The effect of time to surgery on outcomes and complication rates following total hip arthroplasty for fractured neck of femur.

INTRODUCTION: Total hip arthroplasty is recommended for elderly patients with fractured neck of femur who are independently mobile, have few co-morbidities and are not cognitively impaired. Providing a daily total hip arthroplasty service is challenging for some units in the UK and considering that these patients may be physiologically distinct from the average hip fracture patient, loss of the best practice tariff as a result of surgical delay may be unjustified. The aim of this study was to determine whether time to surgical intervention for patients eligible for total hip arthroplasty had a negative impact on patient complications, length of stay and functional outcomes. METHODS: All patients undergoing total hip arthroplasty for fractured neck of femur at our institution over a ten-year period were identified. Complications and functional outcomes were compared between patients receiving total hip arthroplasty before and after 36 hours. RESULTS: Of 112 consecutive patients undergoing total hip arthroplasty, 70 responded to a questionnaire or telephone consultation. Four patients were excluded owing to delayed presentation, the presence of advanced rheumatoid arthritis or a pathological fracture. Two-thirds (64%) of the remaining 66 patients underwent surgery within 36 hours of presentation. There were no significant differences between the groups of patients receiving surgery before or after 36 hours with regard to postoperative length of stay, complications, Oxford hip scores or visual analogue scale scores for state of health. CONCLUSIONS: Delaying surgery for patients eligible for total hip arthroplasty as per the National Institute for Health and Care Excellence guidelines is justified and should not incur loss of the best practice tariff.

Clinical outcome following primary total hip or knee replacement in nonagenarians.

Introduction The Elective Orthopaedic Centre in Epsom has an established patient reported outcome measures programme, into which all patients are enrolled. Postoperative complications, Oxford hip/knee scores (OHS/OKS) and EQ-5D™ (EuroQol, Rotterdam, Netherlands) scores are collected up to the second postoperative year. Our population is ageing and the number of joint replacements being performed on the very elderly is rising. The aim of this study was to investigate the outcome of joint replacements in a nonagenarian population. Methods Our dataset was reviewed retrospectively for a cohort of nonagenarians undergoing either a primary total hip replacement (THR) or total knee replacement (TKR) between April 2008 and October 2011. Postoperative complications, mortality rates and functional outcomes were compared with those of a time matched 70-79-year-old cohort. Results Nonagenarians requiring a THR presented with a lower preoperative OHS (p=0.020) but made a greater improvement in the first postoperative year than the younger cohort (p=0.040). The preoperative OKS was lower for nonagenarians than for the control group (p=0.022). At one and two years after TKR, however, there was no significant difference between the age groups. The nonagenarians had a greater risk of requiring a blood transfusion following both THR (p=0.027; 95% confidence interval [CI]: 1.11-5.75) and TKR (p=0.037; 95% CI: 1.08-16.65) while the latter cohort also required a longer stay than their younger counterparts (p=0.001). Mortality rates were higher in the nonagenarian group but these were in keeping with the life expectancy projections identified by the Office for National Statistics. Conclusions Over a two-year period, the functional outcome and satisfaction rates achieved by nonagenarians following a THR or TKR are comparable with 70-79-year-olds.

Performance and persistence of a blood pressure self-management intervention: telemonitoring and self-management in hypertension (TASMINH2) trial.

This study aimed to evaluate, in detail, the implementation of the self-management intervention used in the TASMINH2 trial. The intervention, comprising self-monitoring for the first week of each month and an individualised treatment self-titration schedule, was developed from a previous trial of self-management. Two hundred and sixty-three patients with poorly controlled but treated hypertension were randomised to receive this intervention and underwent training over two or three sessions. Participants were followed up for 12 months during which time process data were collected regarding the persistence and fidelity of actual behaviour compared with intervention recommendations. Two hundred and forty-one (92%) patients completed training of whom 188 (72%) self-managed their BP and completed at least 90% of expected self-monitoring measurements for the full year of the study. Overall, 268/483 (55%) of recommended medication changes were implemented. Only 25 (13%) patients had controlled BP throughout the year and so were not recommended any medication changes. Adherence to the protocol reduced over time as the number of potential changes increased. Of those self-managing throughout, 131 (70%) made at least one medication change, with 77 (41%) implementing all their recommended changes. In conclusion, self-management of hypertension was possible in practice with most participants making at least one medication change. Although adherence to the intervention reduced over time, implementation of treatment recommendations appeared better than equivalent trials using physician titration. Future self-management interventions should aim to better support patients' decision making, perhaps through enhanced use of technology.

Self-monitoring in hypertension: a web-based survey of primary care physicians.

Although self-monitoring of blood pressure is common among people with hypertension, little is known about how general practitioners (GPs) use such readings. This survey aimed to ascertain current views and practice on self-monitoring of UK primary care physicians. An internet-based survey of UK GPs was undertaken using a provider of internet services to UK doctors. The hyperlink to the survey was opened by 928 doctors, and 625 (67%) GPs completed the questionnaire. Of them, 557 (90%) reported having patients who self-monitor, 191 (34%) had a monitor that they lend to patients, 171 (31%) provided training in self-monitoring for their patients and 52 (9%) offered training to other GPs. Three hundred and sixty-seven GPs (66%) recommended at least two readings per day, and 416 (75%) recommended at least 4 days of monitoring at a time. One hundred and eighty (32%) adjusted self-monitored readings to take account of lower pressures in out-of-office settings, and 10/5 mm Hg was the most common adjustment factor used. Self-monitoring of blood pressure was widespread among the patients of responding GPs. Although the majority used appropriate schedules of measurement, some GPs suggested much more frequent home measurements than usual. Further, interpretation of home blood pressure was suboptimal, with only a minority recognising that values for diagnosis and on-treatment target are lower than those for clinic measurement. Subsequent national guidance may improve this situation but will require adequate implementation.

Escalating-dose HLA-mismatched DLI is safe for the treatment of leukaemia relapse following alemtuzumab-based myeloablative allo-SCT.

Although the feasibility of using HLA-mismatched unrelated donors as an alternate graft source for haematopoietic SCT (HSCT) has been shown, little is known about the safety of HLA-mismatched DLI for the treatment of relapse. We examined the outcome of 58 consecutive leukaemia patients who received escalating-dose DLI for treatment of relapse after alemtuzumab-conditioned myeloablative unrelated donor HSCT at our institution. High-resolution HLA typing on stored DNA samples revealed mismatches in 28/58 patients who were considered HLA-matched at the time of transplantation. Following DLI from HLA-matched (10/10) (n=30) or -mismatched (7-9/10) (n=28) unrelated donors, we found no significant difference in the incidence of acute GVHD (17.2% versus 23.1%, P=0.59), probability of remission at 3 years (62.1% versus 63.9%, P=0.89) or 5-year OS (89.8% versus 77.7%, P=0.22). We conclude that escalating-dose DLI can be safely given to HLA-mismatched recipients following T-depleted myeloablative HSCT.

First aid for obstetric haemorrhage: the pilot study of the non-pneumatic anti-shock garment in Egypt.

OBJECTIVE: To compare the effect of non-pneumatic anti-shock garment (NASG) on blood loss from obstetric haemorrhage with standard management of obstetric haemorrhage. DESIGN: Observational study of consecutive obstetric haemorrhage cases before and after introduction of the NASG. SETTING: Four tertiary care maternity facilities in Egypt. SAMPLE: The sample consisted of women with obstetric haemorrhage and signs of shock and the entry criteria were: >750 mL of blood loss and either pulse of >100 beats per minute or systolic blood pressure of <100 mmHg. A total of 158 women were in the preintervention group and 206 in the postintervention group. METHODS: All the women with haemorrhage meeting the eligibility criteria were treated according to the standard protocol for 4 months (May-August 2004); blood loss was measured and recorded. The NASG was then introduced, and all the women meeting the eligibility criteria were treated according to the standard haemorrhage protocol plus the NASG for 4 months (September-December 2004). MAIN OUTCOME MEASURES: Measured blood loss collected in a closed-end, graduated, plastic, under buttocks collection drape. RESULTS: Median measured blood loss in the drape following study entry was 50% lower in those treated with the NASG (250 versus 500 mL, P < 0.001). There was also a non-statistically significant decrease in morbidity and mortality. CONCLUSIONS: This is the first comparative study of the NASG with a standard obstetric haemorrhage treatment protocol. The NASG shows promise for management of obstetric haemorrhage, particularly in lower resource settings. Larger studies will be needed to determine if the NASG contributes to statistically significant decreases in morbidity and mortality.

Altered rheology of lymphocytes in the diabetic mouse.

AIMS/HYPOTHESIS: Clinical complications associated with diabetes may be related to altered physical properties of leucocytes. We used micropipette techniques to examine leucocyte rheology (specifically lymphocyte rheology) in the non-obese diabetic (NOD) mouse model of diabetes mellitus. We hypothesised that diabetes affects lymphocyte rheology, and specifically that lymphocyte membranes from diabetic mammals have a higher cortical tension than those from non-diabetic mammals. METHODS: Lymphocytes were isolated from diabetic and control mice. Lymphocyte deformation and activation were assessed with a micropipette apparatus. Cellular activation was assessed visually. Projection length into the micropipette during aspiration was used to calculate the viscosity of the cell. Recovery length following expulsion from the micropipette was used to derive the recovery time constant, which is the ratio of cortical tension : viscosity (T(o)/mu) for each cell. The cell cortical/surface tension was calculated from this ratio. RESULTS: Of 692 control lymphocytes, 29% were spontaneously activated compared with 39% of 624 diabetic cells (p<0.06) and 31.5% of 315 non-diabetic NOD cells (p=0.14). Viscosity values for diabetic lymphocytes were equivalent to those for control cells (1345.12+/-1420.97 Pa.s vs 996.84+/-585.07 Pa.s, p=0.13). The average T(o)/micro value for diabetic lymphocytes (35.4+/-16.5x10(-6) cm/s) was significantly higher than that for control cells (24.8+/-11.3x10(-6) cm/s, p<0.03) and cells from non-diabetic NOD mice (26.3+/-9.0x10(-6) cm/s, p<0.005). The mean cortical tension values for diabetic and control cells were 4.7+/-2.3x10(-4) N/m and 2.8+/-0.7x10(-4) N/m respectively (p<0.003). CONCLUSIONS/INTERPRETATION: Lymphocytes from diabetic mice tend to spontaneously activate. They have an equivalent cytoplasmic viscosity but a larger recovery time constant compared with cells from control mice. The results suggest that diabetic lymphocytes are stiffer than control cells.

Abscisic acid regulation of gene expression during water-deficit stress in the era of the Arabidopsis genome.

Changes in gene expression may lead to cellular adaptation of water-deficit stress, yet all of the induced mRNAs may not play this role. Changes in gene expression must be signalled by transduction mechanisms that first sense a water deficit. This first step triggers changes in gene expression that function to synthesize additional signals such as abscisic acid (ABA). The enzymes involved in ABA biosynthesis have been cloned and their regulation during water-deficit stress is being characterized. Once ABA levels are increased, further signalling mechanisms are initiated to signal new gene expression patterns that are proposed to play a role in cellular adaptation to water-deficit stress. As the genome of Arabidopsis is now completed, much more information can be exploited to characterize these responses.

Treatment of late-onset tibia vara using afghan percutaneous osteotomy and orthofix external fixation.

The Afghan osteotomy was combined with external fixation on 19 patients (23 extremities) with late-onset tibia vara. The average weight was 258 lb and all patients weighed >95th percentile. The average preoperative deformity was 28.2 degrees. The average intraoperative correction was 27.6 degrees. Average healing time was 141 days. The mean follow-up was 2.7 years. Based on radiographic correction, at long-term follow-up, there were 15 excellent, two fair, and six poor results. The quality of the initial correction was the only significant variable, and it was borderline (p = 0.0587). Complications included loss of alignment, peroneal nerve palsy, superficial pin tract infection, deep infection, and fracture. This method offers a technically simple procedure with a relatively low complication rate. It allows early mobilization and provides the ability to manipulate the correction postoperatively. An excellent long-term outcome is predicated on achieving an acceptable initial correction as determined by intraoperative mechanical axis radiographs.

The H1 histone variant of tomato, H1-S, is targeted to the nucleus and accumulates in chromatin in response to water-deficit stress.

Water deficit has a significant impact on patterns of gene expression. Based on the deduced amino acid sequence, it has been proposed that the drought and abscisic acid-induced gene (his1-s) of tomato (Lycopersicon esculentum Mill.) encodes an H1 histone variant. To study the role of H1-S it is important to understand the expression characteristics of the protein. To identify the his1-s product in vivo the his1-s cDNA was fused to a (His)6 tag and overexpressed in Escherichia coli. The H1-S fusion protein was used to generate an antibody that recognized a protein with an apparent molecular weight of 31 kDa that accumulates in response to water deficit in the whole plant and detached leaves. A time course of his1-s expression showed that protein accumulation is delayed compared to the mRNA accumulation in both the whole plant and detached leaves. Cellular fractionation, immunofluorescence and H1-S::beta-glucuronidase fusion analyses in transgenic tissues were used to determine the cellular localization of H1-S. The results showed that H1-S accumulates in nuclei and is associated with chromatin of wilted tomato leaves. The drought- and abscisic acid-induced gene his1-s encodes a linker-histone subtype specifically accumulated in the nuclei and chromatin of tomato leaves subjected to water-deficit conditions. Although the molecular mechanism of H1-S function is still unclear, the expression characteristics of H1-S are consistent with a potential role of this protein in the regulation of gene expression in response to water deficit.

Recent advances in the treatment and outcome of locally advanced rectal cancer.

OBJECTIVE: To compare the outcomes of treatment of locally advanced rectal cancer of the early era (1975-1990) with those of the late era (1991-1997). BACKGROUND: Preoperative therapy has been used in locally advanced rectal cancer to preserve sphincter function, decrease local recurrence, and improve survival. At the University of Florida, preoperative radiation has been used since 1975, and it was combined with chemotherapy beginning in 1991. METHODS: The records of 328 patients who underwent preoperative radiation or chemoradiation followed by complete resection for locally advanced rectal cancer defined as tethered, annular, or fixed tumors were reviewed. The clinicopathologic characteristics, adjuvant treatment administered, surgical procedures performed, and local recurrence-free and overall survival rates were analyzed. RESULTS: There were 219 patients in the early era and 109 in the late era. No significant differences were seen in patients (age, gender, race) or tumor characteristics (mean distance from the anal verge, annularity, fixation). Preoperative radiation regimens were radiobiologically comparable. No patient in the early era received preoperative chemotherapy, compared with 64 in the late era. Of those receiving any pre- or postoperative chemotherapy, three patients received chemotherapy in the early era, compared with 76 in the late era. Sphincter-preserving procedures increased from 13% in the early era to 52% in the late era. Pathologic downstaging for depth of invasion increased from 42% to 58%, but lymph node negativity remained similar. The 1-, 3-, and 5-year local recurrence-free survival rates were comparable. However, in the late era, 1-, 3-, and 5-year overall survival rates improved significantly compared with those of the early era, and also compared with each of the preceding 5-year intervals. CONCLUSION: The addition of a chemotherapy regimen to preoperative radiation therapy improves survival over radiation therapy alone. Likewise, an improvement in downstaging is associated with an increase in sphincter-preserving procedures.

Surgical management of ankle valgus in children: use of a transphyseal medial malleolar screw.

Valgus deformity of the ankle in children is associated with a wide variety of clinical conditions. A retrospective review was performed of 17 children (29 involved extremities) with ankle valgus deformity who had been managed by use of a percutaneously placed, transphyseal medial malleolar screw. Median age at the time of surgery was 11 years, 2 months. Median postoperative follow-up was 2 years, 2 months. Tibiotalar axis and ankle mechanical axis were the best radiographic indicators of ankle valgus deformity. Fibular station and epiphyseal wedging were poor predictors of ankle alignment. Significant improvement in the tibiotalar axis (median, 12 degrees) was noted at follow-up, and the median rate of correction was 0.59 degree/month. Resumption of physeal growth and recurrence of deformity (rate of 0.60 degree/month) was seen when the screws were removed before skeletal maturity. The transphyseal medial malleolar screw is a minimally invasive, minimally morbid, technically simple method of reversible partial epiphysiodesis at the ankle and is an effective technique for the correction of ankle valgus deformity associated with a wide variety of clinical conditions in children.

A simplified and rapid procedure for in situ hybridization on human, flash-frozen, post-mortem brain and its combination with immunohistochemistry.

A simplified and rapid method is described for in situ hybridization (ISHH) studies of human post-mortem brain. Brain tissue was dissected into slices and was flash-frozen at -70 degrees C for storage. ISHH was carried out on 12 microns cryostat sections, post-fixed in 4% paraformaldehyde. The histology of human brain tissue prepared by this technique rivalled that of formalin-fixed, wax-embedded tissue. In ISHH studies, flash-frozen tissue gave superior results to those obtained following long-term fixation of tissue in 10% formalin with subsequent wax-embedding, or short-term prefixation in 4% paraformaldehyde. A systematic evaluation of commonly employed preparative procedures for ISHH was carried out on flash-frozen brain and a simplified protocol, consisting only of fixation and dehydration, was developed as a result of these studies. Specific hybridization of probes to a number of mRNA species was demonstrable in neurons in different brain regions. Using 0.5% glutaraldehyde/4% paraformaldehyde post-fixation, immunohistochemical labelling of TH-positive cortical catecholaminergic neurons and striatal dopaminergic terminals was successfully demonstrated in flash-frozen tissue. The same fixation technique also allowed combination of ISHH and immunohistochemistry for the simultaneous demonstration of tyrosine hydroxylase mRNA and peptide in neurons of human brain stem and cortex. mRNA and peptides in flash-frozen tissue were found to be stable for more than 3 years. ISHH could be readily performed on relatively large brain structures. In addition to permitting excellent ISHH and immunohistochemistry, alone or in combination, flash-freezing allows the maximum versatility of tissue use and does not compromise its study by other neuroscience techniques.

The interaction of light and abscisic acid in the regulation of plant gene expression.

Extended dark treatments of light-grown plants of both Lemna gibba and Arabidopsis thaliana resulted in substantial increases in abscisic acid (ABA) concentrations. The concentration of ABA could be negatively regulated by phytochrome action in Lemna. As has been noted in other species, ABA treatment reduced Lemna rbcS and Lhcb RNA levels, which are positively regulated by phytochrome in many species. In view of these observations, the possibility that phytochrome effects on gene expression may be mediated primarily by changes in ABA was tested using a transient assay in intact plants. The phytochrome responsiveness of the Lemna Lhcb2*1 promoter was still apparent in the presence of exogenous ABA. Additionally, when 2-bp mutations were introduced into this promoter so that phytochrome responsiveness was lost, a response to exogenous ABA was still present. We conclude that phytochrome- and ABA-response elements are separable in the Lhcb2*1 promoter. We tested whether the effects of ABA on RNA abundance could be inhibited by treatment with gibberellin and found no evidence for such an inhibition. We have also found that the ABA-responsive Em promoter of wheat can be negatively regulated by phytochrome action. It is likely that this regulation is mediated at least in part by phytochrome-induced changes in ABA levels. Our results demonstrate that it is essential to take into account that dark treatments and the phytochrome system can affect ABA levels when interpreting studies of light-regulated genes.

A lea-class gene of tomato confers salt and freezing tolerance when expressed in Saccharomyces cerevisiae.

During periods of water deficit, plants accumulate late embryogenesis-abundant (LEA) proteins which are thought to protect cells from stresses associated with dehydration. One of these genes, le25, is expressed in tomato leaves and roots in response to water deficit and abscisic acid accumulation. To study the function of this protein and to test the effect of overproduction of the LE25 protein in Saccharomyces cerevisiae (Sc), a recombinant plasmid in which le25 is expressed under the control of the GAL1 promoter was constructed. The content of LE25 was high in Sc cells transformed with the recombinant plasmid. The transformant exhibited several stress-tolerant phenotypes. Growth of the transformant in a medium with 1.2 M NaCl was improved, as compared to a control strain. While the control strain showed a long lag phase of 40 h, le25-expressing cells showed a shortened lag phase of 10 h. However, no growth improvement was observed in a medium with 2 M sorbitol. In addition, the transformant had an increased survival rate after freezing stress, but not after high-temperature stress. These results, together with its predicted secondary structure, may indicate that LE25 functions as an ion scavenger.

NPR genes, which are negatively regulated by phytochrome action in Lemna gibba L. G-3, can also be positively regulated by abscisic acid.

We have found that NPR1 and NPR2, two genes from Lemna gibba L. G-3 that can be negatively regulated by phytochrome action, can also be positively regulated by the plant hormone abscisic acid (ABA). Both genes were responsive to low concentrations of exogenous ABA; an increase in NPR1 RNA could be detected in response to concentrations as low as 10 nM. We have also tested phytochrome responsiveness of 5' promoter-deletion constructs of one of these genes, NPR1, in transient assays utilizing particle bombardment. This analysis demonstrated that DNA sequences important for phytochrome regulation are present downstream of -198 from the transcription start site. A response to ABA treatment could also be observed in the transient assay system. When intact plants were placed in darkness, there was an increase in ABA levels as well as increased levels of NPR1 and NPR2 RNA.

Characterization of Expression of Drought- and Abscisic Acid-Regulated Tomato Genes in the Drought-Resistant Species Lycopersicon pennellii.

A number of genes are induced by drought stress, and some of these genes are regulated by the plant hormone abscisic acid (ABA). In tomato (Lycopersicon esculentum), four genes have been identified and isolated that require elevated levels of endogenous ABA for expression: le4, le16, le20, and le25. To gain a better understanding of the role of these genes during stress, their expression has been studied in the drought-resistant relative of tomato, Lycopersicon pennellii. It was determined that homologous genes to all four of the L. esculentum genes were present in the L. pennellii genome. Studies were undertaken to compare the expression characteristics of these genes in L. esculentum, L. pennellii, and their F1. Using two methods of water-deficit imposition, whole plants to which water was withheld and detached leaves that were wilted to 88% of their original fresh weight, it was demonstrated that transcripts of these genes accumulated in L. pennellii in response to water deficit. In general, the increase occurred after a longer period of water deficit in L. pennellii than in tomato. As in drought-sensitive species, ABA levels were elevated by drought stress in L. pennellii, although the levels were reduced compared with those in tomato. All four tomato genes were responsive to ABA in L. esculentum and the F1, but only three of the four genes (le16, le20, and le25) were induced in response to exogenous application of ABA in L. pennellii. The patterns of expression of these genes in L. pennellii are generally similar to that of L esculentum; therefore, it is suggested that these genes play a similar, yet undefined, role in both genotypes rather than being genes that are responsible for the greater drought resistance of L. pennellii.