Introduction of the Liverpool Care Pathway for end of life care to emergency medicine.

AIM: To improve the care of patients presenting to the emergency department who are acutely dying or those in whom further disease-modifying treatment is not appropriate. DESIGN: A quality improvement report on the implementation of a modified Liverpool Care Pathway for the Dying Patient (LCP) in an emergency medicine department. SETTING: The emergency medicine department of Ninewells Hospital, Dundee. Ninewells Hospital is the tertiary referral and teaching hospital for the east coast of Scotland and North East Fife. KEY MEASURES FOR IMPROVEMENT: The pathway was introduced after a 2001 study and a 2003 audit showed that the department had an increasing role in the care of the acutely dying, but some inconsistency in approach. Key measures for improvement were to improve communication between staff, improve the consistency of care and improve the perceived quality of care given. Senior decision making remains a crucial element of the pathway. STRATEGIES FOR CHANGE: A modified LCP was developed and launched in November 2005. Change was managed via a series of meetings and a pilot process. Serial review and audit allowed ongoing quality review of the pathway and improvements. RESULTS: The care of the dying patient has become a more consistent and positive endeavour. Nursing staff are very satisfied with its use, and it is hoped that the LCP pathway can be developed further within the organisation. CONCLUSIONS: It has been a rewarding undertaking to improve the care of dying patients, but one which has taken time and has required consistent management of change to promote the positive outcomes.

Retinoid-specific induction of differentiation and reduction of the DNA synthesis rate and tumor-forming ability of a stem cell line from a rat mammary tumor.

Differentiation of the stem cell line rat mammary (Rama) 25 to alveolar-like cells can be monitored by the increase in production of domes (hemispheric blisters) in the cell monolayer and immunoreactive casein in the tissue culture medium. This step was accelerated not only by the synthetic inducer dimethyl sulfoxide (DMSO) but also by all-trans-retinol, all-trans-retinal, all-trans-retinoic acid (RA), and all-trans-retinyl acetate (concentration range, 0.04-4 microM) in the presence of the hormones prolactin, hydrocortisone (HC), insulin, and 17 beta-estradiol; 9-cis-all-trans-retinal was without effect. A combination of RA and HC was active in producing doming, whereas RA, all four hormones, and serum were required for maximum production of immunoreactive casein. The retinoids in the same concentration range also caused a reduction in the DNA synthetic rate in a similar time period. When Rama 25 cells were treated with RA and the four hormones yielding the droplet and doming cultures, subsequent injection of these cells into young, female inbred nu/nu (nude) mice led to a reduced incidence of tumors compared with injections of untreated cells. Tumorigenic variant cell lines were selected previously from Rama 25 that were either elongated and failed to differentiate at all to doming and casein-secreting cultures (Rama 521) or that did so spontaneously but whose rates were not accelerated by addition of DMSO (Rama 259). Both Rama 521 and Rama 259 failed to respond to the retinoids and hormones in producing domes and immunoreactive casein, in decreasing DNA synthetic rates, and in lowering the incidence of tumors induced by injection of the cell lines into nude mice. Thus the anticancer activity of the retinoids in rat mammary gland carcinogenesis may be due in part to their differentiation-inducing properties.

Measurement of bone collagen degradation in hyperthyroidism and during thyroxine replacement therapy using pyridinium cross-links as specific urinary markers.

UNLABELLED: Urinary excretion of the bone collagen derived pyridinium cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) was measured in 19 patients (4 M:15 F) with untreated thyrotoxicosis, and 20 pre-, and 20 postmenopausal women taking T4 100-200 micrograms daily for autoimmune hypothyroidism. Both PYD and DPD excretion (nanomoles per mmol creatinine) was elevated in the thyrotoxic patients compared to 287 controls; median 131 vs. 26 and 37.5 vs. 7.2, respectively, P less than 0.0001. In premenopausal women mean urinary pyridinium cross-link excretion and serum osteocalcin levels were similar in both T4-treated and matched control groups, despite suppression of serum TSH concentrations to below 0.1 mU/L in 14 of the 20 taking T4. In postmenopausal women mean (+/- 1 SE) urinary PYD excretion (nanomoles per mmol creatinine) was raised in those taking T4, relative to euthyroid controls; 40.0 +/- 2.7 vs. 32.1 +/- 2.3, P less than 0.05. DPD excretion and serum osteocalcin levels were also higher, but not significantly. When only the T4-treated women with a subnormal serum TSH were considered the difference in PYD excretion was more marked, and mean DPD excretion was also significantly elevated; 13.7 +/- 1.3 vs. 10.1 +/- 0.8, P less than 0.05. CONCLUSION: bone collagen breakdown is increased in thyrotoxicosis, and in postmenopausal women taking sufficient T4 to suppress serum TSH. Similarly treated premenopausal women appear to be at lower risk.

Anterior cruciate ligament reconstruction using part of the patellar tendon as a free graft.

We have reviewed 40 patients after replacement of a ruptured anterior cruciate ligament with a free graft of the medial third of the patellar tendon, combining this in 17 of the cases with a MacIntosh extra-articular tenodesis. The average age of the patients at operation was 25.4 years; instability of the knee had been present for 1.5 to 9 years, and the mean follow-up was 2.9 years. The results, assessed on subjective stability, were good in 29 patients, over half being able to return to their original sport, and fair in eight. The technique of operation for free patellar tendon grafting is described in detail and the indications for this and for an additional MacIntosh tenodesis are discussed.

Meniscectomy for tears of the meniscus combined with rupture of the anterior cruciate ligament.

A group of 40 patients with unstable knees due to a combination of a meniscal tear with a rupture of the anterior cruciate ligament was studied to assess the effects of treatment by meniscectomy alone. The results were assessed both subjectively and objectively, but emphasis was placed on the symptoms rather than the physical signs of instability. Meniscectomy alone cured the symptoms of instability in 22 of the patients and a further eight required no further surgical treatment; bucket-handle tears were associated with a good result and posterior-horn tears with a poor result. The remaining 10 patients later underwent an additional procedure to reconstruct the ligament because of persisting symptoms. It was concluded that in patients with this combined lesion the torn meniscus should be dealt with first. In young patients with a posterior-horn tear it would be justifiable to perform a ligamentous reconstruction at the same time as the meniscectomy.

Neuropathic osteonecrosis of the lateral femoral condyle in childhood. A report on four cases.

Four children are described, each with spontaneous osteonecrosis affecting nearly one-third of the lateral femoral condyle. All the children had a motor and a sensory deficit in the affected limb: two had been previously treated for neuroblastoma of the spine, one for an infected lumbar dermoid cyst and one had spina bifida. We consider that these disorders, singly or in combination, may lead to repeated excessive loading of the lateral femoral condyle, which cannot be appreciated in a knee that is not protected by normal sensation.

Initial stages in the development of valid criteria for the replacement of amalgam restorations.

OBJECTIVES: Replacement amalgam restorations account for the largest single cost in the General Dental Services in Scotland. There is little practical advice available to practitioners on the maintenance and replacement of amalgam restorations. A distance learning package is being prepared for distribution to general dental practitioners in Scotland and this paper describes the initial stages in the development of the policy statements for the proposed package. METHODS: In the first stage proposals are being developed by a panel of dental academics using a modified Delphi technique. This technique is designed to produce a consensus view. Seventeen statements have been set out by the expert group. RESULTS AND CONCLUSIONS: While agreement was rapidly reached that 'ditching' of amalgam restoration margins did not justify their replacement and that repair was preferable to total replacement, some difficulty was experienced in arriving at a consensus view on the correct management of 'white spot' lesions at restoration margins and dentinal staining adjacent to amalgam restorations. The next stage in the development will be to present these statements to a selected panel of general dental practitioners and to develop their consensus view of the proposals, again using the Delphi technique.

General practitioners' perceptions of the effects of a distance learning programme.

A postal/telephone survey of 400 general dental practitioners working in the Greater Glasgow and Lanarkshire Health Board areas was carried out between May and September 1990. The aims were to monitor any changes in the use of sealant restoration techniques in the last year, to investigate the practitioners' perception of the effects of a distance learning programme on their techniques and to provide data on the use of the techniques in the final months of the 'old contract'. A response rate of 66.7% was achieved. Eighty-eight per cent of the group were placing sealant restorations. Dentists' perceptions of the impact of the distance learning programme were encouraging. In key areas of practice, 16-44% of the group reported changes in their clinical techniques as a result of reading the programme.

Reported use of sealant restorations in a group of general practitioners in the west of Scotland.

A postal/telephone survey of 452 general practitioners working in the Greater Glasgow and Lanarkshire Health Board areas was carried out between March and June, 1989. The aim was to investigate the use of sealant restorations under section 6 of the National Health Service fee scale for general dental practitioners. Section 6 itemizes fees for fissure sealant, glass-ionomer cement plus sealant, composite resin plus sealant and the laminate restoration. A response rate of 83% was obtained. Eighty-one per cent of the respondents were placing sealant restorations, but less than half were using the laminate or sandwich technique. A wide variety of materials and curing lights were employed. Enamel etching times varied considerably and rubber dam was seldom used. Eighty-nine per cent indicated that they would welcome illustrated fact sheets demonstrating the use of sealant restorations.

Short-stay, specialist beds in a UK teaching hospital as a model to integrate palliative care into the acute hospital culture.

Hospital patients should have access to effective palliative care. In our study, three short-stay beds were re-allocated to specialist palliative care as part of a pilot programme. This paper describes the first 100 admissions of patients with inadequately controlled symptoms or distress. Median pain and distress scores were both seven out of a maximum of 10 (interquartile ranges [IQR] 4-10 and 1-10 respectively), reducing to 3.5 (IQR 1-5) and 0 (0-5) after 48 hours. Median length of stay was five days (IQR 3-10); 77% of patients were discharged: 32% to home, 26% to a hospice or community hospital, 19% to their original ward for treatment and 23% died in the unit. A unit education programme introduced as part of the study attracted 600 staff members. Pain and distress were rapidly improved by brief, intense palliative care in a small onsite facility. The pilot programme also influenced the understanding of palliative care in the hospital, demonstrating what it offered patients, family and staff. It demonstrated effective, concurrent working alongside an active disease-management approach, and encouraged collaborative discussions about the goals of care.

Is pelvic floor morphology a predictor of successful pessary retention? Original research and review of the literature

Background. Vaginal pessaries are known to be an effective treatment modality for pelvic organ prolapse (POP). Pessaries form an important part of the physician's armamentarium in the treatment of POP, but currently many of the factors affecting their successful use are poorly understood. Objectives. To determine the association between pessary retention (PR) at 1 year, and functional pelvic floor morphology, i.e. levator hiatal distance and area, and levator avulsion. Methods. This retrospective study reviewed the records of 73 patients with symptomatic POP at a tertiary urogynaecological centre. This multi-ethnic cohort had previously been studied for pelvic-floor morphology, had had 4D transperineal pelvic-floor ultrasound, and had opted for a vaginal pessary as a treatment option. Results. Our population had a mean age of 59.4 (range 32 - 91) years, and mean body mass index of 29.4 (range 20 - 42) kg/m2, with a mean assessment of stage 3 in the Pelvic Organ Prolapse Quantifications System (POP-Q). The level of prolapse was found to be related to PR (p=0.077). We further explored this concept using symmetric measures of association (γ=­0.353), indicating that PR decreases with increasing prolapse severity. PR was also found to be inversely associated with prior pelvic reconstructive surgery (n=63; p=0.055; γ=­0.417). There was a strong correlation that failed, however, to achieve significance by a small margin (p=0.052) between hiatal distance on contraction and PR. Conclusion. This study found an inverse relationship between PR and hiatal distance on contraction, prior pelvic surgery and the severity of prolapse. This was a pilot study with a limited number of participants, and the authors plan a prospective study to further clarify the association between long-term PR and functional pelvic floor morphology

Identification of novel, stage-specific polypeptides associated with the differentiation of mammary epithelial stem cells to alveolar-like cells in culture.

A linear pathway of morphologically intermediate cells has been identified between the cuboidal epithelial stem cells and the doming alveolar-like cultures of the cell line Rat Mammary (Rama) 25 in the order: cuboidal----grey----dark----dark droplet cell----doming cultures. The overall process can be accelerated by dimethyl sulfoxide (DMSO) or retinoic acid (RA) in the presence of mammotrophic hormones. From 400-450 [35S]methionine-labeled polypeptides that are routinely separated by two-dimensional gel electrophoresis approximately only 3% change during this process. As the Rama 25 cultures become confluent, three polypeptides of molecular weights (MW) 35 kD (pl = 7.7), 45 kD (pl = 7.5) and 33 kD (pl = 7.7) increase dramatically in radioactive abundance. These increases correspond to increases in numbers of grey cells for the 35 kD polypeptide, to increases in numbers of dark cells together with increases in peanut lectin-binding-ability for the 45 kD polypeptide, and to increases in the numbers of dark cells and in the numbers of droplet cells for the 33 kD polypeptide. After treatment with DMSO, RA or in spontaneously doming cultures, a second set of four polypeptides of MW 26 kD (pl = 5.9), 27 kD (pl = 6.2), 30 kD (pl = 7.2), and the same 33 kD polypeptide as above increase with the increase in numbers of droplet cells, domes, and increase in casein secretion. A variant of Rama 25, Rama 259, which fails to produce droplet cells, domes, or to secrete casein with DMSO and hormones also shows the same changes in the first set but not in the second set of polypeptides. The elongated, myoepithelial-like cell line derived from Rama 25, Rama 29, which cannot undergo any of the above intercellular conversions, fails to show changes in any of these polypeptides. Major changes in radioactive polypeptides have been confirmed for nonradioactive polypeptides and for polypeptides labeled for 4 hr with [35S]methionine. The synthesis of these novel polypeptides thus marks specific morphological stages of the differentiation of mammary epithelial stem to alveolar-like cells in culture, and as such may mark similar differentiation stages in vivo.

Microtubule-disrupting drugs increase the frequency of conversion of a rat mammary epithelial stem cell line to elongated, myoepithelial-like cells in culture.

Rat mammary (Rama) 25 cuboidal epithelial stem cells convert at a low frequency to elongated, Thy-1-positive, myoepithelial-like cells in culture; one such cell line is termed Rama 29. Addition of increasing concentrations of the microtubule-disrupting drug colchicine to sparse cultures of Rama 25 dramatically increases the percentage of colonies containing elongated cells and the percentage of Thy-1-positive cells when the drug is removed. Similar results on the formation of elongated cell colonies are obtained with other microtubule disruptors, such as vinblastine, vincristine, demecolcine, and nocodazole. The inactive analogues of colchicine beta- and delta-lumicolchicine and the microfilamental-disruptors cytochalasin B and D are without effect on the formation of elongated cell colonies and Thy-1-positive cells. For a given concentration of colchicine the percentage of elongated cell colonies and Thy-1-positive cells increases the longer the cells are exposed to the drug (range 8-96 hr) and the longer the drug-treated cultures are subsequently grown in drug-free medium. Colchicine fails to display this morphological change on Rama 29 elongated cells and on Rama 600 epithelial cells from a rat mammary metastasizing tumor. Immunofluorescent localization of antisera to tubulin confirms that colchicine disrupts the microtubules in all three cell lines at similar concentrations (0.1 to 1 microM) to those required to increase the percentage of elongated cell colonies in Rama 25. The DNA synthesis inhibitor cytosine arabinoside fails to inhibit this conversion process, and time-lapse cinematographic studies confirm that the conversion of a cuboidal to an elongated cell can take place without cell division. However, cell division may sometimes be required for subsequent stabilization events. Treatment of Rama 25 cells with colchicine under the same conditions also increases the abundance of elongated cell (Rama 29)-associated polypeptides, and elongated cell clones isolated after such treatment show an overall pattern of protein synthesis very similar to that of Rama 29.

Instability of the ankle due to a separate centre of ossification in the lateral malleolus.

A case of recurrent instability of the ankle is reported. It was associated with a separate centre of ossification in the lateral malleolus. While such extra ossification centres for both malleoli are recognized, they have not hitherto been incriminated as a cause of instability. The successful treatment of this case is described and the incidence and significance of separate ossification centres for the malleoli are discussed.

Differentiation of mammary epithelial stem cells to alveolar-like cells in culture: cellular pathways and kinetics of the conversion process.

The cuboidal epithelial stem cell line Rat Mammary (Rama) 25 can differentiate in culture to droplet, alveolar-like cells that form domes, secrete small amounts of casein, and bind peanut lectin after treatment with neuraminidase. Differentiation to droplet cells is accelerated by dimethyl sulfoxide (DMSO). Morphologically intermediate states (gray and dark) which occur in the order: cuboidal----gray----dark----dark droplet----doming cells have been identified along this pathway by time-lapse cinematography. The dark and dark droplet states are associated with increased peanut lectin binding capacity whereas casein is secreted mainly by cells in domes. Cells in cultures containing low concentrations of DMSO (less than 56 mM) acquire droplets predominantly in the dark state, whereas with higher concentrations of DMSO droplet formation is seen mainly in the gray state. Kinetic analysis both from time-lapse films and conventional microscopy, shows that increasing the concentration of DMSO prolongs the time spent in the gray state, decreases the time of initial appearance of droplet cells, and increases their subsequent rate of formation, without detectable effects on the rates of the remaining morphological transitions. DMSO also reduces the average rate of DNA synthesis and increases the average cell cycle time, particularly in the second (and subsequent) cell cycles after its addition. However, neither droplet nor doming cells are terminally differentiated. Thus a linear sequence of morphological states exists between the Rama 25 stem cells and the alveolar-like or more probably alveolar bud cells in vitro, and DMSO accelerates the overall conversion predominantly by truncating one of the steps in this pathway.

The effect of ionophores and related agents on the induction of doming in a rat mammary epithelial cell line.

Addition of dimethyl sulfoxide (DMSO) and the mammotropic hormones prolactin, hydrocortisone, insulin, and estradiol to confluent cultures of the epithelial cell line Rat Mammary (Rama) 25 increases dramatically the formation of domes in the cell monolayer after 48-72 hr. Associated with the increase in doming is an increase of 24% in the activity of the Na+/K+ ATPase. Both Ca2+ (A23187) and Na+ (monensin, gramicidin J, melittin) ionophores can replace DMSO in inducing domes, whilst the K+ ionophore valinomycin inhibits doming. However, there are no synergistic nor additive effects, respectively, with suboptimal or optimal concentrations of A23187 and melittin together. Ouabain, at concentrations which inhibit the Na/K ATPase in vitro, and amiloride, at concentrations reported to inhibit the passive transport of Na+, both inhibit completely the formation of domes induced by DMSO, A23187, and melittin. EGTA, however, inhibits only the induction of doming by DMSO and A23187; it is without effect with melittin. A23187 and melittin induce the major polypeptide changes that occur in doming cultures with DMSO, and most of these changes are also inhibited with ouabain. It is suggested that one possible interpretation of the findings is that the induction of doming by DMSO in Rama 25 cells occurs by means of sequential increases in Ca2+ and Na+ influxes into the cell, and that the increased intracellular concentration of Na+ so produced stimulates the Na+/K+ ATPase, with a net effect of pumping liquid beneath the cellular monolayer.

Isolation and properties of rat cell lines morphologically intermediate between cultured mammary epithelial and myoepithelial-like cells.

The cloned cuboidal epithelial cell line Rat Mammary (Rama) 25 converts at low frequency in culture to elongated cells that possess some of the properties of myoepithelial cells; one such clonal cell line is termed Rama 29. Three morphologically intermediate clonal cell lines have been isolated from Rama 25 which form a morphological series in the order: Rama 25 cuboidal cells, Rama 25-Intermediate 2(I2), Rama 25-I1, Rama 25-I4, and Rama 29 elongated cells. This same order is largely maintained for increasing percentages of elongated cells, decreasing percentages of cuboidal cells, decreasing tubular structures on collagen gels, and increasing times of appearance of tumors in nude mice. The fully elongated cells fail to revert to cuboidal cells and to form tumors. Binding of antisera to epithelial-specific milk fat globule membranes and human keratin declines whereas binding of antisera to myoepithelial-associated laminin, vimentin, and Thy-1 increases in the cell lines in the same order. Similarly 7 polypeptides characteristic of elongated cells increase and 4 polypeptides characteristic of cuboidal cells decrease in the cell lines in the same way. Anti-actin serum binds equally to all cell lines grown on plastic, except for Rama 25-I4, where its binding is increased. Rama 25-I1 and Rama 25-I4 cells also give rise to anti-actin, anti-myoglobin, and phosphotungstic acid hematoxylin-staining giant, striated cells on collagen gels and in tumors that also have ultrastructural characteristics of skeletal muscle. Fresh elongated converts of Rama 25 bind appreciably more anti-actin serum than many of the clonal elongated cell lines such as Rama 29. Ultrastructural analysis confirms the gradual loss of epithelial characteristics and the acquisition of immature myoepithelial characteristics in the same sequence of cell lines. It is suggested that such a linear sequence of intermediate morphological states occurs between the Rama 25 cuboidal cells and the elongated myoepithelial-like cells in vitro, and that a similar morphological sequence may exist in terminal ductal structures in vivo.

Improved MR venography: use of fast short inversion time inversion-recovery technique in evaluation of venous angiomas.

Eleven patients (five female and six male, aged 6-67 years) with venous angiomas underwent axial and coronal T1-weighted and fast short inversion time inversion-recovery (STIR) magnetic resonance (MR) imaging to assess the full extent of the malformations. Images were assessed subjectively by the authors in a nonblinded study. In all patients, fast STIR images depicted more anatomic detail than did T1-weighted images and depicted venous angiomas more clearly than did contrast material-enhanced CT scans but did not help discrimination of arteries and veins.