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Transcatheter arterial chemoembolization therapy with epirubicin hydrochloride, mitomycin C-iohexol-Lipiodol emulsion (EMILE) for hepatocellular carcinoma.

The efficacy of transcatheter arterial Lipiodol chemoembolization (TALCE) using epirubicin hydrochloride, mitomycin C-iohexol-Lipiodol emulsion (EMILE) for hepatocellular carcinoma (HCC) was assessed retrospectively. EMILE was confirmed to have characteristics of fair dispersibility, stability, and slow drug release in vitro prior to clinical administration. TALCE without EMILE (simple infusion of anticancer drugs and Lipiodol) and with EMILE were preoperatively performed in two groups of candidates for hepatectomy, consisting of 17 patients each (non-EMILE and EMILE groups). Mean percentages of Lipiodol retention area to tumor area on computed tomographic (CT) scan following TALCE were 46.8 +/- 38.4% and 91.5 +/- 13.2% (mean +/- SD), respectively (P = 0.0005). Mean percentages of necrotic area to tumor area determined on histologic study of specimens were 42.9 +/- 43.8% and 63.2 +/- 44.0%, respectively (NS). In conclusion, TALCE with EMILE brought about longer retention of Lipiodol in HCC; however, gelatin sponge cubes and a higher dose of epirubicin hydrochloride were more significantly related to tumor necrosis than treatment with EMILE.

Adult↗

Inflammation effects on the electrical properties of atrial tissue and inducibility of postoperative atrial fibrillation.

BACKGROUND: Atrial fibrillation is the most common complication after cardiac surgery. Postoperative atrial fibrillation (PAF) has been shown to increase length of stay, morbidity, and mortality. Because the clinical behavior of PAF parallels that of inflammation following surgery, we investigated the effect of the inflammatory mediator arachidonic acid on the electrical behavior of normal atrial tissue in vitro and assessed the efficacy of the topical application of anti-inflammatory drugs at suppressing PAF in an animal model. METHODS: To study changes in electrical behavior from inflammation, the conduction properties of six normal canine right atrial appendages were quantified as a function of the direction of impulse propagation with and without 80 mum arachidonic acid. To study the effect of topical anti-inflammatory drugs, 24 adult mongrel dogs were prepared according to the model of sterile talc pericarditis. Nine dogs received talc alone (T), seven received talc combined with 600 mg ibuprofen (T + I), and eight received talc combined with 10 mg methylprednisolone (T + M). Three days following preparation, programmed electrical stimulation was performed to quantify conduction characteristics and to attempt the induction of atrial fibrillation (AF). RESULTS: In vitro, arachidonic acid produced an anisotropic and rapidly reversible 36.1 +/- 3.4% (P = 0.01) decrease in conduction velocity transverse to the long axis only. In vivo, both ibuprofen and methylprednisolone significantly reduced the incidence of sustained AF (from 56 to 0% T + I and 12% T + M, respectively, P = 0.02). No differences in conduction velocities or refractory periods were seen during sinus rhythm among the groups. CONCLUSIONS: Acute inflammation as mimicked by arachidonic acid slows conduction anisotropically, mainly transverse to the long axis of the atrial myocardial fibers. This may set the stage for reentry. Preventing inflammation in vivo by the topical application of anti-inflammatory drugs supports this hypothesis, suggesting a possible role for inflammation in the genesis of postoperative atrial fibrillation and shedding light on the mechanism underlying PAF.

Animals↗

Malignant pleural effusions.

The estimated annual incidence of malignant pleural effusions in the United States is 150,000 cases. Patients most commonly present with dyspnea, initially on exertion and later at rest. Chemical pleurodesis is the most common modality of therapy for patients with recurrent, symptomatic, malignant pleural effusion. Talc is the most successful pleurodesis agent, and talc poudrage and slurry have equal efficacy. Although a number of cases of acute respiratory failure have been associated with talc pleurodesis, the incidence is < 1% and many of these episodes cannot be clearly attributed to talc alone. Although a low pleural fluid pH is associated with a decreased survival and less successful pleurodesis, pH should not be the sole criterion for recommending or withholding pleurodesis. Other factors that need to be considered before recommending pleurodesis include relief of dyspnea after therapeutic thoracentesis, general health of the patient, performance status, presence of trapped lung, and the primary malignancy. Pleuroperitoneal shunt or chronic indwelling catheter should be considered for patients who fail pleurodesis or who have a trapped lung.

Journal Article↗

Hepatic hydrothorax.

Hepatic hydrothorax (HH) is an uncommon manifestation of cirrhosis with ascites. Pleural effusions form when ascitic fluid moves through diaphragmatic defects that have been opened by increased peritoneal pressure. The diagnosis is established clinically by finding a serous transudate and is confirmed by radionuclide imaging demonstrating communication between the peritoneal and pleural spaces. In end-stage liver disease, the management of hepatic hydrothorax is problematic and often does not respond to medical therapy. Therapeutic options for a refractory hepatic hydrothorax include therapeutic thoracentesis, talc slurry through a chest tube, peritoneovenous and pleurovenous shunting, thoracoscopic talc poudrage, transjugular intrahepatic portosystemic shunt (TIPS), thoracosopic diaphragmatic defect repair followed by talc poudrage, and lastly, liver transplant. TIPS can be used as a bridge for transplantation but is often complicated by encephalopathy. Video assisted thoracic surgery (VATS) with patching the defect and talc poudrage may provide symptomatic relief; however, the morbidity and mortality in these extremely ill patients is high. The only definitive treatment for refractory hepatic hydrothorax associated with end-stage cirrhosis is liver transplantation.

Journal Article↗

Effect of conditioning, betaine, and sucrose on survival of rhizobacteria in powder formulations.

To assess the feasibility of simplified dry formulations of beneficial rhizobacteria with improved shelf life, strains of Pseudomonas and members of the family Enterobacteriaceae were conditioned by either aging, exposure to osmotica, or growth on media amended with sucrose or betaine. Strains thus treated were formulated in 1% methylcellulose and talc, and survival was assessed over 10 to 12 months. Survival of 24-h-old cultures of the same strains suspended in 20% xanthan gum and talc over the same interval was used as the standard of comparison. The survival of strains treated with sucrose, with or without betaine, and formulated in methylcellulose and talc was equal to or greater than that of 24-h-old cultures suspended in 20% xanthan gum and talc. Aging of strains on unamended King's medium B, growth of strains on KCl-amended media, and addition of betaine to KCl-amended King's medium B, whether or not strains were suspended in buffer or a diluent isosmotic to culture conditions, failed to improve survival of the strains tested. The practicality of specific amendments, such as sucrose or other disaccharides, for promoting survival of beneficial bacteria in simplified dry formulations was thus demonstrated.

Journal Article↗

Medial medullary syndrome in a drug abuser.

A 28-year-old woman with a long history of drug abuse experienced flaccid quadriplegia and bilateral loss of posterior column sensation a few minutes after an intravenous (IV) injection of methylphenidate hydrochloride. Subsequently, spasticity developed and she showed minimal functional improvement during a period of several months. Necropsy performed 8 1/2 months later showed systemic granulomatosis due to talc and two ischemic infarctions, one involving both medial medullary areas and the other involving the left frontal lobe. Deposits of talc, presumably from a medication prepared for oral use, were demonstrated in the small vessels in the area of the medullary infarction. This case is unique in that the medial medullary syndrome was apparently caused by an embolus of talc following its IV administration.

Adult↗

Suture contamination by surface powders on surgical gloves.

Recent studies have shown that many glove manufacturers still are using talc as a glove-mold release agent. The removal of talc particles from the patient-contact side of the gloves is difficult and incomplete with the use of recommended washing and wiping procedures. As a result, a shedding hazard exists that may ultimately be related to granulomatous reactions. In our study, shedding was demonstrated to be hazardous because of suture contamination with talc particles.

Gloves, Surgical↗

Control of pleural effusions in patients with breast cancer. A randomized trial.

In a controlled randomized trial, 46 patients with pleural effusions secondary to breast cancer were treated at first diagnosis with either intracavitary mustine or talc, to determine which agent produced the more effective pleurodesis. Of the 37 evaluable patients, control of the effusion was achieved in 9/17 (56%) of those treated with mustine and 18/20 (90%) of the talc group (P less than 0.025). This suggests that early treatment with intracavitary talc can effectively palliate this complication of breast cancer.

Breast Neoplasms↗

Structural changes of cytochrome c(552) from Thermus thermophilus adsorbed on anionic and hydrophobic surfaces probed by FTIR and 2D-FTIR spectroscopy.

The structural changes of cytochrome c(552) bound to anionic and hydrophobic clay surfaces have been investigated by Fourier transform infrared spectroscopy. Binding to the anionic surface of montmorillonite is controlled by electrostatic interactions since addition of electrolyte (0.5 mol L(-1) KCl) causes desorption of more than 2/3 of the protein molecules. Electrostatic binding occurs through the back side of the protein (i.e., remote from the heme site) and is associated only with subtle changes of the secondary structure. In contrast, adsorption to the hydrophobic surface of talc leads to a decrease in alpha-helical structure by ca. 5% and an increase in beta-sheet structure by ca. 6%. These structural changes are attributed to a hydrophobic region on the front surface of cytochrome c(552) close to the partially exposed heme edge. This part on the protein surface is identified as the interaction domain for talc and most likely also serves for binding to the natural reaction partner, a ba(3)-oxidase. Fourier transform infrared spectra of cytochrome c(552) and the clay-cytochrome c(552) complexes have been measured as a function of time following dissolution and suspension in deuterated buffer, respectively. A two-dimensional correlation analysis was applied to these spectra to investigate the dynamics of the structural changes in the protein. For both complexes, adsorption and subsequent unfolding processes in the binding domains are faster than the time resolution of the spectroscopic experiments. Thus, the processes that could be monitored are refolding of peptide segments and side chain rearrangements following the adsorption-induced perturbation of the protein structure and the solvation of the adsorbed protein. In each case, side chain alterations of solvent-exposed tyrosine, aspartate, and glutamate residues were observed. For the cytochrome c(552)-talc complex, these changes are followed by a slow refolding of the peptide chain in the binding domain and, subsequently, a further H/D exchange of amide group protons.

Adsorption↗

Video-assisted management of malignant pleural effusion in breast carcinoma.

BACKGROUND: Advanced breast carcinoma almost always leads to a malignant pleural effusion, conditioning the performance status of patients and consequently quality of life. The treatment of malignant pleural effusion should be a priority in the management of such patients. The results of video-thoracoscopic approach (VATS) chemical pleurodesis was analyzed in patients with recurrent pleural effusion from breast carcinoma. METHODS: From October 1998 to June 2004, 71 consecutive patients with breast carcinoma-related pleural effusion were treated by the same thoracic-surgeon team with intracavitary nebulization of 8 g of asbestos-free sterilized talc via VATS. Multiple pleural biopsies were performed to determine biologic characteristics of recurrent disease. RESULTS: Talc pleurodesis was performed in all cases, with no intraoperative or postoperative complications. Median length of hospital stay was 5 days (range, 5-8). The overall success rate of the surgical procedure was 89% (confidence interval [CI], 79-95%) with a mean follow-up of 22 months (range, 2-81 mos). The overall survival time was 17 months (range, 2-80). Biopsies showed a switch on receptor status and c-erB-2 status from negative (primary tumor) to positive (pleural metastasis) in 11 (15%) patients. In another 7 (9.8%) patients, we obtained completely new information that was hitherto unknown. CONCLUSION: Talc pleurodesis via VATS is an effective and safe procedure that yields a high rate of success at the first attempt and achieves long-term control of malignant pleural effusion due to breast carcinoma. Concomitant biopsies performed during the VATS procedure were a determining factor in the subsequent decision-making process.

Adult↗

Management of malignancy-associated pleural effusion: current and future treatment strategies.

Management of recurrent malignant pleural effusion, a common complication of malignancy, poses a challenge to clinicians. Although almost one century has elapsed since the introduction of the pleurodesis procedure, the ideal approach and best agent are still to be defined. Optimally, pleurodesis should be done at the bedside with a minimally invasive procedure, and suitable agents to achieve pleural symphysis should be inexpensive, available worldwide and free of adverse effects. To date, no substance completely fulfills these requirements. Silver nitrate should be considered for pleurodesis because of its low cost and ease of handling. Although talc has been used most frequently to induce pleurodesis, reports of death due to acute respiratory failure have raised concerns about the safety of this agent. Tetracycline, an effective alternative used in the past, is no longer commercially available. This agent has been substituted with derivatives of tetracycline, such as minocycline and doxycycline with success rates similar to those with tetracycline. Several antineoplastic agents have been injected into the pleural space with the aim of producing pleural symphysis, the most representative of this group being bleomycin. Recent knowledge of the molecular mechanisms involved in pleural inflammation has brought into focus new substances, such as transforming growth factor beta and vascular endothelial growth factor, which may be used as pleurodesis agents in the future. Nevertheless, more studies are necessary to better define the potential of these substances in the induction of pleural symphysis.Ideally, a sclerosing agent should be cost-effective, available worldwide and easily administered. Talc will probably stand as the preferred agent to be used for pleurodesis in malignant pleural effusion because of its efficacy, easy manipulation and handling. However, further investigation is necessary to minimize adverse effects related to talc.

Anti-Bacterial Agents↗

Pleural sclerosis for the treatment of pneumothorax and pleural effusion.

Pleural sclerosis is indicated to obliterate the pleural space when one wants to prevent the recurrence of a spontaneous pneumothorax or the reaccumulation of a pleural effusion. Although many different agents ranging from antibiotics to antiseptics to antineoplastics to talc have been advocated, none is ideal. It is interesting that in the era when we are mapping the human genome, the agent most commonly used for pleurodesis is talc. Talc is very inhomogeneous, and the mechanisms by which it produces pleurodesis are unknown. In this review we will discuss the theory and mechanism of pleurodesis, the indications and contraindications for it, the advantages and disadvantages of the agents presently used for it, and our recommendations for the procedure.

Adjuvants, Immunologic↗

MRI evaluation of infectious and non-infectious synovitis: preliminary studies in a rabbit model.

BACKGROUND: Literature on magnetic resonance imaging (MR) evaluation of inflammatory joint effusions is sparse. OBJECTIVE: To describe an animal model for studying infectious and non-infectious joint effusions with magnetic resonance imaging. MATERIALS AND METHODS: Ten rabbit knees with septic arthritis and four with talc synovitis were imaged with MR. Contralateral knees injected with saline served as controls. Fat saturation T2-weighted and gadolinium-enhanced T1-weighted images were assessed for joint effusion, and periarticular and adjacent intraosseous increased signal or enhancement. Each knee was cultured and underwent pathologic examination. RESULTS: Both Staphylococcus aureus and talc produced effusions in all knees. The degree of periarticular signal and enhancement was greater in infected knees than talc-injected knees. No abnormal enhancement was seen within bone. Pathologic examination showed a greater degree of inflammation and joint destruction in the infected knees, but no evidence of osteomyelitis. CONCLUSION: A greater degree of abnormal signal and enhancement seen on MR suggests a more vigorous inflammatory process, as seen with septic arthritis. In spite of advanced septic arthritis, no enhancement was evident within bone, suggesting that enhancement within bone is not an expected finding in isolated septic arthritis and should raise concern for osteomyelitis.

Animals↗

Thoracoscopic palliative treatment of malignant pleural effusions: results in 273 patients.

BACKGROUND: The aim of this study was to analyze the results of pleurodesis for malignant pleural effusion performed by surgeons. PATIENTS AND METHODS: A series of 273 patients with malignant pleural effusion underwent thoracoscopy with the aim of performing a palliative pleurodesis. There were 94 males (34.4%) and 175 females (64.1%), ranging in age from 15 to 94 years (mean age: 60.6 years). The effusion was on the right side in 136 patients (49.8%), on the left side in 110 (40.3%), and bilateral in 27 (9.9%). Thoracoscopy was performed under general anaesthesia in all patients. Pleural biopsy was performed in two thirds of the patients (70.7%). Pleurodesis was produced by instillation of 5g of sterile asbestos-free talc; the chest tube was left in place a minimum of 3 days. It was removed when fluid drainage was less than 200 ml/24 h. Patients were usually discharged the day after chest tube removal. RESULTS: There was no intraoperative mortality. Two patients (0.7%) had intraoperative complications; 17 (6.2%) underwent a bilateral pleurodesis, and 10 (3.7%) had a pericardiopleural window. In 32 patients (11.7%) no pleurodesis was done, either because the lung did not properly re-expand (5.2%), or because of suspected infection, e.g., false membranes (1.9%), or because of multiple adhesions (4.6%). Finally, only 241 patients (88.3%) had a talc poudrage at the time of thoracoscopy. Duration of postoperative pleural drainage ranged between 1 and 11 days (mean: 3.64 days). The postoperative hospital stay ranged from 2 to 21 days (mean: 7.1 days). Pleural empyema occurred in 4 patients (1.5%) and was lethal in one patient. The mean follow-up period was 8.39 (7.2 months, and 172 patients had regular follow up. In this group, there were 24 recurrences (14%), 12 of which were treated by repeat pleurodesis. The results were very good in 133 patients (77.3%), acceptable in 35 patients (20.3%), and there was a failure in 4 patients (2.4%). CONCLUSIONS: Results of surgical thoracoscopy for malignant pleural effusion are good, with low morbidity. However, in debilitated patients, bedside talc slurry may be preferable.

Adolescent↗

Pneumothorax in cystic fibrosis: a 26-year experience.

We reviewed the records of all patients with cystic fibrosis and radiologically demonstrated pneumothorax at Rainbow Babies and Childrens Hospital between 1959 and 1987. There occurred 144 pneumothoraces, 71 right and 73 left, in 99 patients, 48 female and 51 male. The median survival from the date of the first pneumothorax was 29.9 months. Primary therapy included the following: observation; tube thoracostomy; tube thoracostomy with instillation of quinacrine hydrochloride, tetracycline, silver nitrate, or talc; or partial pleurectomy. Complications were minimal in each group. The surgical group did significantly better than all other groups except the group given talc. We conclude that pneumothorax is a late and ominous complication of cystic fibrosis. The primary treatment of pneumothorax should be partial pleurectomy. Talc instillation should be reserved for patients in respiratory failure who are too ill to undergo operation and for the occasional patient in whom surgical intervention fails.

Adolescent↗

Abdominal wall thickness as a means of assessing peritoneal fibrosis in mice.

Herein we describe a method for the quantitative assessment of connective tissue deposition within the peritoneal cavity. Female C57BL/6 mice (8-10 weeks) were given a single intraperitoneal injection of varying concentrations of talc (100 mg, 50 mg, 30 mg, 20 mg) in 1 ml of PBS or PBS alone. After 14 days, animals were killed. Adhesion formation was measured by the standard method of Myllârniemi et al. (1966), namely a gross visual inspection of the peritoneal cavity. This analysis gave a crude assessment of connective tissue deposition in the abdominal cavity but did not allow one to distinguish more subtle differences between intermediate dosage groups. In addition, a histological evaluation was performed. For the latter method, portions of the abdominal wall of mice were fixed and processed for histological analysis using Masson's Trichrome stain which allows for differentiation of connective tissue components. The thickness of connective tissue between the parietal peritoneum and the underlying abdominal wall muscle was measured. A dose-dependent increase in connective tissue deposition was observed in talc-treated animals compared to saline control animals. A differential cell count of the peritoneal exudate cells (PEC) showed that there was no change in cell populations in talc treated animals (compared to control animals). Given the above results, the measurement of connective tissue thickness was found to give the most accurate assessment of peritoneal fibrosis than other previously used methods.

Abdominal Muscles↗

Long-term peritoneal tissue response in rats to mould-release agents and lubricant powder used on surgeons' gloves.

Following implantation of 50-mg samples of a starch powder used for glove lubrication, or of talc or calcium carbonate mould-release agents for gloves, in the peritoneal cavity of rats, the treated animals were killed in groups of ten after 2, 4, 8, 13, 26 and 52 wk and were examined. Groups of sham-operated animals were used as controls. Within each treatment group the frequency of peritoneal adhesions remained constant throughout the study. Talc produced significantly more adhesions than the other treatments and caused a more severe granulomatous reaction, which persisted. Calcium carbonate and starch powder produced similar numbers of adhesions and in both cases the residues became invested by a thin fibrous capsule. Calcium carbonate appeared a safer material than talc.

Animals↗

Small size new silastic drains: life-threatening hypovolemic shock after thoracic surgery associated with a non-functioning chest tube.

We report a case of a massive haemothorax following bilateral surgical resection of apical bullae. Occult bleeding was not recognized until the onset of a life-threatening circulatory collapse associated with metabolic acidosis and a fall in haemoglobin level. Using a thoracotomy, large amounts of blood were evacuated from the thoracic cavity and bleeding originating from ruptured pleural adhesion was easily controlled. Thrombotic material with talc particles was found to obstruct the 19-French 4-channel Blake drain. Although this new silastic Blake tube has been recommended in cardiac surgical patients, extending its indication in thoracic surgery, particularly when talc pleurodesis is used, should be questioned given the enhanced postoperative prothrombotic state and risk of drain obstruction. In conclusion, caution should be exercised when new small-sized material is introduced in clinical practice, especially after talc pleurodesis following thoracic surgery.

Adult↗