Coupling of vinculin to F-actin demands Syndecan-4 proteoglycan.

Syndecans are heparan sulfate proteoglycans characterized as transmembrane receptors that act cooperatively with the cell surface and extracellular matrix proteins. Syn4 knockdown was performed in order to address its role in endothelial cells (EC) behavior. Normal EC and shRNA-Syn4-EC cells were studied comparatively using complementary confocal, super-resolution and non-linear microscopic techniques. Confocal and super-resolution microscopy revealed that Syn4 knockdown alters the level and arrangement of essential proteins for focal adhesion, evidenced by the decoupling of vinculin from F-actin filaments. Furthermore, Syn4 knockdown alters the actin network leading to filopodial protrusions connected by VE-cadherin-rich junction. shRNA-Syn4-EC showed reduced adhesion and increased migration. Also, Syn4 silencing alters cell cycle as well as cell proliferation. Moreover, the ability of EC to form tube-like structures in matrigel is reduced when Syn4 is silenced. Together, the results suggest a mechanism in which Syndecan-4 acts as a central mediator that bridges fibronectin, integrin and intracellular components (actin and vinculin) and once silenced, the cytoskeleton protein network is disrupted. Ultimately, the results highlight Syn4 relevance for balanced cell behavior.

Three-dimensional stress analysis for the mechanics of plantar ulcers in diabetic neuropathy.

In diabetic neuropathic subjects, the hardness of foot sole soft tissue increases, and its thickness reduces, in different foot sole areas. Finite element analysis (FEA) of a three-dimensional two-arch model of the foot was performed to evaluate the effect of foot sole stresses on plantar ulcer development. Three sets of foot sole soft-tissue properties, i.e. isotropic (with control hardness value), diabetic isotropic (with higher hardness value) and anisotropic diabetic conditions, were simulated in the push-off phase, with decreasing foot sole soft-tissue thicknesses in the forefoot region, and the corresponding stresses were calculated. The results of the stress analyses for diabetic subject (anisotropic) foot models showed that, with non-uniformly increased hardness and decreased foot sole soft-tissue thickness, the normal and shear stresses at the foot sole increased (compared with control values) by 52.6% and 53.4%, respectively. Stress analyses also showed high ratios of gradients of normal and shear stresses of the order of 6.6 and 3.3 times the control values on the surface of the foot sole, and high relative values of stress gradients for normal and shear stresses of 6.25 and 4.35 times control values, respectively, between the foot sole surface and the adjacent inner layer of the foot sole, around a particular region of the foot sole with anisotropic properties. These ratios of high gradients and relative gradients of stresses due to changes in soft-tissue properties may be responsible for the development of plantar ulcers in diabetic neuropathic feet.

The psychosocial experience of people with sickle cell disease and its impact on quality of life: Qualitative findings from focus groups.

OBJECTIVES: In this exploratory study, an in-depth analysis of accounts of the experiences of people with sickle cell disease (SCD) was undertaken to gain an understanding of the psychosocial impact of the disease. An additional aim of the study was to determine whether these experiences could be conceptualized in terms of quality of life as defined by the World Health Organization (WHOQOL) with the intention of informing psychosocial research. DESIGN: This study utilized a series of non-directive, patient-led, focus groups that specifically addressed the ways in which sickle cell disease impacts on life. Participants were recruited from four centres in London and eight focus group discussions (each one hour in length) were held separately for each centre. METHOD: Altogether 32 hours of focus group materials were tape-recorded and transcribed verbatim. Data were analysed using a phenomenological approach to identify emerging themes. RESULTS: Six themes were identified: Growing up with SCD; Education; Impact of the unremitting nature of the disease; Employment; Effects on relationships; and Hospitalization. CONCLUSION: This research has clearly shown that SCD carries a huge psychosocial burden impacting on physical, psychological, social and occupational well-being as well as levels of independence and environment. These aspects of life are equivalent to the core domains of the multi-dimensional WHOQOL and consequently we have argued that SCD undermines quality of life in important ways. The paper provides a rich source of qualitative data to complement quantitative findings and provides detail of the complex human processes and experiences consequent on a life-long chronic illness such as SCD.

Psychological distress and coping in sickle cell disease: comparison of British and Jamaican attitudes.

OBJECTIVE: To investigate possible differences in coping mechanisms in the painful crisis between Jamaican and London patients with homozygous sickle cell disease. DESIGN: Patients recruited from two London hospitals and the MRC Laboratories (Jamaica) at the University of the West Indies, Kingston, Jamaica were assessed using a questionnaire design. Patients with homozygous sickle cell disease were included, 30 in London and 30 in Jamaica. RESULTS: Jamaican patients in Jamaica had less general anxiety, a lower emotional response to pain, lower levels of perceived pain, and felt better able to decrease their pain. London patients believed that the disease had a more marked effect on their quality of life. CONCLUSION: Understanding the differences between patients' response to pain and their coping ability between Jamaican and UK patients may have important lessons for evolving effective management in the UK.

Cognitive-behavioural therapy for the management of sickle cell disease pain: identification and assessment of costs.

OBJECTIVE: The aim of the present study was to investigate the economic validity of using a psychological intervention in the management of sickle cell disease (SCD). Thomas et al. (Br J Health Psychol 1999; 4: 209-29) concluded that cognitive-behaviour therapy (CBT) appears to be immediately effective for the management of SCD pain in terms of reducing psychological distress pain as well as improving coping. METHOD: The costs of management of SCD were evaluated using a societal viewpoint. This approach includes health and social services as well as costs privately borne by informal carers, but it did not include the economic loss due to patients' foregone earnings. Cost profiles were constructed for each patient taking account of cost generating events 12 months before and 12 months after CBT. RESULTS: The hypothesis of the present study, stating that CBT is economically efficient, was confirmed. However, analysis of longitudinal data suggests that CBT is most cost-effective during the first 6 months after the intervention. CONCLUSION: The present findings suggest the need for CBT to be integrated into the normal package of care available for all patients with SCD. The clinical implication is that CBT should be routinely offered to patients on a 6-monthly basis.

Identification of UreR binding sites in the Enterobacteriaceae plasmid-encoded and Proteus mirabilis urease gene operons.

The closely related Proteus mirabilis and Enterobacterlaceae plasmid-encoded urease genes are positively regulated by the AraC-like transcriptional activator UreR. In the presence of the effector molecule urea, UreR promotes transcription of ureD, the initial gene in the urease operon, and increases transcription of the divergently transcribed ureR. Here, we identify UreR-specific binding sites in the ureRp-ureDp intergenic regions. Recombinant UreR (rUreR) was expressed and purified, and gel shift and DNase I protection assays were performed with this protein. These analyses indicated that there are two distinct rUreR binding sites in both the plasmid-encoded and P. mirabilis ureRp-ureDp intergenic regions. A consensus binding site of TA/GT/CA/TT/GC/TTA/TT/AATTG was predicted from the DNase I protection assays. Although rUreR bound to the specific DNA binding site in both the presence and the absence of urea, the dissociation rate constant k-1 of the rUreR-DNA complex interaction was measurably different when urea was present. In the absence of urea, the dissociation of the protein-DNA complexes, for both ureRp and ureDp, was complete at the earliest time point, and it was not possible to determine a rate. In the presence of urea, dissociation was measurable with a k-1 for the rUreR-ureRp interaction of 1.2 +/- 0.2 x 10(-2) s-1 and a k-1 for the rUreR-ureDp interaction of 2.6 +/- 0.1 x 10(-3) s-1. This corresponds to a half-life of the ureRp-rUreR interaction of 58 s, and a half-life of the ureDp-rUreR interaction of 4 min 26 s. A model describing a potential role for urea in the activation of these promoters is proposed.

Anticipating and experiencing post-operative pain: the patients' perspective.

This study uses a qualitative approach to explore patients' expectations and experiences of pain, factors contributing to the effective/ineffective management of their pain and strategies patients reported as helpful when experiencing pain. Ten patients on a mixed surgical ward at a District General Hospital in the south of England participated in the study. Pain scores, using a visual analogue scale, were obtained for 'expected' pain preoperatively and 'worst pain experienced'. A taped in-depth interview exploring patients' experience of pain after surgery took place on the fifth post-operative day. Details of analgesia were also collected for the 5 days following surgery. Patients expected pain after surgery but the intensity of the pain they experienced was often significantly greater than anticipated. Lack of information, inadequate pain assessment and ineffective pain control contributed to this finding. It is suggested that new pain technology, such as epidural and patient-controlled analgesia, may not change the prevalence and incidence of pain unless the systems these technologies are placed within also change.

Patient-controlled analgesia (PCA): does time saved by PCA improve patient satisfaction with nursing care?

This quasi-experimental study compared the degree of satisfaction with nursing care among patients receiving post-operative pain relief via patient-controlled analgesia (PCA) and those receiving traditional intramuscular injection (IMI) regimes. This study, which involved a total of 79 adult patients (mainly female) undergoing major abdominal surgery, was comprised of two main parts. First, the amount of time taken by nurses to carry out pain control procedures on 11 matched pairs of PCA and traditional patients was recorded. Second, all patients were asked to fill in a questionnaire regarding their satisfaction with the quality of nursing care they had received on their third post-operative day. The findings indicated that PCA did save time and this time saving could improve the nursing care quality of the whole ward, though not necessarily resulting in higher satisfaction amongst those patients who used PCA. Interestingly, younger and the more highly educated patients were found to be especially critical and be less satisfied with care. The implications for nursing practice and management are addressed, with special emphasis placed on the notion that time saved with PCA should be used to increase patient-nurse contact and should not be used to compensate for a reduction in nursing staff.

The management of sickle cell crisis pain as experienced by patients and their carers.

This study sought to provide insights into the personal experiences of individuals with sickle cell disorder and nurses involved in the management of painful sickle cell crisis. The sample consisted of 10 patients who experienced hospitalization for the management of pain during sickle cell crisis and 10 nurses who have cared for patients during such crises. The method of data collection used a combination of group and individual interviews, utilizing a 'guided conversation approach'. Data analysis consisted of content analysis of transcribed interviews which resulted in the identification of the following categories of problems: poor pain management, anxieties about pethidine, loss of control, lack of individuality and playing up. The results revealed that pain control during sickle cell crisis is often inadequate, with nurses admitting that they often have to resort to 'trial and error' strategy to manage pain. The findings are discussed in terms of attitudinal and knowledge factors and an individualized approach to pain management.

Patient-controlled analgesia: a new method for old.

Patient-controlled analgesia (PCA) has successfully made the transition from a research tool for the investigation of pain, to a wider clinical utility as method of pain control. Reliable and sophisticated PCA systems have been commercially available for some time. The technique has been most commonly used for control of postoperative pain, but has also been successfully used during labour, after burns, in acute painful medical conditions and in terminal care. It is generally more effective than the traditional methods of postoperative pain control but not automatically so. The choice of opioid, the settings chosen for demand dose and the lockout interval will greatly influence the effectiveness of this method of analgesia. Psychological variables are also important in predicting the efficacy of PCA.

Ethnic differences in the experience of pain.

Investigations of ethnic differences in pain experience have been largely confined to the hospital or laboratory. Such studies are limited by the potentially confounding effects of the expectation of pain in the former and of little or no pain in the latter. The present investigation overcomes some of these methodological problems by studying ethnic differences in pain experience following ear-piercing. Afro-West Indian, Anglo-Saxon and Asian subjects (n = 84) completed a pain questionnaire and two rating scales after ear-piercing. Half the subjects were told the study was about pain and half that it was concerned with sensation. There were highly significant ethnic differences in pain ratings. The pain condition produced higher ratings than the sensation condition but there were no significant sex differences. The results are discussed in the context of subjects' ratings of their parents' attitudes to minor injury and their own ability to cope with pain. It is argued that investigation of the bases of ethnic differences in pain experience is important in order to develop maximally efficient pain control regimes for all sections of the populations.

Ethnic differences in the experience of pain

Investigations of ethnic differences in pain experience have been largely confined to the hospital or laboratory. Such studies are limited by the potentially confounding effects of the expectation of pain in the former and of little or no pain in the latter. The present investigation overcomes some of these methodological problems by studying ethnic differences in pain experience following ear piercing. Afro-West Indian, Anglo-Saxon and Asian subjects (n=84) completed a pain questionnaire and two rating scales after ear-piercing. Half the subjects were told the study was about pain and half that it was concerned with sensation. There were highly significant ethnic differences in pain ratings. The pain condition produced higher ratings than the sensation condition but there were no significant sex differences. The results are discussed in the context of subjects' ratings of their parents' attitudes to minor injury and their own ability to cope with pain. It is argued that investigation of the bases of ethnic differences in pain experience is important in order to develop maximally efficient pain control regimes for all sections of the population. (AU)

Particle breakdown and rumen digestion of fresh ryegrass (Lolium perenne L.) and lucerne (Medicago sativa L.) fed to cows during a restricted feeding period.

1. Five rumen-fistulated cows were given freshly cut ryegrass (Lolium perenne L.) and lucerne (Medicago sativa L.), on separate occasions, to compare rates of particle breakdown and aspects of rumen fermentation. 2. Cattle were required to consume their daily allowance (offered ad lib.) in two 2 h feeding periods daily. 3. During the first 2 h feeding period, dry matter (DM) intakes of ryegrass (4.75 kg) and lucerne (4.85 kg) were similar. Eating reduced 46% of ryegrass and 61% of lucerne to a size able to pass a 2 mm sieve (P less than 0.001). Rumen DM particles retained on the 2 and 4 mm sieves had a low probability of passage out of the rumen, and accounted for only 6% of faecal DM with both feeds. 4. Ryegrass was cleared from the rumen more slowly than lucerne. During eating, rumen DM particles which could not pass the 2 mm sieve increased from 323 to 511 g/kg for ryegrass and from 201 to 389 g/kg for lucerne. The rate of particle size reduction for lucerne stem was similar to that for ryegrass. 5. When lucerne was eaten the increases in rumen volatile fatty acid (VFA) and ammonia concentrations were much greater than for ryegrass (P less than 0.001). The proportions of plant chlorophyll released during eating were similar for both feeds (0.570 and 0.607), but 2 h after eating 22.3 g had been released from lucerne (79.1%) compared with 15.0 g from ryegrass (63.8%). The flux of water from the rumen to the omasum was similar for ryegrass (10.2 litres/h) and lucerne (12.7 litres/h) during eating, but declined to 6.0 litres/h after eating with the lucerne diet.

The treatment of ruptures of multiple extensor tendons at wrist level by a free tendon graft in the rheumatoid patient.

We report the results of the treatment of multiple ruptures of extensor tendons to the fingers at wrist level in the rheumatoid patient by free tendon grafts. Twenty-three patients averaged 65 degrees of active motion at the metacarpophalangeal joints when seen at an average follow-up of 43 months.

Plasma histamine levels following atracurium.

Plasma histamine levels were determined in 41 patients, 1.5 and 4 minutes after the intravenous administration of 0.6 mg/kg of atracurium. Clinical features of histamine release were sought at the time of blood sampling. Sixteen patients had elevation of plasma histamine 2.6 (SD 1.2) ng/ml 1.5 minutes after the injection of atracurium. Plasma histamine had returned to control levels at 4 minutes. There was a poor correlation between plasma histamine levels and the clinical manifestations observed. We conclude that atracurium has a low plasma histamine release potential and that cutaneous reactions after atracurium do not always indicate that plasma histamine levels are elevated.