Do personality traits assessed on medical school admission predict exit performance? A UK-wide longitudinal cohort study.

Traditional methods of assessing personality traits in medical school selection have been heavily criticised. To address this at the point of selection, "non-cognitive" tests were included in the UK Clinical Aptitude Test, the most widely-used aptitude test in UK medical education (UKCAT: http://www.ukcat.ac.uk/ ). We examined the predictive validity of these non-cognitive traits with performance during and on exit from medical school. We sampled all students graduating in 2013 from the 30 UKCAT consortium medical schools. Analysis included: candidate demographics, UKCAT non-cognitive scores, medical school performance data-the Educational Performance Measure (EPM) and national exit situational judgement test (SJT) outcomes. We examined the relationships between these variables and SJT and EPM scores. Multilevel modelling was used to assess the relationships adjusting for confounders. The 3343 students who had taken the UKCAT non-cognitive tests and had both EPM and SJT data were entered into the analysis. There were four types of non-cognitive test: (1) libertariancommunitarian, (2) NACE-narcissism, aloofness, confidence and empathy, (3) MEARS-self-esteem, optimism, control, self-discipline, emotional-nondefensiveness (END) and faking, (4) an abridged version of 1 and 2 combined. Multilevel regression showed that, after correcting for demographic factors, END predicted SJT and EPM decile. Aloofness and empathy in NACE were predictive of SJT score. This is the first large-scale study examining the relationship between performance on non-cognitive selection tests and medical school exit assessments. The predictive validity of these tests was limited, and the relationships revealed do not fit neatly with theoretical expectations. This study does not support their use in selection.

Does the UKCAT predict performance on exit from medical school? A national cohort study.

OBJECTIVES: Most UK medical programmes use aptitude tests during student selection, but large-scale studies of predictive validity are rare. This study assesses the UK Clinical Aptitude Test (UKCAT: http://www.ukcat.ac.uk), and 4 of its subscales, along with individual and contextual socioeconomic background factors, as predictors of performance during, and on exit from, medical school. METHODS: This was an observational study of 6294 medical students from 30 UK medical programmes who took the UKCAT from 2006 to 2008, for whom selection data from the UK Foundation Programme (UKFPO), the next stage of UK medical education training, were available in 2013. We included candidate demographics, UKCAT (cognitive domains; total scores), UKFPO Educational Performance Measure (EPM) and national exit situational judgement test (SJT). Multilevel modelling was used to assess relationships between variables, adjusting for confounders. RESULTS: The UKCAT-as a total score and in terms of the subtest scores-has significant predictive validity for performance on the UKFPO EPM and SJT. UKFPO performance was also affected positively by female gender, maturity, white ethnicity and coming from a higher social class area at the time of application to medical school An inverse pattern was seen for a contextual measure of school, with those attending fee-paying schools performing significantly more weakly on the EPM decile, the EPM total and the total UKFPO score, but not the SJT, than those attending other types of school. CONCLUSIONS: This large-scale study, the first to link 2 national databases-UKCAT and UKFPO, has shown that UKCAT is a predictor of medical school outcome. The data provide modest supportive evidence for the UKCAT's role in student selection. The conflicting relationships of socioeconomic contextual measures (area and school) with outcome adds to wider debates about the limitations of these measures, and indicates the need for further research.

A remedial intervention linked to a formative assessment is effective in terms of improving student performance in subsequent degree examinations.

BACKGROUND: Intervention may help weaker medical students improve their performance. However, the effectiveness of remedial intervention is inconclusive due to small sample sizes in previous studies. We asked: is remedial intervention linked to a formative assessment effective in terms of improving student performance in subsequent degree examinations? METHODS: This was a retrospective, observational study of anonymous databases of student assessment outcomes. Data were analysed for students due to graduate in the years 2005-2009 (n = 909). Exam performance was compared for students who received remediation versus those who did not. The main outcome measure was summative degree examination marks. RESULTS: After adjusting for cohort, gender, overseas versus home funding, previous degree and previous performance in the corresponding baseline third year summative exam, students receiving a remedial intervention (after poor performance on a formative objective structured clinical examination and written exams mid-fourth year) were significantly more likely to obtain an improved mark on end-of-fourth year summative written (p = 0.005) and OSCE (p = 0.001) exams compared to those students who did not receive remediation. CONCLUSION: A remedial intervention linked to poor assessment performance predicted improved performance in later examination. There is a need for prospective studies in order to identify the effective components of remedial interventions.

Introducing endovenous laser therapy ablation to a national health service vascular surgical unit - the Aberdeen experience.

OBJECTIVES: To report early clinical outcomes and learning experience following the introduction of endovenous laser ablation (EVLA) to an NHS vascular unit. DESIGN: Prospective observational study. RESULTS: Between February 2006 and January 2008, 631 consecutive patients underwent EVLA to 704 refluxing truncal veins - 579 GSV, 119 SSV and 6 straight segments of anterior accessory GSV. 275/631 (44%) patients had local anaesthesia (LA) plus sedation, 237 (38%) had LA only and 119 (18%) had general anaesthesia. All were treated using the 810 nm diode laser. Adjuvant procedures on-table included foam sclerotherapy 129/704 (18%), multiple stab avulsions 53/704 (8%) and 3 limbs had both. Three-month follow-up with duplex examination is complete in 635/704 limbs (90%). Complete occlusion was noted in 610 veins (96%), 14 (2.2%) were partially occluded and 11 (1.7%) showed no occlusion. 193 (30%) of the 635 limbs seen at follow-up required further treatment for residual varicosities using foam sclerotherapy. There has been one non-fatal pulmonary embolus associated with EVLA and no other complications. CONCLUSIONS: EVLA is safe and technically effective. It has a defined learning curve requiring new operator skills which can be readily acquired.

The effect of superficial venous surgery on generic health-related quality of life.

BACKGROUND: Superficial venous surgery (SVS) is associated with a significant improvement in disease-specific health related quality of life (HR-QoL) but the effect on generic HR-QoL remains uncertain. The aim of this study was to determine the effect of SVS on responses to the Short Form [SF]-36, the most widely used generic HR-QoL instrument. METHOD: Two hundred and three patients undergoing SVS completed the SF-36 pre-operatively and 24 months post-operatively. Scores for the 8 SF-36 domains [physical (PF) and social functioning (SF), role limitation due to physical (RP) and emotional (RE) problems, mental health (MH), vitality (V), pain (P), and general health perception (HP)] were calculated and normalised using UK standard data. RESULTS: Pre-operatively, patients scored significantly lower (worse) than the general UK population in PF, RP and P. Surgery was associated with a significant improvement in PF and P (45.3 vs. 42.5 and 48.9 vs. 43.8 postop vs. preop, p<0.001, WSR) at 2 years. CONCLUSION: SVS leads to a statistically and clinically significant improvement in the physical components of the SF-36. These data will allow the clinical benefits of SVS to be compared with other interventions so helping informing decisions about how venous surgery should be prioritised appropriately within the NHS.

The effect of long saphenous vein stripping on deep venous reflux.

BACKGROUND: The addition of long saphenous vein (LSV) stripping to sapheno-femoral junction (SFJ) disconnection and multiple stab avulsions (MSAs) in the course of varicose vein (VV) surgery is associated with a significant reduction in recurrence, and a significant improvement in quality of life. It is hypothesised that these benefits relate, at least in part, to a favourable effect of stripping on deep venous reflux. OBJECTIVE: To examine the effect of long saphenous vein (LSV) stripping on deep venous reflux (DVR). METHODS: This was prospective study of 62 consecutive patients (77 limbs) CEAP class 2-6, undergoing SFJ disconnection and MSAs, with and without successful stripping of the LSV to the knee. A duplex ultrasound examination was performed pre-operatively and at a median (IQR) of 24 (23-25) months post-operatively. Completely stripped limbs were defined as those in whom complete stripping of the LSV to the knee was confirmed on post-operative duplex. Reflux >/=0.5 s. was considered pathological. RESULTS: Pre-operatively, 32 (42%) limbs had deep venous reflux (DVR). Post-operative duplex at 24 months revealed that the LSV had been completely stripped in 29 (38%) limbs. In patients with pre-operative DVR, complete stripping was associated with a significant reduction in the prevalence of superficial femoral vein (SFV) (p<0.001) and popliteal vein (PV) (p=0.016), McNemar test) on post-operative duplex. By contrast, in patients without pre-operative DVR, incomplete stripping was associated the development of SFV (p=0.031) and PV (p=0.008) reflux. CONCLUSIONS: Complete LSV stripping abolishes DVR in a significant proportion of limbs, whereas failure to strip is frequently associated with the development of new DVR. These data support for routine stripping and suggest that the benefits of stripping may relate, at least in part, to a favourable impact on deep venous function.

The benefits of a curved suture needle in laparoscopic partial fundoplications in infants.

A modified Watson fundoplication technique is described using curved needles introduced through the anterior abdominal wall. This technique has clear advantages over ski needles, allows for a wider choice of sutures and helps curtail costs in laparoscopic fundoplication in the small child.

Laparoscopic decapsulation of congenital splenic cysts: a step forward in splenic preservation.

PURPOSE: The aim of this study was to evaluate the role of laparoscopic decapsulation in the management of congenital splenic cysts in children. METHODS: Patients who presented over the last decade with congenital splenic cysts and were treated with laparoscopic decapsulation were reviewed retrospectively. The authors performed 4 procedures in 3 patients aged 10, 11 (and later 13), and 13 years. In all cases there was progressive enlargement of a single cyst, which lay in the upper pole of the spleen in 3 instances and in the lower pole in the fourth. Pneumoperitoneum was induced using the Veress needle technique, and 3 or 4 ports were utilized. Cysts were aspirated initially before marsupialization with excision of around two thirds of the cyst wall. Both endoshears and the harmonic scalpel were used with good hemostatic effect. RESULTS: All patients had a good outcome with cyst resolution on long-term follow-up using serial ultrasound scanning. The first patient (in 1993) remained 3 days as an in patient postoperatively, and the others stayed overnight only. One patient had a new cyst near the first 30 months after the initial procedure. This again was dealt with laparoscopically, with patient discharge the following day. There were no complications in the short or long term. Histology in all cases confirmed a simple epithelial cyst. Median follow-up was 2 years (range, 6 months to 8 years). CONCLUSIONS: Our experience shows that laparoscopic decapsulation is an effective means of managing congenital splenic cysts and that both harmonic scalpel and endoshears are satisfactory dissecting instruments. Extensive marsupialization is probably unnecessary in these larger cysts, because long-term follow-up has shown no increased risk of recurrence after leaving a significant proportion of the cyst wall behind. This approach helps avoid major surgery in these cases.

Carotid endarterectomy in patients aged 75 and over: early results and late outcome.

BACKGROUND: The mean age of patients in the European Carotid Surgery Trial with greater than 70% stenosis was 62 years. With changing demographics older patients are increasingly being referred for carotid endarterectomy (CEA). OBJECTIVES: To assess the complications and survival (stroke-free and overall) of patients over the age of 75 undergoing CEA. METHODS: Analysis of a database, clinical records and cause of death of patients undergoing CEA in a single regional unit over a 7 year period (1/4/1993 until 1/4/2000), with follow-up to April 2002. The rates of further neurological events were obtained from the Scottish Morbidity Record 1 (SMR 1) of hospital discharges. Patients referred from outside the region were excluded. Differences between groups were assessed by the Chi-squared test, with Yates correction and log-rank tests. RESULTS: Of the 235 patients undergoing CEAs, 55 (23%) were 75 years or older. The post-operative neurological complication rate was 1.7% in the under 75's and 5.4% in the older group (p < 0.05). The 30 day mortality was 1.1% (two patients) and 1.8% (one patient) respectively. The Kaplan-Meier estimated survival for the under 75's and older were 93 and 75% at 3 years and 80 and 59% at 5 years respectively (p < 0.001). The Kaplan-Meier estimated neurological event-free 5 year survival for the under 75's and older patients were 96 and 82% respectively (p < 0.001). CONCLUSION: CEA in patients aged 75 years and over is associated with a significantly increased risk of stroke and death. CEA may not benefit elderly patients with a reduced life expectancy.

A comparison of patients who developed venous leg ulceration before and after their 50th birthday.

BACKGROUND: although chronic venous ulceration (CVU) is often viewed primarily as a disease of the elderly, recent epidemiological data suggest that a significant proportion of patients first develop CVU before middle age. Such patients may represent a distinct group in terms of aetiology, natural history, prognosis and therapeutic options. AIM: to compare patients who developed CVU before (Group 1) and after (Group 2) their 50th birthday. METHODS: one hundred and eighteen consecutive patients with "pure" CVU underwent history and examination, measurement of ankle-brachial pressure index (ABPI) and duplex ultrasound examination of the affected limb. Pure venous ulcers were defined as those of >4 weeks duration in the presence of venous reflux (>0.5) and in association with an ankle: brachial pressure index of >0.8. RESULTS: patients in Group 1 (n = 54, 46%) were more likely to be male (32/54 [59%] vs 14/64 [23%], p < 0.001 chi(2)), to have a higher median (interquartile [IQR]) body mass index (32 [27-39] vs 27 [23-34], p = 0.003, Mann-Whitney U [MWU]), to have a history of deep venous thrombosis (23/54 [43%] vs 16/64 [25%], p = 0.04 chi(2)) and of ipsilateral long bone fracture (13/54 [24%] vs 5/64 [8%], p = 0.01, chi(2)), to have previously undergone venous surgery (27/54 [50%] vs 19/64 [30%] a median (IQR) of 11.5 (6.5-19) and 10 (2-20) years earlier respectively, and to have worse disease in terms of the duration of present ulcer (12 (6-36) vs 8.5 [3-18] months, p = 0.035 MWU), the total duration of ulcer disease (216 [72-360] vs 48 [12-120] months, p < 0.001 MWU), and the number of episodes of ulceration (3 [2-7] vs 1 [1-3], p = 0.002 MWU). There was no significant difference between the two groups in the pattern and severity of venous reflux with 46/54 (85%) of Group 1 and 54/64 (84%) of Group 2 patients having surgically correctable superficial venous reflux. CONCLUSION: patients who develop CVU before their 50th birthday appear to represent a distinct group in terms of aetiology, natural history and prognosis. The importance of thrombo-embolic prophylaxis in the prevention, and the detection and correction of superficial venous reflux in the treatment, of such ulcers is re-emphasised.

Thrombophilia and chronic venous ulceration.

It is known that thrombophilia (TP) is a risk factor for deep venous thrombosis (DVT), and that DVT predisposes to chronic venous ulceration (CVU). However, the relationship between TP and CVU has not been well studied. Review of the literature reveals that the prevalence of TP in CVU patients is high--similar to the prevalence found in patients with a history of DVT. This is despite many patients with CVU having no clear history, or duplex evidence of previous DVT. TP may predispose to CVU by leading to macro- or micro-vascular thrombosis. This association raises several issues regarding the investigation, prevention and management of patients with venous disease.

The effect of long saphenous vein stripping on quality of life.

PURPOSE: Long saphenous vein (LSV) stripping in the treatment of varicose veins may reduce the recurrence of varices but may also increase morbidity rates. The effect of stripping on health-related quality of life (HRQoL) is unknown. The aim of this study was to examine the effect of LSV surgery, with and without successful stripping, on HRQoL. METHODS: This prospective study comprises 102 consecutive patients who underwent varicose vein surgery that included attempted stripping of the LSV to the knee. HRQoL was assessed before surgery and at 4 weeks, 6 months, and 2 years after surgery with the Aberdeen varicose vein severity score (AVSS; disease-specific) and the Short-Form 36 (SF-36; generic). Patients defined as stripped were those in whom complete thigh stripping to the knee was confirmed with postoperative duplex scanning at 2 years. Patients defined as incompletely stripped were those in whom any LSV remnant was found in the thigh after surgery. Deep venous reflux (DVR) was defined as reflux of 0.5 seconds or more in at least the popliteal vein. RESULTS: Sixty-six of 102 patients (65%) provided complete HRQoL data at all four time points. At baseline, there was no significant difference between patients who were stripped (n = 25) and incompletely stripped (n = 41) in terms of AVSS, SF-36, age, gender, DVR, or CEAP grade. Significantly more patients in the incompletely stripped group underwent surgery for recurrent disease (29/41, 71%, versus 8/25, 32%; P =.002, with chi(2) test). Both groups gained significant improvements in AVSS scores for as much as 2 years. After adjustment for recurrent disease, stripping conferred additional benefit in terms of AVSS at 6 months (median [interquartile range]) (9 [4 to 16] versus 15 [9 to 24]; P =.031) and 2 years (7 [2 to 10] versus 9 [5 to 15]; P =.014), which was statistically significant in patients without preoperative DVR but not significant in patients with preoperative DVR. SF-36 scores were not affected by stripping. CONCLUSION: LSV surgery leads to a significant improvement in disease-specific HRQoL for as much as 2 years. In patients without DVR, stripping to the knee confers additional benefit.

Is there a role for balloon dilatation of pelvi-ureteric obstruction in children?

PURPOSE: The aim of this study was to examine the effectiveness of balloon dilatation with double J stenting in the management of children with pelvi-ureteric junction (PUJ) obstruction. METHODS: A retrospective study of a 4-year experience of PUJ balloon dilatation in children was conducted in a single unit. Information was collected on patient demographics, clinical presentation, the procedure of balloon dilatation, renal function, and antero-posterior renal pelvis diameter both pre- and postoperatively. RESULTS: There were 10 patients with a median age of 12.5 years (range, 21 months to 15 years). Four cases presented with ipsilateral flank pain, 3 with urinary tract infection, and 3 were discovered incidentally. Retrograde dilation was performed in all cases. Dilation was considered an initial success in 8 of 10 cases, and 1 patient deteriorated after 17 months. Double J stents were placed in all cases and remained in situ for a median of 7.5 weeks (range, 7 to 8.5). Median in-hospital stay was 2 days. Median follow-up was 34 months (range, 7 to 48). Ipsilateral renal excretion times (on MAG III isotope scanning) improved markedly from a median of 84 minutes (range 13 to 200) preoperatively to 7 minutes (range, 1 to 200) at 3 months and 7 minutes (range 1 to 113) at 12 months postoperatively. Median pelvic AP diameter reduced from 30 mm (range 22 to 74) to 16 mm (range, 8 to 36) at 2 months and 10 mm (range, 4 to 41) at 7 months. There were 2 immediate failed procedures, both occurred in patients who went on to open pyeloplasty and were found to have aberrant renal vessels causing extrinsic PUJ compression. One child deteriorated between 10 and 17 months and went on to open pyeloplasty. Twenty-two patients underwent open pyeloplasty in the unit during the same time period with a 95% success rate. Median stay was longer at 5 days and median age younger at 22 months (range, 6 weeks to 13 years). CONCLUSION: Balloon dilatation is a viable option in the management of PUJ obstruction, carrying minimal morbidity in experienced hands.

In vivo exposure to bicarbonate/lactate- and bicarbonate-buffered peritoneal dialysis fluids improves ex vivo peritoneal macrophage function.

The impact on peritoneal macrophage (PMO) function of acidic lactate-buffered (Lac-PDF [PD4]; 40 mmol/L of lactate; pH 5.2) and neutral-pH, bicarbonate-buffered (TB; 38 mmol/L of bicarbonate; pH 7. 3) and bicarbonate/lactate-buffered (TBL; 25 mmol/L of bicarbonate/15 mmol/L of lactate; pH 7.3) peritoneal dialysis fluids (PDFs) was compared during a study of continuous therapy with PD4, TB, or TBL. During a run-in phase of 6 weeks when all patients (n = 15) were treated with their regular dialysis regimen with Lac-PDF, median PMO tumor necrosis factor alpha (TNFalpha) release values were 203.6, 89.9, and 115.5 pg TNFalpha/10(6) PMO in the patients subsequently randomized to the PD4, TB, and TBL treatment groups, respectively. Median stimulated TNFalpha values (serum-treated zymosan [STZ], 10 microgram/mL) were 1,894.6, 567.3, and 554.5 pg TNFalpha/10(6) PMO in the same groups, respectively. During the trial phase of 12 weeks, when the three groups of patients (n = 5 per group) were randomized to continuous treatment with PD4, TB, or TBL, median constitutive TNFalpha release values were 204.7, 131.4, and 155.4 pg TNFalpha/10(6) PMO, respectively. Stimulated TNFalpha values (STZ, 10 microgram/mL) were 1,911, 1,832, and 1,378 pg TNFalpha/10(6) PMO in the same groups, respectively. Repeated-measures analysis of variance comparing the run-in phase with the trial phase showed that PMO TNFalpha release was significantly elevated in patients treated with both TB (P = 0.040) and TBL (P = 0.014) but not in patients treated with Lac-PDF (P = 0. 795). These data suggest that patients continuously exposed to bicarbonate- and bicarbonate/lactate-buffered PDFs might have better preserved PMO function and thus improved host defense status.

Bicarbonate/lactate- and bicarbonate-buffered peritoneal dialysis fluids improve ex vivo peritoneal macrophage TNFalpha secretion.

Peritoneal macrophage (PMO) function was examined ex vivo after their in vivo exposure to either acidic, lactate-buffered solutions (PD4; 40 mM lactate, pH 5.2), bicarbonate/lactate-buffered solution (TBL; 25 mM/15 mM bicarbonate/lactate, pH 7.3), or bicarbonate-buffered solution (TB; 38 mM bicarbonate, pH 7.3), containing either 1.36 or 3.86% glucose. Initial experiments demonstrated that tumor necrosis factor-alpha (TNFalpha) release (assessed by TNF-direct immunoassay [DIA]) from PMO isolated from the peritoneal cavities of patients exposed to conventional fluid (PD4 1.36% glucose) was lowest after 30 min of intraperitoneal dwell (3591+/-1200 versus 28,946+/-9359 for 240-min dwell [pg/ml], n=5, P < 0.05). Five patients were exposed on 3 successive days to PD4, TBL, and TB for 30-min acute dwells containing 1.36% glucose in the first week and 3.86% glucose during the second. PMO TNFalpha release was assessed after ex vitro exposure to lipopolysaccharide (LPS). Exposure of PMO to TBL or TB (1.36% glucose) resulted in a significant increase in the generation of TNFalpha (pg/2 X 10(6) PMO) compared with PD4. TBL: 68,659+/-35,633, TB: 53,682+/-26,536 versus PD4 17,107+/-8996 (LPS 1.0 ng/ml, n=5 patients, P=0.043 versus PD4 for both). PMO that were recovered from PD4 and TB dwells (3.86% glucose) showed no significant difference in TNFalpha secretion (21,661+/-6934 and 23,923+/-9147, respectively). In contrast, exposure to TBL resulted in a significant increase (41,846+/-11,471) compared with PD4 (LPS 1.0 ng/ml, n=5 patients, P=0.043). These data demonstrate enhanced PMO function after in vivo exposure to bicarbonate- and bicarbonate/lactate-buffered solutions. This response was sustained in TBL alone at the highest glucose concentrations. These results suggest that the newer solutions, and particularly bicarbonate/lactate, might improve host defense status in peritoneal dialysis patients.

Staphylococcal exoproducts down-regulate cyclooxygenase 1 and 2 in peritoneal macrophages.

Peritoneal macrophages (PMOs) are important components of the host defense against microbial infection in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Incubation of human PMOs with cell-free supernatant (BFS), prepared from Staphylococcus aureus, inhibited prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) production. Slot-blot analysis of cyclooxygenase-1 (Cox-1) and Cox-2 demonstrated a decrease in both Cox-1 (29%) and, to a greater extent, Cox-2 (65%) protein expression after BFS stimulation. When competitive polymerase chain reaction (PCR) was used, the peak levels of Cox-1 and Cox-2 messenger ribonucleic acid (mRNA) in unstimulated PMOs were 0.304+/-0.13 pmol/L and 9.61+/-2.84 pmol/L (mean+/-SEM, n = 3), respectively. After exposure of samples to BFS for 30 minutes, the level of Cox-2 mRNA was reduced to 0.59+/-0.449 pmol/L (16-fold reduction, p < 0.05), and the level of Cox-1 mRNA was reduced to 0.02+/-0.002 pmol/L (15-fold reduction, p < 0.05). In contrast, these same PMOs showed an increased expression of IL-6 mRNA and increased secretion of IL-6 protein. These results indicate that prostaglandin production in PMOs is regulated by alterations in both immunoreactive Cox-1 and Cox-2. The down-regulation of Cox metabolism in these cells is primarily related to the delayed and depressed increase in the Cox-2 gene product.

Macrophages and mesothelial cells in bacterial peritonitis.

Research in recent years has examined the mechanisms underlying cellular host defence in the peritoneal cavity. These studies have established that the resident cells of the peritoneal cavity, the peritoneal macrophages (PM phi) and the mesothelial cells (HPMC) contribute to the initiation, amplification and resolution of peritoneal inflammation. Ex vivo measurements of intra-peritoneal inflammatory mediators during peritonitis has elucidated the time courses for the generation of proinflammatory, chemotactic and anti-inflammatory cytokines and have identified that their secretion occurs largely within the peritoneum. These studies provide evidence that both PM phi- and HPMC-derived mediators are directly involved in controlling inflammation. It has been widely accepted that resident PM phi form the first line of defence against peritoneal infection, a more contemporary view would suggest that the direct or indirect (via secreted pro-inflammatory cytokines) interaction between PM phi and HPMC is pivotal to the activation and subsequent amplification of the peritoneum's response to infection. Whilst the site of these interactions is unknown, considerable evidence suggests that it occurs on the surface of the mesothelium, where invading micro-organisms may colonize. In this respect Staphylococcal exoproducts can directly activate HPMC cytokine synthesis. Once the inflammatory response is initiated, recent evidence suggests, that mesothelial cells upon activation by PM phi-derived IL-1 beta and TNF-alpha, are capable of amplifying inflammation and generating signals (via the creation of a gradient of chemotactic cytokines, IL-8, MCP-1 and RANTES) for the recruitment of leukocytes into the peritoneum. This process is also facilitated via the cytokine driven up-regulation of adhesion molecule expression (ICAM-1 and VCAM-1) on HPMC. Much less is understood about the mechanisms by which inflammation is resolved, although the secretion of anti-inflammatory molecules (IL-6, IL-1ra and soluble TNF-p55/75) by receptors by PM phi and HPMC may be important in the process. The existence of a peritoneal cytokine network controlling inflammation is now well established, within this the interaction of PM phi and HPMC appears to play a pivotal role in the hosts response to peritoneal infection.

The response of human peritoneal macrophages to stimulation with bacteria isolated from episodes of continuous ambulatory peritoneal dialysis-related peritonitis.

The metabolism of arachidonic acid, by isolated peritoneal macrophages in response to stimulation with microorganisms isolated from continuous ambulatory peritoneal dialysis (CAPD) patients, is not specific to the individual strain but is determined by species. Isolates of Staphylococcus aureus (n = 7) and Staphylococcus epidermidis (n = 13) produced a significant increase in leukotriene B4 generation by peritoneal macrophages compared with unstimulated cells (P less than .001). The coincubation of peritoneal macrophages with gram-negative organisms (n = 3), however, did not result in an increase in leukotriene B4 synthesis. In contrast, all the organisms tested significantly inhibited the formation of prostaglandin E2 and thromboxane B2 but the degree of inhibition was species dependent. The above results were reproduced using bacteria-free supernatants, indicating that the interaction was dependent on a secreted bacterial product. Thus in response to certain bacterial species, the recruitment of neutrophils may be facilitated by the generation of leukotriene B4 from peritoneal macrophages. In addition, the reduction in synthesis of prostaglandin E2 may remove a regulatory effect that this metabolite has on the immune response.