Surgical sperm retrieval and intracytoplasmic sperm injection as treatment of obstructive azoospermia

Male genital tract obstructions may result from infections, previous inguinal and scrotal surgery (vasectomy) and congenital bilateral absence of the vas deferens (CBAVD). Microsurgery can sometimes be successful in treating the obstruction. In other cases and in cases of failed surgical intervention, the patient can be treated by microsurgical or percutaneous epididymal sperm aspiration (MESA, PESA) or testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). We present the results of 39 ICSI procedures for obstructive azoospermia in 24 couples. The aetiology of the obstruction was failed microsurgery in 11 patients, CBAVD in nine and genital infections in four. Sperm retrieval was accomplished via MESA in four cases, PESA in 18 cases and via TESE in 11 cases. TESE was only applied when PESA failed to produce enough spermatozoa for simultaneous ICSI. In six patients, the ICSI procedure was performed with cryopreserved spermatozoa after an initial PESA procedure. Fertilization occurred in 47% of the metaphase II oocytes; embryo transfer was performed in 92% of procedures and resulted in a clinical pregnancy in 13/39 procedures. Ongoing pregnancy was achieved in 10/39 procedures. One pregnancy was terminated early after prenatal investigation showed a cytogenetic abnormality (47,XX+18, Edwards syndrome). The other nine pregnancies resulted in the live birth of 10 children, without any congenital abnormalities. Epididymal and testicular retrieved spermatozoa were successfully used for ICSI to treat obstructive azoospermia, and resulted in an ongoing pregnancy in 10 of 24 couples (41.6%) after 39 ICSI procedures, a success rate of 25.6% per treatment cycle and of 27.7% per embryo transfer.      

Active detachment involves inhibition of cell-matrix contacts of malignant melanoma cells by secretion of melanoma inhibitory activity

Melanoma inhibitory activity (MIA) has been identified as a small protein secreted from malignant melanoma cells. Recent results revealed a direct interaction of MIA and epitopes within extracellular matrix proteins including fibronectin. The aim of this study was to analyze functional consequences mediated by this interaction. Here we show that MIA interferes specifically with attachment of melanoma cells to fibronectin, a phenomenon we refer to as active detachment. Antibodies inhibiting binding of alpha4beta1 and alpha5beta1 integrins to fibronectin cross-react specifically with MIA, suggesting that MIA shares significant structural homology with the binding pockets of these integrins and thereby masks the respective epitopes on extracellular matrix molecules. Several peptides derived from fibronectin and from a phage display screening were tested with respect to a potential MIA-inhibitory effect. In vitro tests identified two peptides affecting MIA function; both inhibited growth of melanoma metastases in vivo. In summary, we conclude that MIA may play a role in tumor progression and spread of malignant melanomas via mediating active detachment of cells from extracellular matrix molecules within their local milieu. Further, our results suggest that inhibiting MIA functions in vivo may provide a novel therapeutic strategy for metastatic melanoma disease.     

Measurement of leukocyte motility and chemotaxis parameters with the Millipore filter assay

Although in vitro assays have been widely used to study leukocyte chemotactic migration, finding the best way to quantitate these assays has proven to be an elusive goal. Investigators have usually resorted to reporting quantities such as the leading front distance, total migrating cells or number of cells past a given distance from their starting point. While these measures may often provide a valid comparison of cell migration under specific assay conditions, they also reflect physical characteristics of the assay that are irrelevant to the basic phenomenon of interest; thus, typical quantities measured in the assay are not useful for comparison between different systems or for correlation with in vivo performance. Recently, however, Tranquillo et al. (1988) demonstrated the utility of an analysis of the under-agarose assay in which the density profile of migrating cells is characterized in terms of two parameters: the random motility coefficient, mu, and the chemotaxis coefficient, chi. These parameters do reflect intrinsic cell movement independently of extraneous physical conditions. The analysis relies primarily on matching theoretical cell density profiles, calculated from a mathematical model in which mu and chi appear, to cell density profiles measured experimentally in the assay. In this paper, we extend the work of Tranquillo et al. to show that the same model can be applied successfully to the Millipore filter assay. In addition, we present measured values of mu and chi for rabbit polymorphonuclear leukocytes (PMNs) in response to, and as a function of the concentration of, the peptide attractant formyl-norleucyl-leucyl-phenylalanine (FNLLP). We also examine the relationship between results obtained for the filter assay and the under-agarose assay and consider the mechanistic basis of the parameters mu and chi.     

Quantitative examination of isometric tongue protrusion forces in children with oro‐facial dysfunctions or myofunctional disorders

Oro‐facial dysfunctions (OFD) or oro‐facial myofunctional disorders in children lead to severe problems in teeth and jaw position, articulation, chewing and swallowing. The forces of the tongue, the central muscle for articulation, chewing and swallowing are focused on in several studies. In this examination, isometric tongue protrusion forces (TPF) of children with OFD and controls were compared. Thirty participants with OFD and 30 controls were presented a target force level as a straight line on a monitor that they were supposed to match by generating an isometric tongue force for different target levels (0.25 N and 0.5 N). Correlations of the severity of OFD (symptom score) with the capacities of the TPF 0.25 N and 0.5 N were calculated. Statistical differences were obvious in TPF variability and the accuracy, depending on the weight. Tongue contact time, expressed as per cent (TCT, total contact: 100%), was significantly lower in children with OFD (P = .005). Mean and median TPF was not different between groups. The predictive value of TPF for OFD revealed a level of 58.6% for TPF 0.25 N and 74.5% for TPF 0.5 N. Correlations of the severity of OFD were seen for some parameters. Subjects with OFD show significantly lower competencies in accuracy and endurance of tongue protrusion forces. This may have a high impact on phenotyping children with OFD and influence therapeutical approaches.     

Resilience in families with a member with chronic pain: a mixed methods study

Aims and objective. To measure and explore between 2007–2010 measure and explore the nature of family resilience in the context of families with a member with chronic pain. Background. Chronic pain impacts on the entire family. The literature suggests that it is possible to strengthen resilience in individuals with chronic conditions, but little is known about the impact of chronic pain on family resilience. Design. A explanatory sequential mixed method study was undertaken. Methods. In the initial quantitative phase, assessment measures were administered using the Connor‐Davidson Resilience Scale, Family Impact of Pain Scale, Medical Outcomes Study Short Form 36 and Medical Outcomes Study Social Support Survey. Data were collected and analysed from 31 family cases (n = 67 participants). In the second, qualitative phase, follow‐up semi‐structured interviews were undertaken with 10 families to help explain the quantitative results. Results. The impact of pain on the family was high overall, but the perceived impact was greater for the person with pain. Resilience scores were above average for both the person with pain and other family members. However, the person with pain scored lower on the resilience scale than other members of the family. The families scored high for social support overall, while the person with pain perceived they had greater support than their family members. Conclusions. Identifying the strengths or resilient properties inherent in families and using those strengths in the planning and implementation of care, especially of chronic conditions such as chronic pain, is pivotal to quality health outcomes. Relevance to clinical practice.  It is important that nurses and healthcare professionals include family members when planning and delivering care for persons with chronic pain. Identification of strengths within families can help tailor nursing interventions to meet family needs.