Steroid premedication markedly reduces liver and bone marrow toxicity of trabectedin in advanced sarcoma

Trabectedin is a marine-derived cytoxic alkaloid which has shown promising antitumour activity in a variety of human malignancies including sarcoma. Fifty-four patients with advanced sarcoma (age 43 yrs, range 18-70), all pretreated with prior chemotherapy, were enrolled on a named individual basis for treatment with trabectedin. Diagnosis was adult soft tissue sarcoma (STS) in 46 patients, Ewing's family tumour (EFT) in 4, and osteosarcoma (OS) in 4. The initial 23 patients (total number of courses administered: 68) did not receive premedication prior to trabectedin, while the other 31 patients (total number of courses administered: 134) received premedication with dexamethasone 4 mg po bid 24 hours before therapy. Incidence of toxicity (grade 3-4), expressed as percentage of courses, was as follows: in patients without dexamethasone, elevation of transaminases 34%, neutropenia 24% and thrombocytopenia 25%; in patients with prior dexamethasone, elevation of transaminases 2%, neutropenia 2% and no thrombocytopenia. The median received dose intensity of trabectedin was superimposable in the two groups (404 microg and 400 microg per week, respectively), as well as progression-free survival (19% at 6 months). Among STS patients, 9% had objective responses. In this unselected patient series, premedication with dexamethasone strongly reduced drug-induced hepatotoxicity and myelosuppression.     

The prevention of adhesion formation by nonsteroidal antiinflammatory drugs: an animal study comparing ibuprofen and indomethacin

The efficacy of two nonsteroidal antiinflammatory drugs, ibuprofen and indomethacin, in the prevention of postoperative adhesions was examined. Thirty-three guinea pigs were randomly divided into three groups: a control group (n = 11), an ibuprofen group (n = 11), and an indomethacin group (n = 11). All of the animals received standardized injuries, and adhesions were graded 4 weeks later. Both treatment groups were found to have significantly fewer (P less than 0.01) adhesions when compared with the control group with no difference among the two treatment groups. It is concluded that ibuprofen and indomethacin are equally effective in reducing postoperative adhesions.     

Correlation of optical coherence tomography pattern and visual recovery after vitrectomy with silicone oil for retinal detachment

PURPOSE: To assess prospectively the features of the macular surface in silicone oil-filled eyes after surgery by analyzing whether silicone oil affects optical coherence tomography (OCT) measurements and their reproducibility and whether a statistical correlation exists between postoperative best-corrected visual acuity (BCVA) and foveal thickness measured by OCT. METHODS: Twenty eyes of 20 patients underwent vitrectomy with silicone oil tamponade for retinal detachment. After vitrectomy, complete ophthalmic examination including determination of BCVA and OCT was performed to quantify the visual recovery and the foveal thickness. RESULTS: Ophthalmoscopy revealed that the retina appeared to be reattached in all 20 eyes at 3 months after surgery. BCVA ranged from 0.4 logMAR to 1.7 logMAR, and foveal thickness ranged from 80 microm to 500 microm. Postoperative foveal thickness and BCVA had a strong correlation (r = 0.93; P = 0.003). CONCLUSION: The presence of silicone oil in the vitreous chamber does not change the reproducibility of OCT measurements of foveal thickness (coefficient of reproducibility, 1.48%). This study showed high statistical correlation between BCVA and foveal thickness. Therefore, postoperative BCVA is affected by postoperative foveal thickness, and visual improvement is limited in eyes with increased or decreased foveal thickness.     

Evaluation of danazol influence upon the uterus using scanning electron microscopic morphometric and biochemical analyses

A study using a Sprague-Dawley rat model was designed to correlate morphologic and intracellular steroid receptor alteration with danazol therapy. One uterine horn was removed for cytoplasmic estrogen receptor analysis following four to eight days of danazol therapy. This was followed by intra-aortic injection of buffered phosphate solution and 3 per cent glutaraldehyde. The remaining uterine horn was removed for scanning electron microscopic and morphometric analysis of light microscopic changes. After four days of treatment, there was an increase in the nuclear to cytoplasmic ratio compared with that of the control tissue. Vaginal smears on the eighth day of danazol exposure indicated that the rats had entered a noncycling estrus state, and there was a significant increase in the estrogen-specific binding capacity of the endometrial cells. Scanning electron microscopy showed a distinct decrease in endometrial folds, microvilli and glandular openings, which suggests a decline in secretory activity in the danazol-treated group. Thus, danazol induced measurable changes in the estrogen binding capacity of endometrial cells, and these changes correlated with certain morphologic alterations in the endometrial lining.     

Amino acid immunoreactivity in normal human retina and after brachytherapy

We localised amino acids in the mid‐peripheral aged human retina and a retina that had undergone radiation treatment 10 years earlier. The distribution pattern of glutamate, γ‐amino butyric acid (GABA), glycine, glutamine and taurine, reflected patterns established in the primate retina. The retina that had undergone radiation exposure displayed both anatomical and neurochemical remodelling. The proximal retina comprised around 40 to 45 per cent of the total retina and neuronal kinesis and aberrant neuronal projections were also present. Amino acid neurochemistry was strikingly different with Müller cells displaying GABA loading, glycinergic neurons displaced and displaying a very high level of glycine labelling. We conclude that radiation exposure triggered these changes in the human retina and likely reflects general remodelling of structure and function following ischaemic damage to endothelial cells.     

Canadian guidelines for training in adult perioperative transesophageal echocardiography. Recommendations of the Cardiovascular Section of the Canadian Anesthesiologists' Society and the Canadian Society of Echocardiography

PURPOSE: To establish Canadian guidelines for training in adult perioperative transesophageal echocardiography (TEE). METHODS: Guidelines were established by the Canadian Perioperative Echocardiography Group with the support of the cardiovascular section of the Canadian Anesthesiologists' Society in conjunction with the Canadian Society of Echocardiography. Guidelines for training in echocardiography by the American Society of Echocardiography, the American College of Cardiology and the Society of Cardiovascular Anesthesiologists were reviewed, modified and expanded to produce the 2003 Quebec expert consensus for training in perioperative echocardiography. The Quebec expert consensus and the 2005 guidelines for the provision of echocardiography in Canada formed the basis of the Canadian training guidelines in adult perioperative TEE. RESULTS: Basic, advanced and director levels of expertise were identified. The total number of echocardiographic examinations to achieve each level of expertise remains unchanged from the 2002 American Society of Echocardiography and the Society of Cardiovascular Anesthesiologists guidelines. The increased proportion of examinations personally performed at basic and advanced levels, as well as the level of autonomy at the basic level suggested by the Quebec expert consensus are retained. These examinations may be performed in a perioperative setting and are not limited to intraoperative TEE. Training 'on-the-job', the role of the perioperative TEE examination, the requirements for maintenance of competence and the duration of training are also discussed for each level of training. The components of a TEE report and comprehensive TEE examination are also outlined. CONCLUSION: The Canadian guidelines for training in adult perioperative TEE reflect the unique Canadian practice profile in perioperative TEE and address the training requirements to obtain expertise in this field.