Rapid growth of cartilage rudiments may generate perichondrial structures by mechanical induction.

Experimental and theoretical research suggest that mechanical stimuli may play a role in morphogenesis. We investigated whether theoretically predicted patterns of stress and strain generated during the growth of a skeletal condensation are similar to in vivo expression patterns of chondrogenic and osteogenic genes. The analysis showed that predicted patterns of compressive hydrostatic stress (pressure) correspond to the expression patterns of chondrogenic genes, and predicted patterns of tensile strain correspond to the expression patterns of osteogenic genes. Furthermore, the results of iterative application of the analysis suggest that stresses and strains generated by the growing condensation could promote the formation and refinement of stiff tissue surrounding the condensation, a prediction that is in agreement with an observed increase in collagen bundling surrounding the cartilage condensation, as indicated by picro-sirius red staining. These results are consistent with mechanical stimuli playing an inductive or maintenance role in the developing cartilage and associated perichondrium and bone collar. This theoretical analysis provides insight into the potential importance of mechanical stimuli during the growth of skeletogenic condensations.

Mechanical induction in limb morphogenesis: the role of growth-generated strains and pressures.

Morphogenesis is regulated by intrinsic factors within cells and by inductive signals transmitted through direct contact, diffusible molecules, and gap junctions. In addition, connected tissues growing at different rates necessarily generate complicated distributions of physical deformations (strains) and pressures. In this Perspective we present the hypothesis that growth-generated strains and pressures in developing tissues regulate morphogenesis throughout development. We propose that these local mechanical cues influence morphogenesis by: (1) modulating growth rates; (2) modulating tissue differentiation; (3) influencing the direction of growth; and (4) deforming tissues. It is in this context that we review concepts and experiments of cell signaling and gene expression in various mechanical environments. Tissue and organ culture experiments are interpreted in light of the developmental events associated with the growth of the limb buds and provide initial support for the presence and morphological importance of growth-generated strains and pressures. The concepts presented are used to suggest future lines of research that may give rise to a more integrated mechanobiological view of early embryonic musculoskeletal morphogenesis.

Continuous venovenous haemofiltration for the treatment of theophylline toxicity.

In patients with severe theophylline toxicity charcoal haemoperfusion is the recommended method for rapid reduction of serum theophylline levels. However, access to this technique is limited in most hospitals. This case report shows that continuous venovenous haemofiltration, a technique available in most hospitals, is an effective alternative to charcoal haemoperfusion.

Medical management of obstructive sleep apnea.

The last 20 years have seen remarkable gains in our understanding of the pathophysiology of sleep-disordered breathing. The rapid growth in both scientific and clinical knowledge has been fueled by the development of nonsurgical therapies for obstructive sleep apnea (OSA). These medical therapies have provided the avenue for public acceptance of the diagnosis and treatment of this common medical condition. However, medical therapy requires active patient participation, to achieve the desired outcomes of improved sleep continuity, daytime functioning, and quality of life. Conservative therapies, such as weight loss and patient positioning; and pharmacological therapies, have been disappointing. Positive pressure therapy has become the treatment of choice for the vast majority of OSA patients. Oral appliances offer an acceptable treatment alternative for select patients. Present research indicates that these mechanical approaches can produce significant decreases in the frequency and severity of sleep-disordered breathing and nocturnal oxyhemoglobin desaturation. Preliminary data from ongoing studies suggest that these interventions will reduce long-term morbidity and possibly mortality.

Comparison of the Wang 19-gauge and 22-gauge needles in the mediastinal staging of lung cancer.

Transbronchial needle aspiration (TBNA) offers the unique opportunity to pathologically stage patients with lung cancer at the time of diagnostic bronchoscopy. The purpose of this study was to compare the staging sensitivities of the Wang 22-gauge and 19-gauge needles. We studied 64 patients with bronchogenic carcinoma and mediastinal adenopathy. Before bronchoscopy each patient underwent chest CT. Three to four aspirates were obtained with each needle from endotracheal sites adjacent to paratracheal lymphadenopathy. In 47 patients malignant mediastinal adenopathy was confirmed by the 19-gauge needle. A total of 29 patients had malignant 22-gauge needle aspirates. Of the 64 patients, 9 had benign, reactive mediastinal lymph nodes. There were 20 patients in whom only the 19-gauge needle demonstrated malignancy and 2 patients with malignant 22-gauge needle aspirates as the sole identifier of paratracheal malignancy. As a staging tool, the 19-gauge needle was significantly more sensitive than the 22-gauge needle, 85.5 versus 52.7% (p = 0.0001). Overall, in 49 of 55 patients (89.1%) with malignant mediastinal lymphadenopathy paratracheal tumor was confirmed by TBNA. The 19-gauge TBNA staging of the mediastinum is an effective, safe, and cost-saving alternative to surgical mediastinal exploration that can be performed during initial diagnostic bronchoscopy.

The evaluation of mental health care transformation in the cities of Europe.

At the WHO International Conference 'Changing Mental Health Care in the Cities of Europe' an invitational workshop was organised for participants interested in evaluation research. This report of the workshop first summarises the activities of the Commission of European Communities working on the 'Evaluation of Comprehensive Care of the Mentally Ill'. Secondly current issues which arose in the discussions on problems of scientific evaluation of changing mental health care in Europe are described. Thirdly three particular research programmes are summarised especially focussing on research methodology.