injection as evaluated by hematoxylin and eosin histology and 5-bromodeoxyuridine incorporation. Proliferation of bronchial epithelial cells and arterial smooth muscle cells, although not evident by routine histological examination alone, is detected on days 2 and 3 by increased 5-bromodeoxyuridine incorporation. A mild increase in 5-bromodeoxyuridine labeling is observed in peripheral alveolar parenchyma after injection of PDGF. The proliferative peribronchial and perivascular mesenchymal cells appear by light microscopic and ultrastructural criteria to be fibroblasts that are immunoreactive for vimentin but negative for alpha-smooth muscle actin and desmin. Daily intratracheal injection of PDGF-BB for 3 days causes a slightly more pronounced peribronchial and perivascular spindle cell proliferation accompanied by collagen deposition as evaluated by Masson's trichrome stain. PDGF-induced increases in cellularity and collagen resolve within 5 days after the last PDGF injection. In conclusion, intratracheal injection of PDGF-BB causes transient proliferation of pulmonary mesenchymal and epithelial cells accompanied by collagen deposition.

Epithelioid angiosarcoma of the bone represents a challenging diagnosis by bone marrow biopsy. We present a case of a multicentric high grade angiosarcoma of the bone with epithelioid features. On the basis of the clinical presentation, the radiological findings, and the appearance of loosely clustered tumor cells detected in the initial bone marrow biopsy, the main differential diagnoses considered were a poorly differentiated non-secretory multiple myeloma and metastatic carcinoma. Subsequent morphologic, immunohistochemical and electron microscopic examination of tissue samples clarified the nature of the tumor as epithelioid angiosarcoma. We discuss potential pitfalls in clinical and morphological diagnosis. The strong reactivity of the tumor cells with the nonspecific but ubiquitous mesenchymal marker vimentin in similar cases should direct early attention to the rare malignant bone tumor, epithelioid angiosarcoma, with subsequent confirmation of this diagnosis with specific immunohistochemical endothelial cell markers and/or electron microscopy.

Background and Objective: Thoracoscopic laser techniques have been described for treatment of pulmonary bullae. Clinical application of this procedure has proliferated despite limited data regarding efficacy or optimal techniques. The objective of this study was to develop an animal model for investigating laser treatment of bullous lung disease., Study Design/materials and Methods: Sixty-two New Zealand White rabbits (3-5 kg) were injected intravenously with 0.35 cc sterile-filtered Sephadex G-100 beads (1 g/100 cc suspension). Three hours later, rabbits were anesthetized, intubated, and 10 cc 0.7% heat-treated or 1% untreated carrageenan solution was instilled endotracheally into a catheter wedged in a mainstem bronchus., Results: Bullae formed over 4-6 weeks in 33% of the animals treated with 0.7% heat-treated carrageenan, and 90% of animals receiving 1% untreated carrageenan (P < 0.005) as demonstrated by serial thoracoscopy. Thoracoscopy was performed at 6-8 weeks using 5 mm trocars under general anesthesia and mechanical ventilatory support. Animals developed pulmonary bullae ranging in size from 0.5 to 2 cm. Bullae were ablated under thoracoscopic visualization using a CO2 laser with a 4 mm OD rigid probe and short focal length in a defocused mode, or an Nd:YAG laser with a 0.4 mm diameter flexible fiberoptic probe. Animals recovered quickly following thoracoscopy., Conclusion: We have successfully developed an animal model for thoracoscopic laser ablation of emphysematous pulmonary bullae. This animal model should be useful in investigating treatment of bullous lung disease in humans.

Background and Objective: Laser techniques have recently been described for treatment of patients with emphysema and bullous lung disease. Laser exposure of the pulmonary parenchyma during these procedures is complicated by laser-induced lung injury with substantial associated morbidity. Animal investigations are needed to develop methods that reduce lung injury. We hypothesized that the depth of injury could be reduced by pulsing laser exposures, with the goal of limiting thermal effects to more superficial tissue levels. In this study, we compared acute and chronic histologic injury resulting from pulsed- versus continuous-mode CO2 and Nd:YAG laser pulmonary parenchymal exposures in rabbits., Study Design/materials and Methods: A total of 40 New Zealand White (NZW) rabbits underwent thoracotomy followed by exposure with CO2 laser (n = 10 continuous vs. n = 10 pulsed at 250 Hz with duty cycle 0.15 ms) or ND:YAG laser (n = 10 continuous vs. n = 10 pulsed at 10 Hz with duty cycle 0.10 sec) to the visceral pleural surface using 1 minute of laser exposure (5 watts, defocused to 70 W/cm2 power density) to the exposed lung surface. Rabbits were sacrificed at 4 and 21 days post-injury, and lungs were examined histologically., Results: CO2 and Nd:YAG laser treatment resulted in substantial pulmonary parenchymal injury. While CO2 laser-induced damage was distinct from Nd:YAG histologically, pulsed-mode laser exposures did not reduce lung injury for either laser. Acute edema occurred to depths of 1180 +/- 338 microns for continuous-mode CO2 laser exposures compared to 1,340 +/- 430 microns in pulsed mode (p = .77). For Nd:YAG laser exposure, acute edema depth was 750 +/- 748 microns continuous versus 1120 +/- 367 microns pulsed mode (p = .65). Chronic lung fibrosis depth was 450 +/- 164 microns for CO2 continuous mode compared to 575 +/- 170 microns in pulsed mode (p = .61). Lung fibrosis depth for Nd:YAG was 550 +/- 96 microns, continuous versus 484 +/- 180 microns pulsed mode (p = .76)., Conclusion: The similarity in injury between pulsed- and continuous-mode exposures suggests that thermal relaxation times are long relative to the selected pulse frequencies in intact living rabbit lungs. Alternatively, brief high-energy pulsations may increase focal temperatures with a tendency to increase injury depth relative to the penetration of the laser light. Thus, pulsed laser modes in these settings appear to be ineffective in reducing laser-induced lung injury in clinical settings.

Tetracycline has been one of the most commonly used agents for producing a pleurodesis. However, it is no longer available due to more stringent requirements on the manufacturing process. The objective of this project was to determine whether Corynebacterium parvum is an effective sclerosant in an experimental model in rabbits. The following medications were instilled intrapleurally in anaesthetized male rabbits: tetracycline 35 mg.kg-1 or C. parvum 4 or 8 mg, all diluted with bacteriostatic saline solution. Twenty eight days after the instillation, the animals were sacrificed and the pleural spaces assessed macroscopically for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The intrapleural injection of C. parvum was ineffective in creating pleural fibrosis. The mean degree of pleurodesis in the 10 rabbits who received tetracycline was 3.5 +/- 0.7 (scale 0-4) whilst in the 10 rabbits that received 4 mg C. parvum it was 0.0 +/- 0.0, and in the 10 rabbits that received 8 mg C. parvum it was 0.5 +/- 0.8. Based on this study, we recommend that C. parvum should not be used as a pleural sclerosant in patients with normal pleura.

Insufflated talc is probably the most effective agent for creating a pleurodesis both in the clinical situation and in animals. However, the insufflation of talc requires an invasive procedure such as thoracoscopy or thoracotomy. Recently, there have been reports that talc in a slurry was effective in the clinical situation. The objective of this project was to determine whether talc in a slurry at varying doses is an effective sclerosant in an experimental model in rabbits. Talc, 50, 100, 200, and 400 mg/kg, in a 2-mL slurry was injected intrapleurally through a small catheter in male rabbits. Eleven rabbits received each dose. Twenty-eight days after the instillation, the animals were killed. The pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The degree of pleurodesis (on a scale of 0 to 4) after the injection of 50, 100, 200, and 400 mg/kg of talc was 1.1 +/- 0.9, 1.5 +/- 1.1, 2.7 +/- 0.6, and 3.4 +/- 0.5, respectively. The degree of microscopic fibrosis similarly increased with increasing doses of talc. These scores were similar to those we have reported with the tetracycline derivatives. In contrast to the results with tetracycline derivatives, none of the rabbits developed fibrothorax or hemothorax. From this study, we conclude that talc in a slurry is a very effective pleural sclerosant in rabbits and does not produce hemothoraces as do the tetracycline derivatives.

The gene frequencies of ADH2(2) and ALDH2(2) were lower in Tibetan and Mongolian populations than in Vietnamese, Han Chinese, and three Chinese minority populations.

Parenteral tetracycline, one of the most commonly used agents for producing pleurodesis, is no longer available because of stricter regulations governing the manufacturing process. The objective of this project was to determine whether minocycline, a tetracycline derivative, is an effective sclerosant in an experimental model in rabbits. We also studied the relationship of the dose and the volume injected to the degree of pleurodesis. The following medications were instilled intrapleurally in anesthetized male rabbits: tetracycline, 35 mg/kg; or minocycline, 4, 7, 10, or 20 mg/kg, diluted to a total volume of 1 or 2 ml of bacteriostatic saline solution; or minocycline, 40 mg/kg, diluted to a total volume of 2 ml of the solution. Twenty-eight days after the instillation, the animals were killed. The pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The degree of pleurodesis grossly and microscopically after the injection of 7, 10, 20, or 40 mg/kg of minocycline was comparable to that after the injection of 35 mg/kg of tetracycline, while the dose of 4 mg/kg was less effective. In the animals who received the higher doses of minocycline intrapleurally (ie > or = 20 mg/kg), there was an excess mortality both early (chi 2 = 3.61, 0.05 < p < 0.10) and late (chi 2 = 11.0, p < 0.005) which appeared to be related to the development of hemothorax. The intrapleural injection of the tetracycline derivatives was significantly (p < 0.05) more effective when the total volume of the solution was 2 ml rather than 1 ml. The present study demonstrates that minocycline is an effective agent for producing pleurodesis in the rabbit. Minocycline given intrapleurally at doses of 7 mg/kg or above is comparable to tetracycline, 35 mg/kg. Higher doses of minocycline (> or = 20 mg/kg) produce a high mortality that seems to be related to hemothorax. Since, in humans, a large experience confirms only 20 mg/kg of tetracycline is needed to produce adequate pleurodesis safely, we recommend a dose of 4 mg/kg of minocycline for the production of pleurodesis.

Pleuritis or pleural effusion frequently develops in patients with pneumonia or heart failure. Most of these pleural changes regress without intrapleural intervention. The detailed mechanisms of the regression of the pleural changes in humans are not well documented. We studied the parietal pleura of nine patients with lung cancer and two patients with coronary artery disease by scanning electron microscopy (SEM). All patients had neither radiographic nor gross evidence of pleural disease but all had mixed surface alterations by SEM. Focal denudation of mesothelial cells was common. Deeper injuries exposed thick and thin interweaving collagen bundles. Patchy depositions of amorphous or crystallized fibrin covered normal and damaged pleural surfaces, frequently admixed with macrophages, red blood cells, and tissue debris. Reactive mesothelial cells appeared to proliferate over the fibrin. Our findings suggest that subclinical pleural alterations occur often in patients with pulmonary or cardiac diseases and that an intact pleural surface in those patients is restored mainly by the proliferation of reactive mesothelial cells.

The two agents most commonly used for producing a pleurodesis are tetracycline and bleomycin. Tetracycline is no longer available due to more stringent requirements on the manufacturing process. The objective of this project was to determine whether bleomycin is an effective sclerosant in an experimental model in rabbits. The following medications were instilled intrapleurally in anesthetized male rabbits: tetracycline, 35 mg/kg, or bleomycin, 1.5 or 3.0 IU/kg diluted to a total volume of 1 ml with bacteriostatic saline solution. Twenty-eight days after the instillation, the animals were killed, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The intrapleural injection of bleomycin was ineffective in creating pleural fibrosis, either grossly or microscopically. The mean degree of gross pleurodesis in the six rabbits who received tetracycline was 2.7 +/- 1.5 (scale 0 to 4), while that in the rabbits who received the highest dose of bleomycin was 0.0 +/- 0.0. Based on this study, we recommend that bleomycin not be used as a pleural sclerosant in patients with nonneoplastic pleural disease, eg, those with pneumothorax, congestive heart failure or cirrhosis, and pleural effusion.

Even though the eosinophil is potentially an important contributor to airway narrowing during the late allergic airway response, direct evidence of its participation is lacking. Therefore, we examined the effects of eosinophilia induced by Sephadex on the magnitude of the late airway response of sensitized rats following allergen challenge. Brown Norway rats were actively sensitized to ovalbumin (OA). At the same time and 14 days later, a test group was administered Sephadex G200 (0.5 mg intravenously). The animals were challenged with an aerosol of OA and pulmonary resistance (RL) was measured over 6 h. The early response to OA reached a peak more rapidly and the magnitude of the late response, measured as the area under the curve of RL against time, was significantly greater in the Sephadex-treated group (48.3; geometric mean) compared to the control animals (18.9; p < 0.02). The percentage of eosinophils was increased in the bronchoalveolar lavage of Sephadex-treated animals (4%) compared to the controls (0.9%; p < 0.02) following OA challenge. These results demonstrate that Sephadex induces eosinophilia in Brown Norway rats and is associated with an increase in the late allergic airway response. This is consistent with the hypothesis that the eosinophil is an important determinant of the late response.

An in situ optical probe was developed to measure reliably the local specific interfacial area of the suspended phase (specifically air bubbles) in a bioreactor. The light transmission-based probe can be simply and inexpensively constructed from readily available components. The probe's performance was tested in a suspension of opaque monodisperse polystyrene spheres as well as in the presence of nonspherical, nonuniformly distributed bubbles. The probe signal is directly related to the local specific interfacial area by a calibration equation obtained with polystyrene beads, as opposed to the cumbersome direct photographic bubble measurements that the probe attempts to replace. Its utility was demonstrated by measuring the specific bubble interfacial area at two locations in a bioreactor at various agitation intensities.