Analgesic effects of botulinum toxin A: a randomized, placebo-controlled clinical trial

Postoperative pain in children with spastic cerebral palsy (CP) is often attributed to muscle spasm and is difficult to manage using opiates and benzodiazepines. Adductor-release surgery to treat or prevent hip dislocation in children with spastic CP is frequently performed and is often accompanied by severe postoperative pain and spasm. A double-blinded, randomized, placebo-controlled clinical trial of 16 patients (mean age 4.7 years) with a mainly spastic type of CP (either diplegic or quadriplegic in distribution) was used to test the hypothesis that a significant proportion of postoperative pain is secondary to muscle spasm and, therefore, might be reduced by a preoperative chemodenervation of the target surgical muscle by intramuscular injection of botulinum toxin A (BTX/A). Compared with the placebo, BTX/A was found to be associated with a reduction in mean pain scores of 74% (P<0.003), a reduction in mean analgesic requirements of approximately 50% (P<0.005), and a reduction in mean length of hospital admission of 33% (P<0.003). It was concluded that an important component of postoperative pain in the patient population is due to muscle spasm and this can be managed effectively by preoperative injection with BTX/A. These findings may have implications for the management of pain secondary to muscle spasm in other clinical settings.     

Human brain thioltransferase: constitutive expression and localization by fluorescence in situ hybridization

Thioltransferase (glutaredoxin) is a member of the family of thiol-disulfide oxido-reductases that maintain the sulfhydryl homeostasis in cells by catalyzing thiol-disulfide interchange reactions. One of the major consequences of oxidative stress in brain is formation of protein-glutathione mixed disulfide (through oxidation of protein thiols) which can be reversed by thioltransferase during recovery of brain from oxidative stress. Here we have visualized the location of thioltransferase in brain regions from seven human tissues obtained at autopsy. Constitutively expressed thioltransferase activity was detectable in all human brains examined although inter-individual variations were seen. The enzyme activity was significantly higher in hippocampus and cerebellum as compared to other regions. Constitutive expression of thioltransferase mRNA was detectable by Northern blot analysis. Localization of thioltransferase mRNA by fluorescence in situ hybridization revealed its presence predominantly in neurons in the cerebral cortex, Purkinje and granule cell layers of the cerebellum, granule cell layer of the dentate gyrus and in the pyramidal neurons of CA1, CA2 and CA3 subfields of hippocampus. These discrete neuronal concentrations of thioltransferase would be consistent with an essential role in modulating recovery of protein thiols from mixed disulfides formed during oxidative stress.     

Three-dimensional video-assisted thoracoscopic pericardiectomy

Video-assisted thoracic surgery has proven to be safe and effective for the diagnosis and management of pericardial disease. Three-dimensional (3-D) video imaging technology has been developed to allow the laparoscopic surgeon more precision and efficiency in advanced laparoscopic cases. This case report describes the marriage of 3-D video imaging and thoracoscopy that allowed performance of a technically difficult pericardiectomy without incident. Our aim is to describe the use of state-of-the-art 3-D video imaging to allow success in difficult cases.     

Expression of integrin adhesion molecules in normal ovary and epithelial ovarian tumors

The metastatic potential of a solid tumor is dependent upon its ability to interact with the extracellular matrix. The integrin superfamily is a group of proteins that are fundamental in such interactions and play a major role in cell-cell and cell-matrix adhesion. Localization of the integrin proteins was performed in normal ovary, primary epithelial ovarian tumors and metastatic tumor cells in ascitic samples. Expression of α₁, α₃, α₆ and β₄ was observed on normal ovarian epithelium with variable expression of α₅. Loss of α₁ expression by malignant cells in the primary tumors was noted. β₄, a component of the laminin receptor which was strongly expressed by both normal ovary and solid tumor, was absent from the ascitic tumor cells in the majority of cases. There was an associated loss of α₆ expression, indicating a deficiency of hemidesmosomes in the ascitic tumor cells. This alteration of integrin expression by metastatic malignant epithelial ovarian tumor cells may therefore represent one important mechanism by which metastatic disease occurs.     

THE EFFECT OF MULTIPLE EMBOLI OF THE CAPILLARIES AND ARTERIOLES OF ONE LUNG

1. Injection of a suspension of potato starch cells into the left branch of the pulmonary artery, in quantity sufficient ordinarily to give rise to markedly accelerated respirations, resulted in no change in respiratory rate. 2. A method for injecting substances into the pulmonary artery or its branches without interfering with the blood flow to the lungs has been described. 3. Injection of similar material into one lung when the other is excluded from the circulation either by ligation or by temporary clamping does give rise to rapid and shallow breathing (from a rate of 10 to 15 per minute to one of 60 or over) identical in character to that brought about by introducing emboli into both lungs. 4. A method for clamping and releasing the pulmonary artery or its branches in a dog breathing normally with closed thorax has been devised. This is described in detail in another paper. 5. After rapid breathing has been initiated by the effect of emboli lodged in the arterioles and capillaries of the right lung, reestablishing the circulation in the other lung by releasing the clamp on its artery may or may not restore the respiratory rate to its original, normal level. 6. This discrepancy in results has not been correlated with any difference in oxygen saturation of the arterial blood, or in carbon dioxide tension or pH of its plasma. 7. It is, however, believed to be related to the gross and microscopic anatomy of the lung of which the artery has been temporarily clamped. Photomicrographs are published, showing in one dog (No. 3), in which the respiratory rate returned to normal, a normal histological picture of the left lung, and in another dog (No. 4), in which the rate remained rapid after release of the clamp, a picture characterized by congestion and dilatation of arterioles and capillaries. 8. The fact that accelerated respirations result from emboli in the pulmonary capillaries and arterioles only after a certain quantity of material has been introduced, and the fact that emboli in one lung do not occasion accelerated respirations unless the circulation through the other lung is occluded or abnormal, leads us to the conclusion that the phenomenon is not an irritative stimulus due to foreign bodies, but is in some manner related to (a) diminution of the pulmonary vascular bed, (b) resistance to the blood flow through the lungs or (c) congestion or dilatation of the arterioles and capillaries of the lungs.     

Reductive metabolism of nitrofurantoin by rat lung and liver in vitro

In the present study, the metabolism of NF has been examined in detail in both rat lung and liver 9000 g supernatants using a specific radiometric HPLC assay. Over 92% of the total radioactivity chromatographed with authentic NF after incubations from either organ were carried out under oxygen for 60 min. Under anaerobic conditions, only 19% and 5% of the total unbound radioactivity corresponded to unchanged NF in lung and liver respectively. At least 4 metabolites were evident from the HPLC trace (M1, M2, M3, M4 according to increasing retention times). In the absence of oxygen, liver 9000 g supernatants generated 65% more M1 and 260% more M3 than did lung 9000 g supernatants, but the lung produced significantly more M4. Covalent binding to tissue macromolecules was similar in both tissues under oxygen but was 7 times greater in lung than in liver in the absence of oxygen (compared per unit protein). Neither piperonyl butoxide nor indomethacin affected NF metabolism. However, allopurinol almost completely inhibited the anaerobic and aerobic (superoxide generation measured by the rate of acetylated cytochrome c reduction) metabolism in the lung with little or no effect in the liver. The data indicate a quantitative difference in NF metabolism between the two tissues that may be related to the organ-selective toxicity of the drug.