Three-year outcomes of intracapsular femoral neck fractures fixed with sliding hip screws in adults aged under sixty-five years.

INTRODUCTION: Intracapsular femoral neck fractures remain associated with high rates of post-traumatic femoral head necrosis, non-union, and revision surgery. AIM: Our aim was to identify factors associated with revision surgery in intracapsular femoral neck fractures treated with sliding hip screws (SHS) in adults aged <65 years. PATIENTS AND METHODS: Consecutive admissions were identified retrospectively from the Royal Victoria Hospital, Belfast, which was the largest volume hospital on the National Hip Fracture Database. Of 2201 hip fractures between 1st August 2008 and 31st December 2010, 97 (4%) intracapsular fractures treated with SHS in adults <65 years were followed for a mean of 2.9 years (range 0-6.6). RESULTS: Twenty-one (22%) hips were revised to arthroplasty. Avascular necrosis developed in 28 (29%) femoral heads. Eight (8%) fractures proceeded to non-union. Displaced fractures (p<0.001, Fisher's exact [FE]), posterior comminution (p=0.049, FE), chronic respiratory disease (p=0.006, FE) and residual distraction (p=0.011, χ2) were associated with revision to arthroplasty. Multiple regression found displaced fractures (p=0.006) and chronic respiratory disease (p=0.017) significant; in the latter 4 of 6 were revised (67%), including all four patients with chronic obstructive pulmonary disease (COPD). Eleven (11%) individuals required walking aids before injury, which rose to 34 (35%) at one year (p<0.0001, χ2). Eighty-nine (92%) individuals could walk alone outdoors before injury, but only 76 (78%) at one year (p=0.009, χ2). CONCLUSIONS: Displaced fractures in individuals with chronic respiratory disease should be considered high risk for revision to arthroplasty. Posterior cortex deficiency should be evaluated prior to choice of operation. Fracture biology and revascularisation play a greater role than operation timing. A significant proportion of individuals do not recovery pre-morbid mobility by one year.

Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life.

PURPOSE: Chemotherapy for non-small-cell lung cancer (NSCLC) remains controversial. We describe the two largest reported, randomized, parallel trials designed to determine whether the addition of chemotherapy influences duration and quality of life in localized, unresectable (mitomycin, ifosfamide, cisplatin [MIC]1 trial) and extensive (MIC2 trial) disease. PATIENTS AND METHODS: Ambulatory patients with NSCLC, aged 75 years or younger, with localized disease, were randomized in MIC1 to receive up to four cycles of chemotherapy (CT: mitomycin 6 mg/m(2), ifosfamide 3 g/m(2), and cisplatin 50 mg/m(2)) every 21 days, followed by radical radiotherapy (CT + RT) or radiotherapy (RT) alone. Extensive-stage patients were randomized in MIC2 to identical chemotherapy plus palliative care (CT + PC) or palliative care (PC) alone. Short-term change in quality of life (QOL) was assessed in a subgroup of patients. Data from the two trials were combined to allow multivariate and stratified survival analyses. RESULTS: Seven hundred ninety-seven eligible patients were randomized, 446 in MIC1 and 351 in MIC2. MIC CT improved survival in both trials (significantly in MIC2). The median survival time in MIC1 was 11.7 months (CT + RT) versus 9.7 months (RT alone) (P =.14); whereas in MIC2, median survival time was 6.7 months (CT + PC) compared with 4. 8 months (PC alone) (P =.03). QOL, assessed in 134 patients from start of trial to week 6, showed improvement with chemotherapy and deterioration with standard treatment. In the combined analysis of 797 randomized patients, the positive effect of MIC on survival was significant overall (P =.01) and after adjusting for prognostic factors (P =.01). CONCLUSION: MIC chemotherapy prolongs survival in unresectable NSCLC without compromising QOL.

Sputum and pulmonary function in asthma.

STUDY OBJECTIVE: To assess the relevance of sputum production to pulmonary function, in particular, persistent obstruction in patients with a primary clinical diagnosis of asthma. DESIGN: Cross-sectional study of all patients currently followed up in secondary care in a defined locality. SETTING: National Health Service and private clinics in north-east England. PATIENTS: All attenders, aged 18 years or older, with asthma, confirmed by reversibility of peak expiratory flow (PEF) by > or =15% and to > or =200 L/min. INTERVENTIONS: Pro forma history. Pulmonary function at attendance. Assessment of best function according to protocol. Measurement of actual FEV1, FVC, and PEF at attendance. MEASUREMENTS AND RESULTS: We studied 772 subjects; 387 (50%) were male; mean age was 55 years; atopic, 51%; current smokers, 11.5%; ex-smokers, 36%; and never smokers, 52.5%. Best pulmonary function was lower in chronic sputum producers (PEF, 83.2 vs 95.8; FVC, 67.9 vs 81.7% predicted). Chronic sputum production and its negative relationship with best function was strongly associated with smoking. There was little relationship between chronic sputum and persistent obstruction in nonsmokers. There were no univariate associations between sputum during attacks, or its color, and pulmonary function, but after allowing for demographic factors, including smoking, green sputum was associated with persistent obstruction. There was little relationship between sputum and actual/best function at attendance. CONCLUSIONS: Chronic sputum production is associated with persistent obstruction principally in those who have smoked, suggesting that the association reflects smoking rather than asthma. There is no interaction with atopy. After allowance for cigarette smoking, there is an association between green sputum production during exacerbations and persistent obstruction. Green sputum during relapse in asthma may indicate inflammation that is relevant to prognosis.

Plasma "cortisol" levels in right and left ventricular failure.

Plasma ;cortisol' values are reported in 36 patients during or following right ventricular failure, and 12 during or following left ventricular failure. In patients with right ventricular failure the normal circadian rhythm was abolished with elevation of midnight values. Disturbance of rhythm was less marked in left ventricular failure, although midnight values were usually raised. Dexamethasone suppression of plasma ;cortisol' levels was abolished or reduced in right ventricular failure. These results confirm our earlier findings and further support our contention that the disturbance of circadian rhythm is not due to a simple stress mechanism. The results are of importance in the differential diagnosis of Cushing's syndrome based on plasma ;cortisol' values, if there is concomitant right ventricular failure.

WE-14, a chromogranin a-derived neuropeptide.

The neuropeptide WE-14 is derived from the posttranslational processing of chromogranin A (CgA). While CgA is expressed in a preponderance of neuroendocrine cells, WE-14 is generated in a distinct subpopulation of CgA-immunopositive cells, most notably in the adrenal, pituitary, and parathyroid glands. Physiological and pharmacological studies have demonstrated that CgA is cleaved to generate WE-14 in the adrenal chromaffin cell population and in the enterochromaffin-like (ECL) cells of the oxyntic mucosa. Pathological analyses of neuroendocrine tumors have revealed a heterogeneous pattern of WE-14 immunostaining, with variable concentrations quantified and chromatographically resolved in tissue extracts. Phylogenetic surveys have demonstrated that WE-14 exhibits an ancient lineage, while ontogenetic examination has shown that it is generated at an early stage during fetal development. Putative WE-14 receptor binding sites have been identified in several tissues; however, the physiological role of WE-14 remains enigmatic.

In vitro characterization of porcine hepatocyte function.

The clinical consequences of acute liver failure are associated with high mortality. Intensive medical intervention is required to treat the symptoms of liver failure, including coagulopathy, metabolic instability, and encephalopathy. Providing temporary liver support with an extracorporeal liver assist device could stabilize the patient until a donor liver became available or the patient's own liver was able to recover. The use of human hepatocytes as the biologic component of the assist device is precluded by the scarcity of available tissue and the limited proliferative potential of adult hepatocytes in vitro. Consequently, porcine hepatocytes are being evaluated as a cell source for liver assist devices. Maintaining differentiated function in isolated hepatocytes, however, remains a challenge in the development of this technology and is complicated by the fact that the key therapeutic functions for short-term survival have not been well defined. Several approaches have been effective in prolonging rodent hepatocyte function in vitro, including manipulation of extracellular matrix. Here, we have investigated porcine hepatocyte function in vitro with a specific emphasis on the response to exogenous collagen matrix. In control cultures, albumin secretion increased during the first 7-10 days of culture to an average of 50 +/- 17 microg/day/10(6) cells and then decreased over the next 2 weeks. The pattern of urea synthesis was slightly different in that it was highest in the first 1-3 days postisolation (140 +/- 19 microg/day/10(6) cells) and then decreased by about 50% to a plateau level that was stable during the next 3-4 weeks of culture. Cytochrome P450-mediated activities were the most labile with time in culture and were undetectable after the first week in the absence of pharmacological inducers. In contrast to results reported for rat cells, porcine hepatocytes exhibited differentiated function in the absence of any modification of the culture dish surface and function was not increased or prolonged in the presence of exogenous collagen.

The effect of coculture with nonparenchymal cells on porcine hepatocyte function.

Porcine hepatocytes are currently being investigated as a therapy for patients suffering from acute liver failure. Incorporating hepatocytes in an extracorporeal device that would stabilize a patient until transplantation or recovery could dramatically decrease the mortality rate associated with this disease. The ability to maximize hepatocyte function would contribute significantly to being able to provide the required cell mass in a device of reasonable size. Several approaches have been effective at increasing rat hepatocyte function in vitro, including coculture with nonparenchymal cells. In this study, we investigated the effect of the addition of 3T3 cells to porcine hepatocyte culture and found that while there was an increase in albumin secretion, there was little or no effect on urea synthesis or cytochrome P450 activity.

A simple radiographic scoring method for monitoring pulmonary sarcoidosis: relations between radiographic scores, dyspnoea grade and respiratory function in the British Thoracic Society Study of Long-Term Corticosteroid Treatment.

BACKGROUND: We used a simple semi-quantitative radiographic scoring system for a controlled prospective study of long term corticosteroids in pulmonary sarcoidosis, conducted by the British Thoracic Society. METHODS: Radiographic opacities were described in 4 categories: reticulo-nodular shadows [R], mass opacities [M], confluence [C], and shadows associated with possible pulmonary fibrosis [F]. The extent of each type was scored on a 0-4 scale by quartiles, and profusion by a 0-4 scale as absent, minimal (just perceptible), mild moderate or gross. Combined scores for each film were derived by multiplying the extent and profusion for each type of opacity. In the study 149 patients were examined at entry and periodically over a 5-year period. Using the whole study population we examined the relationship between the radiographic scores for extent and profusion, how predominant types change with time and how the scores correlated with other indices of disease severity. RESULTS: R was the predominant abnormality throughout the study with a strong correlation between extent and profusion. Significant correlations in the expected directions were demonstrated between the R and F scores and a dyspnoea score, spirometry and TLCO, both at study entry, after 6 months and after 5 years. Similarly, there were significant relations between changes in spirometry and TLCO over five years and changes in R and F Scores. CONCLUSION: This scoring system would seem to be suitable, perhaps after further validation work, for other prospective clinical studies.

The relationship between work done and pulmonary function; validation of a method.

A two-stage bicycle exercise test with logarithmic intervals of load has been described, and the results reported in 760 patients. The test is now validated in a second group of 553 subjects. Performance data and FEV1 were available in all subjects and forced vital capacity in 366 of them. Regression equations of pulmonary function on work done stratified by sex and age were similar to those previously reported. Multiple regression showed that more than 57.8% of the variance could be explained in terms of vital capacity, height and age, with small contributions from weight and sex; with more than half being accounted for by vital capacity alone (R2 = 0.53). In an alternative equation predicted vital capacity, age (independently), percentage deficit of vital capacity below predicted, sex and weight/height2 explained 58.7% of the variance. In this approach, the percentage of vital capacity below predicted accounts for 25% of the variance after allowance for predicted vital capacity. It is confirmed that the first logarithmic stage of the test predicts a work rate that can be maintained for more than 5 minutes, producing a pulse rate of greater than 130 in two-thirds of the subjects. As the majority of those who failed to achieve this work rate had poor pulmonary function and were elderly, it is recommended that the second phase is set at a lower work load for these subjects.

Symptoms and pulmonary function in asthma.

The relationship between symptoms and pulmonary function in asthma is important if the latter is to be held relevant to management guidelines and their audit. Associations between reported symptoms, pulmonary function and therapy were studied in 824 asthmatics (mean FEV1 75.4% predicted; best FEV1 84.6% predicted; and actual/best peak flow (PEF) 87.5%). Bronchodilator usage (reflecting symptomatic wheeze) was evenly distributed up to eight times daily; 22.5% of subjects had nocturnal disturbance and 46.3% persistent daytime symptoms. The univariate relationships between symptoms and function were generally closer with best rather than actual/best. They were further explored using quintiles of function. Symptoms were consistently less as best function increased, but were highly significantly greater in the fifth than in the third and fourth quintiles of actual/best FEV1. There was a trend to a similar U-shaped relationship of actual/best PEF with nocturnal disturbance and daytime symptoms. Best function is a good determinant of expected symptom load in an asthmatic population. Below 85% actual/best function reflects the prevalence of symptoms. In asymptomatic patients a level of at least 85-90% is a useful check of physiological control but will not exclude some symptomatic patients, irrespective of best function.

The Darlington and Northallerton Prospective Asthma Study: best function predicts mortality during the first 10 years.

The Darlington/Northallerton prospective study of asthmatics referred to secondary care started in 1983, with review and new entry at 5-yr intervals. The principal outcome measures are: mortality (presented here), best function and therapeutic step. All adult asthmatics with > or = 15% peak flow (PEF) reversibility to > or = 200 l min-1 were included. Socio-demographic variables, PEF and spirometry were recorded prospectively. Best vital capacity (FVC) and PEF were assessed according to protocol. The mortality of the original cohort after 10 yr was expressed as standardized mortality ratio (SMR) against the local population, with history and pulmonary function at entry as explanatory variables. Ninety-five per cent follow-up was achieved in 628 subjects, with 173 deaths (29.1% of those traced). The excess death rate was nearly 50% (SMR 1.47, 95% CI 1.26-1.71), with 56% of deaths due to respiratory disease (expected 10%). After allowance for age and sex, there was a consistent inverse relationship between mortality and entry best FVC, increased risk of death 1.51 (95% CI 1.33-1.72) per 10% deficit of best FVC predicted. The risk of respiratory death was eight times greater, and of non-respiratory death three times greater, in the lowest compared with the highest quartile of best FVC. There were no interactions with smoking, but possible enhancement of the effect in the socially deprived. Best FVC was a particularly powerful predictor of mortality in subjects < 65 years at entry, in whom 64% of the excess deaths occurred. Most of the excess in respiratory deaths was not due to acute severe asthma but to the development of chronic obstructive pulmonary disease (COPD), as defined functionally, irrespective of smoking habit which made no further contribution to mortality.

Actual over best function as an outcome measure in asthma.

Several guidelines for the management of asthma suggest that actual/best function is a useful outcome measure. This implies accurate assessment of best function, and a standard for the proportion of best function to be achieved. Seventeen clinics observed their practice simultaneously during four periods in 1990. The aims of the study included testing a protocol for the assessment of best function, and validating actual/best function as an outcome measure. The proposed target for actual/best function to indicate satisfactory control was 80%. The protocol for assessment of best function required formal trial of steroids if best function was < 70% predicted; with regular recording of peak expiratory flow (PEF) if < 80% predicted. PEF was recorded in 515 and FEV1 in 680 of 767 subjects, following the usual clinic practice. If the protocol for best function was not satisfied, mean actual/best function was no higher than if it was, except when best PEF was < 70% predicted. This suggests the need for a PEF chart in these latter patients. Best function was greater in females than males, but actual/best function was almost identical. Whilst best function declined with increasing intensity of treatment, actual/best function was almost independent of regimen step, particularly in the centre which most closely adhered to the protocol. These results confirm that actual/best function is a valid outcome measure. Mean actual/best was > 80% except for FEV1 in two centres. It is suggested that the target in chronic management of asthma is raised from 80 to 85% of best, when actual/best PEF is used as a spot check in patients believed to be on optimal therapy.

Controlled-release theophylline in the treatment of nocturnal asthma.

A total of 104 asthmatic patients with symptoms of asthma and/or a 'morning dip' in the peak expiratory flow rate (PEFR) who were receiving multiple therapies, including inhaled or oral steroids, were treated in addition once nightly with controlled-release theophylline in an 8-week double-blind, placebo-controlled cross-over study. Theophylline produced an improvement in symptoms of cough, wheeze, sleep disturbance and PEFR in the 73 completing patients compared to run-in and placebo treatment. Theophylline also produced an improvement in the forced expiratory volume in 1 s and forced vital capacity relative to baseline, and in the difference between actual and predicted PEFR values. Nausea was the most frequent side-effect but both patients' and investigator's global impressions of the effect of study medication were in favour of theophylline.