PDT in clinics: indications, results, and markets.

Photodynamic therapy (PDT) is based on the selective light activation of an exogenously given drug to patients. PDT acts mainly on cell membranes either of neovascular endothelial cells or of cancer cells leading to cancer cell death. Six drugs are now marketed based on clinical assays in various indications, which showed a clear cost efficiency as compared to other classical procedures. PDT is easy to handle and can be performed in medical installations fitting the conditions of health care in developing countries. Its cost effectiveness could represent an appropriate solution to the increasing number of cancers of various origin. However despite all the clinical results now available, PDT development remains slow. The reasons for this situation include cost of development, intellectual property, and competition between pharmaceutical companies.     

Particulate endocytosis mediates biological responses of human mesenchymal stem cells to titanium wear debris.

Continual loading and articulation cycles undergone by metallic (e.g., titanium) alloy arthroplasty prostheses lead to liberation of a large number of metallic debris particulates, which have long been implicated as a primary cause of periprosthetic osteolysis and postarthroplasty aseptic implant loosening. Long-term stability of total joint replacement prostheses relies on proper integration between implant biomaterial and osseous tissue, and factors that interfere with this integration are likely to cause osteolysis. Because multipotent mesenchymal stem cells (MSCs) located adjacent to the implant have an osteoprogenitor function and are critical contributors to osseous tissue integrity, when their functions or activities are compromised, osteolysis will most likely occur. To date, it is not certain or sufficiently confirmed whether MSCs endocytose titanium particles, and if so, whether particulate endocytosis has any effect on cellular responses to wear debris. This study seeks to clarify the phenomenon of titanium endocytosis by human MSCs (hMSCs), and investigates the influence of endocytosis on their activities. hMSCs incubated with commercially pure titanium particles exhibited internalized particles, as observed by scanning electron microscopy and confocal laser scanning microscopy, with time-dependent reduction in the number of extracellular particles. Particulate endocytosis was associated with reduced rates of cellular proliferation and cell-substrate adhesion, suppressed osteogenic differentiation, and increased rate of apoptosis. These cellular effects of exposure to titanium particles were reduced when endocytosis was inhibited by treatment with cytochalasin D, and no significant effect was seen when hMSCs were treated only with conditioned medium obtained from particulate-treated cells. These findings strongly suggest that the biological responses of hMSCs to wear debris are triggered primarily by the direct endocytosis of titanium particulates, and not mediated by secreted soluble factors. In this manner, therapeutical approaches that suppress particle endocytosis could reduce the bioreactivity of hMSCs to particulates, and enhance long-term orthopedic implant prognosis by minimizing wear-debris periprosthethic osteolysis.     

Perception and use of the results of patient satisfaction surveys by care providers in a French teaching hospital.

OBJECTIVE: . The aim of this study was to assess clinical staff's opinions on the results of in-patient satisfaction surveys and their use within the quality improvement process. SETTING: The institution is a 2200-bed teaching hospital of tertiary health care employing 8000 professionals. Patient satisfaction surveys are carried out each year using a validated questionnaire mailed to a random sample of patients. The specific results of each department are sent to the medical and paramedical managers. METHODS: We conducted a questionnaire survey on 500 care providers randomly selected in every medical and surgical department. RESULTS: A total of 261 questionnaires were returned and analysed. Overall, 94% of responders had a favourable opinion of the patient satisfaction surveys. They considered that the patient was able to judge hospital service quality, especially in its relational, organizational, and environmental dimensions. The specific results for the department were less well known than the overall hospital results (60 versus 76%). These results were formally discussed in the department according to 40% of responders; 40% declared that these data resulted in improvement actions and considered that they led to modifications in their behaviour with patients. CONCLUSIONS: Despite a declared interest in satisfaction surveys, the results remain underused by hospital staff and insufficiently discussed within teams.     

Ventilation imaging of the lung: Comparison of hyperpolarized helium-3 MR imaging with Xe-133 scintigraphy

RATIONALE AND OBJECTIVES: To compare hyperpolarized helium-3 (HHe) magnetic resonance imaging (MRI) of the lung with standard Xe-133 lung ventilation scintigraphy. MATERIALS AND METHODS: We performed a retrospective review of 15 subjects who underwent HHe MRI and Xe-133 lung ventilation imaging. Coronal MRI sections were acquired after a single inhalation of HHe gas, and standard posterior planar lung ventilation scintigraphy was performed during continuous breathing of Xe-133 gas. The first breath scintigram of each patient was compared with a composite MR image composed of the sum of the individual MR images and with the individual helium-3 MR images. Ventilation defects on the two imaging modalities were compared for size, conspicuity, and concordance in presence and location. Assessment was done separately for each of four lung quadrants. RESULTS: Comparing the composite HHe MR images with Xe-133 scintigraphy, ventilation defect size, conspicuity and concordance were the same in 67% (40/60), 63% (38/60), and 62% (37/60) quadrants, respectively. Comparing the individual HHe MR image sections with the Xe-133 ventilation scan, there was concordance between the ventilation defects in 27% (16/60) of quadrants. More defects were identified on the individual HHe MR images in 62% (37/60) of quadrants. CONCLUSION: There was good agreement between composite HHe MR image and first breath Xe-133 scintigraphic images, supporting the widely held assumption that HHe MRI likely depicts first breath lung ventilation.     

Lactation-induced plasticity in the supraoptic nucleus augments axodendritic and axosomatic GABAergic and glutamatergic synapses: an ultrastructural analysis using the disector method

The disector, an unbiased stereological method for evaluation of synaptic densities, was used to analyse putative GABA and glutamate innervations of the supraoptic nucleus of virgin and lactating rats. The analysis was performed on ultrathin sections labelled for either of the amino acids with a postembedding immunogold technique. Our observations showed that the volume of the nucleus increased by 40% in lactating animals, an increase due to a significant enlargment of dendritic and somatic, but not vascular, volumes. Nevertheless, values of overall synaptic densities in the whole nucleus remained as high as those in virgin rats (37–40×10⁶ synapses/mm³). About 45% of all synapses were immunoreactive for GABA and 25% for glutamate; there were twice as many GABA- and glutamate-positive synapses on dendrites as on somata. When we estimated synaptic densities in relation to the neuropil (by subtracting the proportion of sampled areas occupied by somatic profiles), we found a significant increase in synaptic density in lactating animals. This affected axodendritic as well as axosomatic synapses, immunopositive and immunonegative for GABA or glutamate. The disector also allowed us to determine that the number of synapses from terminals making contacts on several somata and/or dendrites simultaneously constituted about 9% of all synapses in virgin rats, a proportion which more than doubled in lactating rats. About 50% were immunopositive for GABA and 30% for glutamate.

Our data offer further evidence of physiologically-linked structural synaptic plasticity in the supraoptic nucleus and clearly demonstrate that it affects both inhibitory and excitatory inputs on dendrites, as well as on somata, throughout the nucleus.     

Predicting occupational performance: handwriting versus keyboarding.

PURPOSE: To determine whether there is a correlation between handwriting and keyboarding speed and accuracy, and whether handwriting and keyboarding share common underlying components. METHODS: Sixty-three typically developing 5th-grade students attended a series of 15 keyboarding lessons for a total of 5 hours. Prior to the lessons, cognitive, sensory, and motor skills related to handwriting were evaluated. Prior to and following the lessons keyboarding and handwriting accuracy and speed were also tested. Correlations were employed to examine relationships between handwriting and keyboarding skills and multiple regression analyses were used to examine the contribution of performance components to handwriting and keyboarding performance. RESULTS: Following keyboarding instruction, a significant correlation was found between handwriting and keyboarding speed, but not in accuracy of these tasks. Similarly, some of the specific tests measuring tactile and oculo-motor functions were found to be related to both handwriting and keyboarding speed, yet accuracy of these tasks did not share common underlying components. CONCLUSIONS: It appears that handwriting and keyboarding accuracy may entail different skills, suggesting that keyboarding may be a potential alternative writing tool for students with handwriting difficulties. It also appears that when students write slowly, handwriting speed should be considered prior to recommending keyboarding for these students. Additional research is required to further support these findings.     

The Glutamatergic Innervation of Oxytocin- and Vasopressin-secreting Neurons in the Rat Supraoptic Nucleus and its Contribution to Lactation-induced Synaptic Plasticity

The present ultrastructural study analysed the distribution of glutamatergic synapses on oxytocin- and vasopressin-secreting neurons in the rat supraoptic nucleus (SON) after post-embedding immunogold labelling for glutamate and GABA, oxytocin or vasopressin. About 20% of SON axo—somatic synapses were enriched in glutamate immunoreactivity, visible over synaptic-like vesicles, mitochondria and synaptic densities. Double labelling for glutamate and GABA showed that putative glutamatergic terminals were distinct from GABAergic terminals. In ultrathin sections stained for glutamate and either oxytocin or vasopressin, the proportion of glutamatergic synapses was similar on oxytocinergic and vasopressinergic somata in virgin rats under basal conditions of peptide release as well as in lactating rats, in which oxytocin secretion is enhanced. Cross-sectional soma areas were significantly increased in lactating rats: oxytocinergic profiles were, on average, ˜40% larger than in virgin rats. However, the incidence of axo—somatic glutamatergic synapses (assessed as mean number of synapses per 100 μm of plasmalemma or proportion of somatic surface apposed to synaptic active zones) did not diminish, indicating that there was a compensatory increase of synapses during lactation. Also, we found an increase in the number of glutamatergic terminals making synaptic contact simultaneously onto two or more oxytocinergic elements in the same plane of section. Our observations therefore indicate that SON oxytocinergic and vasopressinergic neurons are innervated to a similar extent by a relatively large proportion of glutamatergic synapses. They reveal, moreover, that glutamatergic afferents participate in the lactation-induced synaptic plasticity of the oxytocinergic system.