The Martin Titanline arterial clamp. A new lightweight alternative

When haemostatic clamps are applied, evidence of injury at the site of clamp application may be seen when the clamp is removed. Rarely, the intima may be disrupted. When a new arterial clamp became available, a study was designed to compare the Martin Titanline arterial clamp (13-143-35, curved arterial clamp) with several other arterial clamps already in use. The Martin clamp is a modified pivot-point, preset-tension, spring-controlled arterial clamp. The closing pressures of several clamps were measured objectively. The injury produced when the clamps were applied to occlude the blood flow on the carotid artery of a dog was assessed by histological study of the excised segments of the arterial wall. Histological cross-sections were prepared from canine carotid artery which had been perfused for 1 h after the clamp had been applied for 1 h. Histological evidence of injury was limited to disruption of the intimal layer and compression of the medial layer. No significant difference between the amount of damage caused by the DeBakey, Satinsky or Martin clamp was identified. When compared to the other varieties of clamp listed above, the Martin clamp had a significantly lower closing pressure (304 g) compared with 580g (Bulldog), 580 g (Satinsky), and 686 g (DeBakey). The Martin clamp was easier to apply, did not obstruct the operative field as readily and had good clamp-retention characteristics throughout the procedure.     

Cell generation within human thymic subsets defined by selective expression of CD45 (T200) isoforms

Although the thymus is the source of all mature peripheral T lymphocytes, the majority of thymocytes die intrathymically. Until recently, there has been no phenotypic marker to allow definition of the generative thymocyte lineage, thereby distinguishing those thymocytes committed to death from those which will evenually give rise to thymic emigrants. We believe that expression of the high-molecular-mass isoforms (p190, p205, and/or p220) of the leukocyte common antigen (CD45) distinguishes the thymic generative lineage from the vast majority of thymocytes expressing the low-molecular-mass isoform (p180) of CD45 and committed to die within the thymus. The thymocytes defined by their lack of CD45 p180, the low-molecular-mass isoform, comprise all thymocytes with clonogenic potential and include all major subsets defined by CD4 and CD8. We have proposed that a CD45 p180⁻ lineage exists in the human thymus and that this lineage results in the production of mature thymocytes and thymic emigrants. The objective of the present study was to determine by DNA analysis whether the degree of cell cycling in subsets of human thymus, defined by selective expression of high-molecular-mass isoforms of CD45, was sufficient to account for the generation of thymic emigrants. Multicolor immunofluorescence analysis of surface markers and 7-amino actinomycin D as well as propidium iodide staing was used to measure the DNA content of thymic subsets. Negative depletion methods were used to isolate and characterize human thymocyte subsets defined by CD45 isoform, CD3, CD4, and CD8, and subsequently to determine the cell cycle status of the isolated subsets by flow-cytometric analysis of cellular DNA content. CD3^−/lo thymocytes had a high number and CD1^−/lo thymocytes a low number of cycling cells, consistent with murine data. CD45 p 180⁻ cells, as well as the CD4⁻8⁻ and CD3⁻4⁻8⁻ subsets which express high molecular-weight CD45 isoforms, exhibited a significant number of cycling cells. Since CD45 p180- thymocytes exhibited a significant number of cycling cells, based on numerical arguments we conclude that this cycling thymocyte fraction is capable of generating the daily requirements of mature thymocytes and thymic emigrants.     

The Secreted Larval Acidic Proteins (SLAPs) of Onchocerca spp. are encoded by orthologues of the alt gene family of Brugia malayi and have host protective potential

Onchocerca volvulus is a tissue-dwelling, vector-borne nematode parasite of humans and the causative agent of onchocerciasis, or 'River Blindness'. Resistance to infection is associated with immune responses to the infective, third-stage (L3) larvae. The antigens of greatest interest for their vaccine potential are surface and secreted molecules. We have previously identified a family of Secreted Larval Acidic Proteins (SLAPs) from the L3 larvae of O. volvulus by biosynthetic labelling. Here, we provide further characterisation of these molecules following cloning and expression of the corresponding cDNAs. Using protein sequencing, we show that SLAPs are members of the alt gene family, first described in the lymphatic filarial parasite, Brugia malayi. Ov-ALT-1 and Ov-ALT-2 correspond with 20 and 18kDa SLAPs. Both proteins are highly acidic and related by sequence, differing chiefly in an 8-amino acid deletion from Ov-ALT-2. By immunochemistry, we confirm that Ov-ALTs are highly stage-specific, being expressed exclusively in late L2 and L3 larvae during growth in the vector. They are synthesised and stored in the glandular oesophagus. Secretion is triggered by the resumption of development in the definitive host and occurs via the pseudocoelom and cuticle. Serological responses in humans to recombinant Ov-ALT-1 indicate that the level of IgG production may be governed by the force of transmission but does not overtly reflect infection status. Immunisation of mice with recombinant Ov-ALT-1 resulted in a modest level of protection against challenge with O. volvulus L3 larvae (P = 0.036). We conclude that Ov-ALT genes, like those of other filariae, are of interest from the standpoint of parasite transmission and infectivity. They may also offer promise as components of a future sub-unit vaccine should the means to enhance protection be achieved.     

Multiple signal transduction pathways activated through the T cell receptor for antigen.

The T cell receptor for antigen (TCR) is a multichain complex on the surface of T lymphocytes which binds peptide antigen and transduces a transmembrane signal leading to IL-2 secretion. Engagement of the TCR leads to activation of a tyrosine phosphorylation pathway and a phospholipase C (PLC) pathway leading to activation of protein kinase C (PCK). Currently available data suggest that the primary event in signal transduction is tyrosine kinase activation, since when this pathway is inhibited, PLC activation is blocked and there is no production of IL-2. The nature of the tyrosine kinase which initiates the signaling cascade is currently unknown. The CD4/CD8 associated kinase p56lck clearly plays a role in tyrosine phosphorylation, but it is clearly not the only tyrosine kinase involved. Studies demonstrating physical association of p59lyn with the TCR implicate fyn as an important candidate for the TCR tyrosine kinase. The protein tyrosine phosphatase CD45 also plays a critical early role in signal transduction since in cells where it is deficient, neither tyrosine kinase activation nor later signaling events are seen. The importance of the PLC/PKC pathway is illustrated by the fact that activation of this pathway alone may lead to IL-2 production. However, there may also be other mechanisms which can generate an IL-2 response. Two proteins known to be involved in growth regulation--p21ras and c-raf--have now been shown to be downstream targets of the PLC/PKC pathway.     

Don't just do something,stand there! The value and art of deliberate clinical inertia

It can be difficult to avoid unnecessary investigations and treatments, which are a form of low‐value care. Yet every intervention in medicine has potential harms, which may outweigh the potential benefits. Deliberate clinical inertia is the art of doing nothing as a positive response. This paper provides suggestions on how to incorporate deliberate clinical inertia into our daily clinical practice, and gives an overview of current initiatives such as ‘Choosing Wisely’ and the ‘Right Care Alliance’. The decision to ‘do nothing’ can be complex due to competing factors, and barriers to implementation are highlighted. Several strategies to promote deliberate clinical inertia are outlined, with an emphasis on shared decision‐making. Preventing medical harm must become one of the pillars of modern health care and the art of not intervening, that is, deliberate clinical inertia, can be a novel patient‐centred quality indicator to promote harm reduction.     

How do people with knee pain from osteoarthritis respond to a brief video delivering empowering education about the condition and its management?

ObjectiveTo evaluate responses by people with knee osteoarthritis to a brief educational video about their condition that aimed to empower and motivate effective self-management. The video content addressed psychosocial contributors to pain and barriers to behaviour change.MethodsA mixed methods design, including a survey and semi-structured interviews, was used to collect data from 118 people (46–83 years, 78% female) with knee osteoarthritis.ResultsQuantitative data analysis showed the video was rated positively on 0–6 scales for enjoyability (mean 5.0), helpfulness (4.9), relevance (5.0) and believability (5.4). The majority would recommend the video (89%), learned new information (78%) and/or reported intentions to change behaviour (78%). A minority disliked aspects of the video (23%). The thematic analyses identified three main themes: Reactions to the video, including emotions; Learning from the video, including new knowledge and empowerment, but also unmet information needs or disagreement; and Intentions, including behaviour changes, cognitive changes and help seeking.ConclusionEducation about knee osteoarthritis with a focus on empowerment is well received by people with the condition, although some discordant views emerged.Practice implicationsThe educational video about knee osteoarthritis can be recommended to promote effective self-management and counteract potential drawbacks associated with biomedical-based education.     

Kinetics of mature T-cell development in the thymus.

We have reexamined the balance between cell birth, cell maturation, and cell death in the thymus by labeling dividing thymocytes and their progeny in vivo with [3H]-thymidine, isolating clearly defined subpopulations by fluorescence-activated cell sorting, and determining the distribution of label by autoradiography. When mature thymocytes were precisely defined (as CD4+CD8- CD3+ or CD4-CD8+ CD3+) and separated from immature single positives (CD4+CD8- CD3- and CD4-CD8+ CD3-), a lag was observed in the rate of entry of [3H]thymidine into mature cells. Thus, many of the mature thymocytes appear to derive from a small nondividing cortical thymocyte pool, rather than originating directly from the earliest dividing CD4+CD8+ blasts. There was little evidence for cell division during or after mature thymocyte formation, suggesting a one-for-one differentiation from cortical cells rather than selective clonal expansion. The rate of production of mature single positive thymocytes agreed closely with estimates of the rate of export of mature T cells from the thymus and was only 3% of the rate of production of double-positive cortical thymocytes. This was compatible with a stringent selection process and extensive intrathymic cell death and suggested that no extensive negative selection occurred after the mature cells were formed.