Hypoxia-regulated carbonic anhydrase IX expression is associated with poor survival in patients with invasive breast cancer

Tumour hypoxia is a microenvironmental factor related to poor response to radiation, chemotherapy, genetic instability, selection for resistance to apoptosis, and increased risk of invasion and metastasis. Hypoxia-regulated carbonic anhydrase IX (CA IX) has been studied in various tumour sites and its expression has been correlated with the clinical outcome. The purpose of this study was to investigate the correlation of CA IX expression with outcome in patients with invasive breast cancer. We conducted a retrospective study examining the effects of carbonic anhydrase IX (CA IX) on survival in patients with breast cancer. To facilitate the screening of multiple tissue blocks from each patient, tissue microarrays were prepared containing between two and five representative samples of tumour per patient. Immunohistochemistry was used to examine expression of CA IX in patients with breast cancer. The study includes a cohort of 144 unselected patients with early invasive breast cancer who underwent surgery, and had CA IX expression and follow-up data available for analysis. At the time of analysis, there were 28 deaths and median follow-up of 48 months with 96% of patients having at least 2 years of follow-up. CA IX was negative for 107 patients (17 deaths) and positive for 37 patients (11 deaths). Kaplan-Meier survival curves show that survival was superior in the CA IX-negative group with a 2-year survival of 97% for negatives and 83% for positives (log-rank test P=0.01). Allowing for potential prognostic variables in a Cox regression analysis, CA IX remained a significant independent predictor of survival (P=0.035). This study showed in both univariate and multivariate analysis that survival is significantly inferior in patients with tumour expressing CA IX. Prospective studies are underway to investigate this correlation in clinical trial setting.     

Post-operative use of remoulding orthoses following cranial vault remodelling: a case series

The use of external orthoses following surgical cranial vault remodelling in infants with craniosynostosis was first described in the 1980s. While a few preliminary reports have been published on its use, there are no reports outlining specific orthotic considerations. The purpose of this paper is to present the orthotic community with an introduction to the various craniosynostoses, the resultant cranial morphologies, and specific orthotic considerations associated with these morphologies, including trigocephaly, frontal plagiocephly, brachycephaly, scapholocephaly, and occipital plagiocephaly. For each presentation, guidelines are presented as to where the cranial remoulding orthosis should maintain contact, thereby discouraging cranial growth, and where the voids should be established and maintained to allow for corrective cranial growth. Principles are supported by photographs of representative cases.     

Acute pancreatitis as a complication of percutaneous mechanical thrombectomy

Percutaneous mechanical thrombectomy can be an effective procedure performed with low morbidity. We have observed clinically significant pancreatitis after successful clot extraction by percutaneous thrombectomy. Pancreatitis developed postoperatively in four patients who underwent thrombectomy at our hospital. Each patient experienced abdominal symptoms with serologic and radiographic evidence of pancreatitis 相似文献   

Treating schizophrenia symptoms with an alpha7 nicotinic agonist, from mice to men

Current antipsychotic treatments fail to fully address the range of symptoms of schizophrenia, particularly with respect to social and occupational dysfunctions. Recent work has highlighted the role of nicotinie in both cognitive and attentional deficits as well as deficient processing of repetitive sensory information. The predilection for schizophrenia patients to be extremely heavy cigarette smokers may be related to their attempt to compensate for a reduction in hippocampal alpha7 nicotinic cholinergic receptors by delivering exogenous ligand to the remaining receptors. Studies in rodent models of both learning and memory deficits and deficits in sensory inhibition have confirmed a role for the alpha7 subtype of the nicotinic cholinergic receptor in these processes. Rodent studies also demonstrated the efficacy of a selective partial alpha7 nicotinic agonist, DMXBA, to improve these deficits. Subsequent human clinical trials demonstrated improved sensory inhibition in 12 schizophrenia patients and showed improvement in several subtests of the RBANS learning and memory assessment instrument. These data suggest that therapeutic agents selected for alpha7 nicotinic activity may have utility in treating certain symptoms of schizophrenia.     

The use of simple dynamic mucosal models and confocal microscopy for the evaluation of lyophilised nasal formulations

A range of methods is reported in the literature for assessing hydration and adhesion parameters in the performance of nasal bioadhesive formulations; however, these tests do not always represent the dynamic conditions in the nasal cavity. Lyophilised formulations intended for nasal administration were evaluated using in-vitro tests designed in an attempt to mimic relevant processes in the nasal cavity, and intended to discriminate between different formulations. Initial investigative studies using scanning electron microscopy revealed that the lyophilisate had a highly porous internal structure, expected to provide an ideal porous pathway for re-hydration. Vapour sorption analysis demonstrated substantial weight gain of the lyophilisates on exposure to 95% relative humidity, ranging from 38% to 66%. Agar was used as a synthetic mucosal model designed to provide a standardised quantity of water available for rehydration of the formulations in in-vitro tests. A dynamic adhesion test and a texture analyser sliding test were designed to quantify different aspects of the spreading and adhesion of the hydrating formulations on the synthetic mucosal surface. Examination of the lyophilised formulations using confocal microscopy allowed visualisation and quantification of the initial rate of water ingress into the lyophilisates, which was found to consist of an initial rapid phase, followed by a slower steady-state phase. The results demonstrated that the use of a combination of methods representing the dynamic conditions of the nasal cavity is advisable in order to evaluate a formulation fully and to avoid misleading conclusions.     

Uniform distribution of skin-temperature increase after different regional-anesthesia techniques of the lower extremity

BACKGROUND AND OBJECTIVES: Skin-temperature increase is a reliable but late indicator of success during regional-anesthesia techniques. The goal of this study is to determine the distribution of skin-temperature changes during different regional techniques. Does skin temperature increase in the whole area innervated by the blocked neural structures or only in certain regions within this area with the capability to react preferentially to sympathetic block (i.e., vessel-rich skin)? Although onset time may vary between different regional-anesthetic techniques, we hypothesized that the distribution of skin warming is equal. METHODS: Skin temperature was assessed continuously by infrared thermography in 24 patients who received either combined femoral-nerve and sciatic-nerve block, epidural anesthesia, or spinal anesthesia. RESULTS: Apart from differences in time of onset, no differential spatial distribution of skin-temperature changes could be detected. The earliest and greatest rise of skin temperature occurred at the great toe (10.6 degrees C +/- 0.4 degrees C), became smaller proximally, and was negligible above the ankles, irrespective of the type and extent of block. Video-thermography revealed that cold blood flows through subcutaneous veins immediately after onset of sympathetic block and initially decreases skin temperature (0.6 degrees C +/- 0.3 degrees C) during onset of spinal anesthesia. CONCLUSION: Irrespective of the applied regional-anesthetic technique, skin-temperature changes are more pronounced distally. Thermography prevents false measurements of skin temperature above subcutaneous veins and displays flow of cold blood as the mechanism of initial skin-temperature drop after regional anesthesia. Measurements of skin-temperature increase cannot be used to evaluate the extent of analgesia or sympathetic block.     

Cortical somatosensory-evoked potentials during spine surgery in patients with neuromuscular and idiopathic scoliosis under propofol-remifentanil anaesthesia

BACKGROUND: Intraoperative monitoring of the spinal cord via cortical somatosensory-evokedpotentials (SSEP) is a routine during spinal surgery. However,especially in neuromuscular scoliosis, the reliability of corticalSSEP has been questioned. Therefore, we compared the feasibilityof cortical SSEP in idiopathic and neuromuscular scoliosis usinganaesthetics known to have only minimal effect on SSEP recordings. METHODS: Total intravenous anaesthesia with propofol and remifentanilas continuous infusion was standardized for all the patients.Median and tibial nerve cortical SSEP were monitored in 54 patientswho underwent surgery for spinal deformity. Twenty-seven hadidiopathic scoliosis and 27 had neuromuscular scoliosis. Theportion of reproducible results and intraoperative changes werecompared between the groups. RESULTS: In both groups, cortical SSEP could be monitored with sufficientreliability. Only in two patients with idiopathic and four patientswith neuromuscular scoliosis no reproducible traces could beobtained. The amplitudes in patients with neuromuscular scoliosiswere lower than in those with idiopathic scoliosis, but notstatistically significant. There were no postoperative neurologicaldeficits. The number of false positive and true positive didnot differ between the groups. CONCLUSIONS: Assessment of cortical SSEP during spine surgery was equallyeffective and reliable in patients with neuromuscular scoliosisand in patients with idiopathic scoliosis, possibly as a resultof propofol–remifentanil anaesthesia.