Late dislocation after total hip arthroplasty

Objectives: Instability after total hip arthroplasty is a troublesome complication. It commonly occurs in the first 3 postoperative months, but the risk continues over time.There are numerous treatment options, but they have relatively unpredictable outcomes. Numerous factors have been associated with dislocation, but research has mainly focused on the surgical ones. Epidemiological factors remain the subject of much debate.We aimed to establish the incidence of dislocation over time.     

The role of capillary density, macrophage infiltration and interstitial scarring in the pathogenesis of human chronic kidney disease

To assess the relationship between interstitial capillary density and interstitial macrophages we prospectively measured these factors in situ in 110 patients with chronic kidney disease. Macrophage numbers and urinary MCP-1/CCL2 levels significantly correlated inversely with capillary density which itself significantly correlated inversely with chronic damage and predicted disease progression. In 54 patients with less than 20% chronic damage, there was a significant correlation between the urinary albumin to creatinine ratio and MCP-1/CCL2, and MCP-1/CCL2 and macrophages but not between MCP-1/CCL2 and capillary density. Conversely, in 56 patients with over 20% chronic damage there was no correlation between MCP-1/CCL2 and macrophages but there were significant inverse correlations between capillary density and both macrophages and chronic damage. The expression of VEGF mRNA significantly correlated with macrophage infiltration, capillary density and chronic scarring. In an ischemic-hypertensive subgroup there was upregulation of the hypoxia marker carbonic anhydrase IX and with over 20% chronic damage an increased macrophage to CCR2 ratio. Our study shows that proteinuria and MCP-1/CCL2 are important for macrophage recruitment in early disease. As renal scarring evolves, alternative pathways relating to progressive tissue ischemia secondary to obliteration of the interstitial capillary bed predominate.     

On the fine structure and distribution of secretory cells in the supraoesophageal ganglion of the lugworm (Arenicola marina L.)

The ultrastructure of the brain in Arenicola has been investigated with special reference to secretory cells and processes. Electron-dense secretory granules (elementary granules) are found in neurones, both in the brain proper and in the neuroectodermal connectives. Based on differences in fine structure four categories of secretory neurones appear distinguishable: (i) large dorsal neurones with elementary granules < 1200 Å in mean diameter, probably containing nonpeptidergic secretion; (ii) equally large neuroectodermal cells with elementary granules > 1200 Å in mean diameter, which may contain peptidergic secretion; and (iii) two types of elongate or fusiform cells, which, in some cytological details, mimic either dorsal neurones or neuroectodermal cells; they contain, respectively, elementary granules < 1200 Å and > 1200 Å in mean diameter. The similarities which exist between the elongate cells and the two categories of larger neurones leave some doubt about their separate status. The neuroectodermal cells and the elongate cells with larger granules are confined to the subectodermal nervous tissue and the connectives. The majority of the processes of these cells terminate on the perineurium of the connectives. Dorsal neurones and their processes are chiefly confined to the brain proper. From previous experiments it is known that the maturation hormone produced by the brain is found only in the posterior half of the brain. The zonation of secretory cells and processes, described here, fails to match this known variation in hormone content. No obvious storage/release site has yet been detected, and it seems likely that hormone is released via terminals scattered over the perineurium.     

Localisation of a pulmonary autoantigen in cryptogenic fibrosing alveolitis.

BACKGROUND--Cryptogenic fibrosing alveolitis (CFA) is believed to have an immunological pathogenesis with a persisting inflammatory reaction to an as yet unidentified pulmonary antigen(s). A high frequency of IgG autoantibodies has previously been found in the plasma of patients with CFA to an extractable 70-90 kDa lung antigen by Western blotting. Preliminary immunohistochemical studies with patient IgG had indicated that the target protein(s) might be associated with alveolar epithelial lining cells which have previously been suggested as the site of immunological attack in CFA. METHODS--In order to confirm this finding immunohistochemical analysis and Western blotting were performed on a human type II alveolar cell line (A549) using CFA patient plasma. In order to study further the distribution of the antigen, antibodies were raised in a rabbit to the partially purified 70-90 kDa CFA lung protein. RESULTS--The results showed that the human CFA autoantibody recognised a 70-90 kDa protein with a cytoplasmic distribution present in the A549 cells, confirming previous observations. The immune rabbit IgG recognised a protein of similar molecular weight by Western blotting of protein derived from lung biopsy samples of patients with CFA and A549 cells. In addition it immunoprecipitated protein(s) of this molecular weight from lung biopsy protein extracts from patients with CFA. The precipitated protein(s) were found to cross-react with the autoantibody found in the plasma of patients with CFA. Immunohistochemical analysis with immunised rabbit antibody revealed positive staining of type I and II alveolar epithelial lining cells in CFA. A similar pattern of epithelial staining was also observed with the rabbit IgG on biopsy specimens of lung from patients with sarcoidosis and control lung tissue, although this was more focal and less intense. No positive staining was seen on sections from a number of non-pulmonary tissues (colon, liver, kidney, tonsil, lymph node, skin, cervix). Cytoplasmic staining of the A549 cell line was also detected. CONCLUSIONS--The 70-90 kDa protein recognised by autoantibodies in patients with CFA is associated with pulmonary epithelial lining cells. The immune rabbit IgG produced appears to recognise antigen by Western blotting and immunohistochemical staining of lung tissue in a similar pattern to the patient autoantibodies. Immunohistochemical data obtained with this antibody suggest that the putative autoantigen against which patients with CFA mount a humoral immune response may be endogenous and specific to the lung.     

Early changes in scores of chronic damage on transplant kidney protocol biopsies reflect donor characteristics,but not future graft function

The amount of irreversible injury on renal allograft biopsy predicts function, but little is known about the early evolution of this damage. In a single‐center cohort, we examined the relationship between donor‐, recipient‐, and transplantation‐associated factors and change in a morphometric index of chronic damage (ICD) between protocol biopsies performed at implantation and at 2–3 months. We then investigated whether early delta ICD predicted subsequent biochemical outcomes. We found little evidence to support differences between the study group, who had undergone serial biopsies, and a contemporaneous control group, who had not. In allografts with serial biopsies (n = 162), there was an increase in ICD between implantation (median: 2%, IQR:0–8) and 2–3 months post‐transplant (median 8% IQR:4–15; p < 0.0001). Donation from younger or live donors was independently associated with smaller early post‐transplant increases in ICD. There was no evidence for a difference in delta ICD between donation after cardiac death vs. donation after brain death, nor association with length of cold ischemia. After adjustment for GFR at the time of the second biopsy, delta ICD after three months did not predict allograft function at one yr. These findings suggest that graft damage develops shortly after transplantation and reflects donor factors, but does not predict future biochemical outcomes.     

Epithelial membrane antigen in normal and proteinuric glomeruli and in damaged proximal tubules

Epithelial membrane antigen was detected in normal glomeruli by a polyclonal antiserum to the antigen and by the monoclonal antibodies Ca 1, DAKO-EMA and HMFG 2, but not HMFG 1, using an indirect immunoperoxidase method. The antigen was in the form of a thin ring or collar at the junction of glomerulus and tubule. In a series of 47 renal biopsies from patients with proteinuria, the antigen could still be seen in glomeruli, provided that there were adequate numbers of glomeruli in the sections. The main object of study was the glomerular tip lesion, in which tip adhesions were seen to be just adjacent to the patch of epithelial membrane antigen. This suggested that the antigen may be important in pathogenesis of the lesion. Normal proximal tubules did not express epithelial membrane antigen but it was detected on the luminal border of acutely damaged proximal tubules. Thus the distribution of epithelial membrane antigen in the kidney is more complex than was previously thought.     

Induction of tolerance to a murine fibrosarcoma in two zones of dosage--the involvement of suppressor cells

Small size inocula (10(1)-10(3) cells) of cells from a syngeneic methylcholanthrene-induced fibrosarcoma (FSA) induced tolerance when injected s.c. into C3Hf mice. Mice were unable to respond to subsequent challenge with moderate, immunogenic doses of FSA. Tolerance was demonstrated in an in vivo transfer (Winn) assay and an in vitro tumour-specific TH cell assay. Low zone tolerance was associated with the presence of tumour-specific TS cells in the spleen. Moderate size inocula (10(4)-10(6) FSA cells) were immunogenic but larger cell doses (greater than 10(6)) were again tolerogenic. In the high zone, tolerance was associated with both tumour-specific TS cells and non T suppressor cells that were not tumour-specific. These results support the view that immunogenic tumours, as they grow from small cell numbers, might be able to escape host surveillance by specifically tolerizing the immune system. They also suggest that large tumour burdens can interfere with the host's immune response by inducing suppressor cells.     

Measuring quality in general practice. Pilot study of a needs,process and outcome measure.

1. As part of the Scottish Shadow Fundholding Evaluation (1990-92), quality of care was assessed in 6 practices with 49 general practitioners using a pre-consultation health needs questionnaire, consultation length as a process measure (previously shown to be a proxy measure for quality) and a post-consultation satisfaction/outcome measure which contained a subset of six questions assessing whether patients felt enabled by their consultation. This report describes secondary analysis of the available dataset undertaken to explore whether the approach used to evaluate quality of care for patients with specific clinical problems could be extended to the generality of general practice consultations. 2. Chapters 1 and 2 of the report describe earlier work developing both the concepts and instruments used in the Shadow Evaluation, and general findings already reported. The reliability and the construct validity of the measure of enablement are examined and found to be satisfactory. 3. Strong correlations between more time at consultations and more enablement for more patients are found at population level for patients with psychological problems, with social problems and with physical problems. More complex problems require more time to achieve equal benefit. 4. Mean consultation length and mean enablement score correlate well with each other and can be used as summary statistics of quality. Where trends require explanation or exploration, other measures of the use of time and the level of benefit gained are more helpful; both sets of analyses can be derived from the same datasets (Chapter 3). 5. Analyses at practice level show that practices which spend more time at consultations enable patients more whatever the nature of problems presented. The rank orders of time spent at consultation and of enablement are highly correlated (Chapter 4). 6. Analyses at doctor level show that doctors who spend more time at consultations enable patients more and that those who spend less time enable patients less. The numbers of patients available for study were not sufficient to explore this association within subgroups of clinical presentations. As in previous studies, we found that doctors who take longer time are likely to be more patient centred, and those who take less time are likely to be less patient centred. Case-mix varies between doctors, but seems to be independent of whether a doctor is more or less patient centred (Chapter 5). 7. The methods developed in this study give useful insights into the definition and delivery of quality of care in general practice (Chapter 6). The measures now need to be tested in different clinical, cultural and organizational settings and results compared with those found using routinely available NHS data on prescribing and achievement of other clinical and management targets (Chapter 7).