The role of spirituality and identity formation in personal recovery from traumatic brain injury: A qualitative analysis through the personal experiences of survivors.

Traumatic brain injury (TBI) is a type of acquired brain injury (ABI) that happens when a sudden, external, physical assault damages the brain. TBI can cause long-term cognitive impairments and other lifestyle changes that may affect psychological wellbeing. Among the psychological challenges people recovering from TBI often face is the subjective loss of their pre-injury identity. Quantitative and qualitative research suggests that spirituality can play a positive role in recovery from TBI, increasing the quality of life and overall mental health. However, thus far, the research into this topic has not directly addressed the relationship between identity and spirituality after TBI. The present study sought to do this by thematically analyzing 22 public podcasts featuring interviews of people recovering from TBI telling their stories. The authors review the spiritual themes discussed in the podcasts and then propose a hypothesis about how, through a sense of connection to something self-transcendent, spirituality may enable people to test new meanings and identities, relatively free from the consequences of discrepancy in meaning and identity after TBI.

Spatial variation of the colonic microbiota in patients with ulcerative colitis and control volunteers.

OBJECTIVES: The relevance of spatial composition in the microbial changes associated with UC is unclear. We coupled luminal brush samples, mucosal biopsies and laser capture microdissection with deep sequencing of the gut microbiota to develop an integrated spatial assessment of the microbial community in controls and UC. DESIGN: A total of 98 samples were sequenced to a mean depth of 31,642 reads from nine individuals, four control volunteers undergoing routine colonoscopy and five patients undergoing surgical colectomy for medically-refractory UC. Samples were retrieved at four colorectal locations, incorporating the luminal microbiota, mucus gel layer and whole mucosal biopsies. RESULTS: Interpersonal variability accounted for approximately half of the total variance. Surprisingly, within individuals, asymmetric Eigenvector map analysis demonstrated differentiation between the luminal and mucus gel microbiota, in both controls and UC, with no differentiation between colorectal regions. At a taxonomic level, differentiation was evident between both cohorts, as well as between the luminal and mucosal compartments, with a small group of taxa uniquely discriminating the luminal and mucosal microbiota in colitis. There was no correlation between regional inflammation and a breakdown in this spatial differentiation or bacterial diversity. CONCLUSIONS: Our study demonstrates a conserved spatial structure to the colonic microbiota, differentiating the luminal and mucosal communities, within the context of marked interpersonal variability. While elements of this structure overlap between UC and control volunteers, there are differences between the two groups, both in terms of the overall taxonomic composition and how spatial structure is ascribable to distinct taxa.

Tumour microenvironment of both early- and late-stage colorectal cancer is equally immunosuppressive.

BACKGROUND: Tumour microenvironment (TME) of advanced colorectal cancer (CRC) suppresses dendritic cell (DC) maturation. Here, our aim was to determine how the microenvironment of early-stage tumours influences DCs. METHODS: Tumour-conditioned media (TCM) was generated by culturing explant tumour tissue in vitro (n=50). Monocyte-derived DCs (MDDCs) of healthy donors or cancer patients were pretreated with TCM and stimulated with lipopolysaccharide (LPS). DC maturation was assessed by flow cytometry and cytokine production measured by ELISA. RESULTS: TCM from both early- and late-staged tumours abrogated LPS-induction of IL-12p70 secretion, while increasing IL-10. The profile of inflammatory mediators in TCM was similar across stages, and all increased pSTAT3 expression by DCs.CRC patient DCs (n=31) secreted low levels of IL-12p70 and failed to upregulate expression of maturation markers in response to LPS. Furthermore, in vitro culture of autologous DCs with TCM did not change the hypo-responsiveness of patient DCs. CONCLUSION: Our data demonstrates that the TME of all stages of CRC contains inflammatory mediators capable of suppressing local DCs. MDDCs obtained from CRC patients are hyporesponsive to stimuli such as LPS. Measures to reverse the negative influence of the TME on DCs will optimise cancer vaccines in both early- and late-stage CRC.

Chronic kidney disease and diabetes in the national health service: a cross-sectional survey of the U.K. national diabetes audit.

AIMS: We investigated the prevalence of chronic kidney disease and attainment of therapeutic targets for HbA1c and blood pressure in a large U.K.-based diabetes population. METHODS: The U.K. National Diabetes Audit provided data from 1 January 2007 to 31 March 2008. Inclusion criteria were a documented urinary albumin:creatinine ratio and serum creatinine. Patients were stratified according to chronic kidney disease stage and albuminuria status. Chronic kidney disease was defined as an estimated glomerular filtration rate < 60 ml min(-1) 1.73 m(-2) , albuminuria or both. The proportions of patients achieving nationally defined glycaemic and systolic blood pressure targets were determined. RESULTS: The cohort comprised 1,423,669 patients, of whom 868,616 (61%) met inclusion criteria. Of the patients analysed, 92.2% had Type 2 diabetes. A higher proportion of people with Type 2 diabetes (42.3%) had renal dysfunction compared with those with Type 1 diabetes (32.4%). Achievement of systolic blood pressure and HbA1c targets was poor. Among people with Type 1 diabetes, 67.8% failed to achieve an HbA1c < 58 mmol/mol (7.5%). Of all people with diabetes, 37.8% failed to achieve a systolic blood pressure < 140 mmHg. Blood pressure control was poor in advanced chronic kidney disease. For example, mean (standard deviation) systolic blood pressure rose from 128.6 (15.4) mmHg among people with Type 1 diabetes and normal renal function to 141.0 (23.6) mmHg in those with chronic kidney disease stage 5 and macroalbuminuria. CONCLUSIONS: The high prevalence of chronic kidney disease and poor attainment of treatment targets highlights a large subset of the diabetes population at increased risk of cardiovascular mortality or progressive kidney disease.

Prevalence and management of chronic kidney disease in primary care patients in the UK.

BACKGROUND: This study aimed to estimate the prevalence of chronic kidney disease (CKD) in the UK in 2010 and to assess prevalence, comorbidities and comedications associated with the disease over time, following inclusion of CKD in the Quality and Outcomes Framework (QOF). METHODS: This was a retrospective, longitudinal study assessing individuals with prevalent or incident CKD (identified using estimated glomerular filtration rate readings and/or Read codes) in the General Practice Research Database (GPRD) in 2010. Individuals were assessed at two time points: in 2010 and at the date of their first classification of CKD in the GPRD. RESULTS: The prevalence of stage 3-5 CKD in 2010 was 5.9%. In patients with stage 3-5 CKD at first classification, their disease remained stable, progressed or improved by 2010 in approximately 50%, 10-15% and 25-30% of patients, respectively. Diagnoses of cardiovascular-related comorbidities (hypertension, hypercholesterolaemia, diabetes and cardiovascular disease), and treatment with antihypertensives and lipid-modifying therapy (LMT), increased with worsening disease severity. When patients were stratified by diagnosis date, the proportion of patients with stage 3-5 CKD and cardiovascular-related comorbidities decreased with time, and the relative use of LMT and antihypertensives among patients with hypercholesterolaemia and hypertension increased with time. CONCLUSIONS: Chronic kidney disease is generally stable or progressive, although more patients improve disease stage than previously assumed. Data suggest that the introduction of CKD into the QOF has increased awareness of CKD among physicians in the UK, allowing for earlier intervention and better control of CKD progression.

Management of colorectal cancer in patients with inflammatory bowel disease.

BACKGROUND: This study evaluated the clinicopathological features and survival rates of patients with inflammatory bowel disease who developed colorectal cancer (CRC). METHODS: A retrospective review was performed on a prospectively maintained institutional database (1981-2011) to identify patients with inflammatory bowel disease who developed CRC. Clinicopathological parameters, management and outcomes were analysed. RESULTS: A total of 2,843 patients with inflammatory bowel disease were identified. One thousand six hundred and forty-two had ulcerative colitis (UC) and 1,201 had Crohn's disease (CD). Following exclusion criteria, there were 29 patients with biopsy-proven colorectal carcinoma, 22 of whom had UC and 7 had CD. Twenty-six patients had a preoperative diagnosis of malignancy/dysplasia; 16 of these were diagnosed at surveillance endoscopy. Nodal/distant metastasis was identified at presentation in 47 and 71 % of the UC and CD group, respectively. Operative morbidity for UC and CD was 33 and 17 %, respectively. Despite the less favourable operative outcomes following surgery management of UC-related CRC, overall 5-year survival was significantly better in the UC group compared to the CD group (41 vs. 29 %; p = 0.04) reflecting the difference in stage at presentation between the two groups. CONCLUSIONS: Patients who undergo surgery for UC-related CRC have less favourable short-term outcomes but present at a less advanced stage and have a more favourable long-term prognosis than similar patients with CRC and CD.

Hereditary mixed polyposis syndrome due to a BMPR1A mutation.

The conditions Juvenile Polyposis Syndrome (JPS) and Hereditary Mixed Polyposis Syndrome (HMPS) are associated with an increased risk of colorectal carcinoma. The genetic mechanisms which explain these conditions have until recently been poorly understood. Recent interest has focused on the transforming growth factor (TGF)-beta signalling pathway and, in particular, on mutations in the SMAD4 gene. However, not all cases of JPS and HMPS have mutations in SMAD4 and focus has now shifted to other components of the TGF-beta pathway to clarify the genetic mechanisms involved in these conditions. In this report, we describe the significance of a bone morphogenetic protein receptor type 1A gene mutation in an Irish family.

Nuclear oxidative damage correlates with poor survival in colorectal cancer.

Oxidative DNA damage results from DNA adducts such as 8-oxo-7, 8 dihydro-2'-deoxyguanosine (8-oxo-dG), which is a pro-mutagenic lesion. No known association between 8-oxo-dG, disease progression and survival exists in colorectal cancer (CRC). We examined levels of 8-oxo-dG in sporadic CRC to determine its relationship with pathological stage and outcome. A total of 143 CRC patients and 105 non-cancer patients were studied. Nuclear and cytoplasmic 8-oxo-dG was assessed using immunohistochemistry. Double immunofluorescence using 8-oxo-dG and manganese superoxide dismutase (MnSOD) antibodies localised cytoplasmic 8-oxo-dG. Apoptosis was detected using TUNEL. Nuclear staining levels were similar in tumour tissue and matched normal mucosa in both epithelial (P=0.22) and stromal (P=0.85) cells. Epithelial cytoplasmic staining was greater in tumour tissue (P<0.001). Double immunofluorescence localised cytoplasmic 8-oxo-dG to mitochondria. Epithelial and stromal nuclear 8-oxo-dG decreased with local disease spread, but highest levels were found in distant disease (P<0.01). Survival was related to epithelial nuclear and stromal staining in normal mucosa (P<0.001) and tumour (P<0.01) but was unrelated to cytoplasmic staining. Normal control cells in tissue from cancer patients with high levels of 8-oxo-dG failed to undergo cell death. 8-oxo-dG may be an important biomarker of disease risk, progression and survival for CRC patients.

Bradykinin regulates human colonic ion transport in vitro.

BACKGROUND AND PURPOSE: Kinins are acknowledged as important regulators of intestinal function during inflammation; however, their effects on human intestinal ion transport have not been reported. Here, we used muscle-stripped human colonic tissue and cultured T(84)-cell monolayers to study bradykinin (BK) actions on human intestinal ion transport. EXPERIMENTAL APPROACH: Ion transport was measured as changes in short-circuit current (I(sc)) across colonic epithelia mounted in Ussing chambers. KEY RESULTS: In intact tissue, there was a distinct polarity to BK-elicited I(sc) responses. Whereas basolateral BK stimulated sustained responses (EC(50)=0.5+/-0.1 microM), those to apical BK were more rapid and transient (EC(50)=4.1+/-1.2 nM). In T(84) cells, responses to both apical and basolateral BK were similar to those seen upon apical addition to intact tissues. Cross-desensitization between apical and basolateral domains was not observed. BK-induced responses were largely due to Cl(-) secretion as shown by their sensitivity to bumetanide and removal of Cl(-) from the bathing solution. Studies using selective agonists and antagonists indicate responses to BK are mediated by B(2) receptors. Finally, responses to basolateral BK in intact tissues were inhibited by tetrodotoxin (1 microM), atropine (1 microM), capsaicin (100 microM) and piroxicam (10 microM). BK-stimulated prostaglandin (PG)E(2) release from colonic tissue. CONCLUSIONS: BK stimulates human colonic Cl(-) secretion by activation of apical and basolateral B(2) receptors. Responses to apical BK reflect a direct action on epithelial cells, whereas those to basolateral BK are amplified by stimulation of enteric nerves and PG synthesis.

The high prevalence of unrecognized anaemia in patients with diabetes and chronic kidney disease: a population-based study.

BACKGROUND: Anaemia occurs early in the course of diabetes-related chronic kidney disease (CKD). There is little evidence about the prevalence of anaemia in people with diabetes. The aim of this study was to assess the prevalence of anaemia, by stage of CKD, in the general diabetic population. METHODS: Haemoglobin (Hb) was measured on all glycated haemoglobin (HbA1c) samples and the most recent (< 4 months) estimated glomerular filtration rate (eGFR) was obtained. Anaemia (at treatment level) was defined as Hb < 110 g/l or the use of erythropoetic stimulating agents (ESA). RESULTS: Twelve per cent (10-14%) of people had Hb < 110 g/l. The prevalence of anaemia increased progressively with worsening CKD. People with CKD stage 3 accounted for the largest number of people with anaemia; 18% (95% CI 13-24%) had Hb < 110 g/l. Those with eGFR < 60 ml/min/1.73 m2 and not on ESA or dialysis were four (2-7) times more likely than patients with better renal function to have Hb < 110 g/l. The relation between Hb and eGFR became approximately linear below an eGFR of 83 ml/min/1.73 m2, where, for every 1 ml/min/1.73 m2 fall in eGFR, there was a 0.4 (0.3-0.5) g/l fall in haemoglobin. CONCLUSIONS: This study demonstrates that anaemia, at levels where treatment is indicated, occurs commonly in people with diabetes and CKD stage 3 or worse. The screening for anaemia in current diabetes management should be extended.

Mesangial cell autoantigens in immunoglobulin A nephropathy and Henoch-Schönlein purpura.

The autoantigen(s) that we have previously described in human glomeruli, recognized in IgA nephropathy, has (have) been identified as mesangial cell in origin. Cultured mesangial cells expressed 48- and 55-kD components binding IgG isotype autoantibodies (IgG-MESCA) present in sera of patients with both IgA nephropathy and Henoch-Schönlein purpura (HSP). IgG-MESCA were not detected in sera of normals, or patients with other autoimmune-mediated glomerulonephritides: anti-glomerular basement membrane disease, Wegener's granulomatosis, or in IgM-mesangial proliferative disease. Binding specificity was proven by F(ab')2 studies in enzyme-linked immunosorbent assay (ELISA) and Western blotting, and there was no significant affinity of IgA or IgM immunoglobulins. Fluorescein isothiocyanate-conjugated IgG from ELISA-positive sera localized to the mesangium and peripheral capillary loops of glomeruli, supporting the belief that the antigen is expressed in normal human renal tissue. However, only about one third of mesangial cells in culture showed affinity for IgG from ELISA-positive sera, suggesting variable expression of the antigen(s) in vitro. The only autoantigen(s) present in glomeruli, and extractable from whole normal glomeruli by the techniques employed, localized on the mesangial cell. In both IgA nephropathy and HSP, autoimmunity was intermittently present, with fluctuating levels of IgG-MESCA detectable in sera. There were positive correlations with the degree of glomerular injury assessed by erythrocyturia and proteinuria in IgA nephropathy, but significance was reached with only the degree of hematuria in HSP. These findings suggest a contributing role in the pathogenesis of the mesangial proliferative lesions and demonstrate autoimmunity common to both IgA nephropathy and HSP.

Infliximab therapy in Crohn's disease: a pragmatic approach?

BACKGROUND: Infliximab is recognized as an effective therapy in unresponsive luminal and fistulating Crohn's disease. The use of maintenance or 'on demand' therapy thereafter is controversial. AIM: To assess the need for maintenance infliximab therapy in a clinical setting where immunomodulatory agents are widely used and where episodic therapy is used in preference to maintenance therapy. METHODS: Ninety-three patients with Crohn's disease receiving infliximab; 72 with unresponsive luminal disease and 21 with fistulous disease. Data collected included disease site and duration, surgical and smoking history, initial response rates, duration of response maintenance and concomitant medications. RESULTS: Fifty-six of 72 (78%) patients with luminal disease and 11 of 21 (52%) with fistulous disease achieved an initial response. Ten of 67 responders required conversion to maintenance infliximab infusions, while 31 remain in remission. Patients with luminal disease and those who had not taken previous surgery had higher response rates to infliximab. Younger patients and those with small bowel disease had higher relapse rates following initial response. Three patients developed allergic reactions to infliximab and one patient died of progressive pulmonary disease 6 weeks after their first infusion. CONCLUSIONS: Many patients with Crohn's disease can be maintained successfully with an episodic infliximab regimen.

Current chronic kidney disease practice patterns in the UK: a national survey.

BACKGROUND: There is an increasing focus on improving the detection and management of patients with chronic kidney disease (CKD). Data on CKD prevalence based on population sampling are now available, but there are few data about CKD patients attending nephrology services or how such services are organized. AIM: To survey services for CKD patients nationally. METHODS: A pre-piloted questionnaire was sent to all 72 renal units in the UK, referring to the situation in June 2004. RESULTS: Seventy units (97%) responded. The median ratio of prevalent CKD patients/prevalent renal replacement therapy (RRT) patients in the 25 units with data was 3.7 (IQR 2.7-5.7) and the median ratio of CKD stage 4 and 5 patients/prevalent RRT patients was 0.6 (IQR 0.4-1.1). This gives an estimated 140 000 CKD patients under the care of UK nephrologists, with 23 000 at CKD stage 4 or 5 (excluding those on RRT). Very few units had a full complement of the recommended multi-skilled renal team. Counsellors and psychologist were the most common perceived shortages. Of 70 responding units, 50 (74%) were using low clearance clinics for management of advanced CKD patients. Elective dialysis access services often had long delays, with median waiting time for vascular access ranging between 1 and 36 weeks, and for Tenchkoff catheter, between 0 and 12 weeks. DISCUSSION: CKD patients are a significant workload for UK nephrologists. Current provision of service is variable, and services need to be re-designed to cope with the expected future increase of referral of CKD patients.

Prevalence of hypogonadism in male patients with renal failure.

BACKGROUND: Hypogonadism in men may be secondary to renal failure and is well recognised in patients with end-stage renal disease. It is thought to contribute to the sexual dysfunction and osteoporosis experienced by these patients. However, the association between hypogonadism and lesser degrees of renal dysfunction is not well characterised. METHODS: The gonadal status of 214 male patients (mean age 56 (SD 18) years) attending a renal centre was studied; 62 of them were receiving haemodialysis and 22 continuous ambulatory peritoneal dialysis for end-stage renal disease, whereas 34 patients had functioning renal transplants and 96 patients were in the low-clearance phase. Non-fasting plasma was analysed for testosterone, follicle-stimulating hormone, luteinising hormone, sex hormone-binding globulin, parathyroid hormone and haemoglobin. Creatinine clearance was estimated in patients not on dialysis, and Kt/V and urea reduction ratio were assessed in patients on dialysis. Testosterone concentrations were classified as normal (>14 nmol/l), low-normal (10-14 nmol/l) or low (<10 nmol/l). RESULTS: 56 (26.2%) patients had significantly low testosterone levels and another 65 (30.3%) had low-normal levels. No significant changes were seen in sex hormone-binding globulin or gonadotrophin levels. Gonadal status was not correlated with haemoglobin level, parathyroid hormone level, creatinine clearance, or dialysis duration or adequacy. CONCLUSION: Over half of patients with renal failure, even in the pre-dialysis phase, have low or low-normal levels of testosterone, which may be a potentially reversible risk factor for osteoporosis and sexual dysfunction. These patients may be candidates for testosterone-replacement therapy, which has been shown to improve bone mineral-density and libido in men with low and low-normal testosterone levels.

Incidence, care quality and outcomes of patients with acute kidney injury in admitted hospital care.

BACKGROUND/INTRODUCTION: Acute kidney injury (AKI) is common in acute hospital admission and associated with worse patient outcomes. AIM: To measure incidence, care quality and outcome of AKI in admitted hospital care. DESIGN: Forty-six of 168 acute NHS healthcare trusts in UK caring for 2 million acute hospital admissions per annum collected information on adults identified with AKI stage 3 (3-fold rise in serum creatinine or creatinine >354 µmol/l) through routine biochemical testing over a 5-month period in 2012. METHODS: Information was collected on patient and care characteristics. Primary outcomes were survival and recovery of kidney function at 1 month. RESULTS: A total of 15 647 patients were identified with biochemical AKI stage 3. Case note reviews were available for 7726 patients. In 80%, biochemical AKI stage 3 was confirmed clinically. Among this group, median age was 75 years, median length of stay was 12 days and the overall mortality within 1 month was 38%. Significant factors in a multivariable model predicting survival included age and some causes of AKI. Dipstick urinalysis, medication review, discussion with a nephrologist and acceptance for transfer to a renal unit were also associated with higher survival, but not early review by a senior doctor, acceptance for transfer to critical care or requirement for renal replacement therapy. Eighteen percent of people did not have their kidney function checked 1 month after the episode had resolved. DISCUSSION/CONCLUSIONS: This large study of in-hospital AKI supports the efficacy of biochemical detection of AKI in common usage. AKI mortality remains substantial, length of stay comparable with single-centre studies, and much of the variation is poorly explained (model Cox and Snell R2 = 0.131) from current predictors.

Microsatellite instability is associated with reduced disease specific survival in stage III colon cancer.

BACKGROUND: Up to 15% of colorectal cancers exhibit microsatellite instability (MSI), where errors in replication go unchecked due to defects in the mismatch repair system. This study aimed to determine survival in a large single-centre series of 1250 consecutive colorectal cancers subjected to universal MSI testing. METHODS: Clinical and pathological features of patients with colorectal cancer identified on prospectively maintained colorectal and pathology databases at St. Vincent's University Hospital from 2004 to May 2012 were examined. Mismatch repair (MMR) status was determined by immunohistochemistry. Kaplan-Meier curves, the log-rank test and Cox regression were used to associate survival with clinical and pathological characteristics. RESULTS: Of the 1250 colorectal cancers in the study period, 11% exhibited MSI (n = 138). Patients with MSI tumours had significantly lower rates of lymph node and distant metastases (MSI N+ rate: 24.8% compared with MSS N+ rate: 46.2%, p < 0.001). For Stage I and II disease MSI was associated with improved disease free survival (DSS) compared with MSS colon cancer. However, patients with Stage III MSI colon cancers had a worse DSS than those with MSS tumours. Stage III MSI tumours exhibited higher rates of lymphovascular invasion and perineural invasion than Stage I/II MSI tumours. CONCLUSION: MSI is associated with a reduced risk of nodal and distant metastases, with an improved DSS in Stage I/II colon cancer. However, when MSI tumours progress to Stage III these patients had worse outcomes and pathological features. New strategies for this cohort of patients may be required to improve outcomes.

Regional differences in the provision of adult renal dialysis services in the UK.

BACKGROUND: Provision of renal dialysis varies between UK regions. AIM: To analyse these differences in provision and investigate their causes. DESIGN: Questionnaire-based survey. METHODS: A questionnaire was posted to all renal provider units and renal commissioning groups in the UK. Questions covered issues such as dialysis modalities and patient choice. Data were collected by telephone interview (or post in some cases) and analysed using SPSS. RESULTS: All renal provider units in the UK responded. A full range of modalities was provided by the majority of units. Clear variations in the level and quality of dialysis provision were seen between the UK regions. These included variation in choice of dialysis modality, provision of high-cost drugs, vascular access waiting times, number of support staff and availability of spare dialysis slots. DISCUSSION: The considerable variation between UK regions in the provision of adult renal dialysis services cannot be entirely explained by age or ethnic variation, and is in part due to limited bed space, dialysis machines and support staff, as well as changes in commissioning arrangements. To meet the requirements of the renal national service framework in most regions, changes to policy and funding will be required, such that the relatively new commissioning groups implement more appropriate funding structures in closer dialogue with their provider units.

Severe acute renal failure in adults: place of care, incidence and outcomes.

BACKGROUND: Department of Health guidelines recommend specialist critical care facilities for patients with severe single-organ failure such as acute renal failure (ARF). Prospective studies examining incidence, causes and outcomes of ARF outside of intensive care settings are lacking. AIM: To determine the incidence, causes, place of care and outcomes of severe single-organ ARF. DESIGN: Prospective observational study. METHODS: For 6 weeks in June-July 2003, renal physicians were contacted daily, and ICUs on alternate days, to identify cases of severe single-organ ARF in the Greater Manchester area. All patients with serum creatinine >or=500 micromol/l and not requiring other organ support were included. Patients with end-stage renal disease were excluded. Survivors were followed up at 90 days and 1 year from admission. Two independent consultant nephrologists assessed each case using anonymized summaries. RESULTS: Eighty-five patients had multi-organ ARF and 28 had severe single-organ ARF (380 and 125 pmp/year, respectively). Of those with single-organ ARF, 10 (36%) had known pre-existing chronic kidney disease. Renal replacement therapy (RRT) was required in 15 (54%). Total bed occupancy on ICUs relating to single-organ ARF was 59 days (range per patient 1-21). At 90 days, 18 (64%) were alive, and 17 (94%) had independent renal function. At 1 year, 4/18 had died, none receiving RRT at the time of death. Survivors all had independent renal function. In 13 (46%) cases there was an unacceptable delay in patient transfer and in 7 (25%), delays in assessment or commencement of RRT may have adversely affected patient outcome. DISCUSSION: The incidence of ARF treated with RRT is rising. Delays in transfer to renal services may result in inappropriate ICU bed use, and may adversely affect patient outcomes. There are serious problems regarding the appropriate use of expensive and limited medical resources in the critical care area, and in providing safe and effective treatment of patients with ARF.

Urokinase-type plasminogen activator in colorectal cancer: relationship with clinicopathological features and patient outcome.

Urokinase-type plasminogen activator (u-PA) is a serine protease that has been implicated in cancer invasion and metastasis. We quantitated u-PA levels in normal colorectal mucosa, adenomatous polyps, and colorectal cancers and correlated these levels with clinicopathological features and patient survival. Detergent extracts were prepared from 133 colorectal cancers, 133 corresponding colorectal mucosal samples, and 15 synchronous adenomatous polyps. u-PA levels were determined using an ELISA, and a cancer:normal u-PA ratio was calculated for each case. u-PA levels were higher in cancers than in normal tissues, whereas adenomas had intermediate levels (P < 0.0001). u-PA levels were unrelated to clinical or pathological features. Survival was decreased in patients with a high cancer:normal u-PA ratio (P = 0.007). Multivariate survival analysis of patients undergoing curative surgery confirmed that the u-PA cancer:normal ratio was related to outcome (relative risk, 2.67; P = 0.02) and was independent of tumor stage (relative risk, 2.26; P = 0.03). Our study suggests that a high ratio of cancer to normal mucosal u-PA indicates an increased risk of colorectal cancer progression. Measurement of u-PA may provide useful prognostic information in patients undergoing curative surgery for colorectal cancer. The aggressive behavior of colorectal cancers with a high u-PA ratio suggests that the protease might be a suitable target for the development of therapeutic agents to prevent invasion and metastasis.

Peritonitis induces the synthesis of 1 alpha,25-dihydroxyvitamin D3 in macrophages from CAPD patients.

Metabolism of 25-[3H]hydroxyvitamin D3 was studied in peritoneal macrophages from renal failure patients on continuous ambulatory peritoneal dialysis (CAPD). Cells from 5 out of 8 patients with a history of peritonitis produced significant amounts of a metabolite chromatographically identical to 1 alpha,25(OH)2D3; but none was produced by cells from non-infected patients. The evidence strongly suggests that peritoneal macrophages stimulated by infection can metabolise 25OHD3 to the active vitamin D3 metabolite, 1 alpha,25(OH)2D3, when maintained in short-term primary culture.