Hugh Cairns

The Pan-Thames EPS study: treatment and outcomes of encapsulating peritoneal sclerosis

BACKGROUNDnEncapsulating peritoneal sclerosis (EPS) is a disease process that can occur as a complication of peritoneal dialysis (PD). The aim of this study was to make a general assessment of the clinical features, diagnosis, management and outcome of PD-related EPS cases from London and South-East England.nnnMETHODSnQuestionnaires were sent to 11 PD units in March 2007; cases were identified retrospectively. Outcome data on surviving patients were collected in March 2008.nnnRESULTSnA total of 111 patients were identified; the mean time on PD was 82 months (range 8-247). Mortality increased with length of time on PD, being 42% at <3 years (n = 12), 32% at 3-4 years (n = 19), 61% at 5-6 years (n = 31), 54% at 7-8 years (n = 24), 75% at 9-10 years (n = 8) and 59% at >10 years (n = 17). Twelve patients had no previous peritonitis episodes, 28 had one previous episode, 30 had two previous episodes and 33 had three or more previous episodes. Of the patients with PD details available, 41/63 were high (>0.81) transporters and 44/71 had ultrafiltration <1 l/24 h, but 7/63 were low average transporters (0.5-<0.65) and 27/71 had ultrafiltration >1 l/24 h and a few had significant residual renal function. Sixty-five (59%) patients had their PD discontinued prior to diagnosis (51 HD; 14 transplanted). CT scans were performed on 91 patients and laparotomy on 47 patients. Drug treatment consisted of tamoxifen, immunosuppression or both. The median survival was 15 months in patients treated with tamoxifen (n = 17), 12 months in patients treated with immunosuppression (n = 24) and 21 months in patients who received both (n = 13), against 13 months (n = 46) in patients who received no specific treatment. Adhesionolysis was performed in 5 patients, and 39 patients were given parenteral nutrition. The overall mortality was 53% with a median survival of 14 months and a median time to death of 7 months. Conclusion. This is one of the largest cohorts of patients with EPS in the literature. Long-term survival occurred in over 50%, regardless of the various treatments strategies undertaken by the centres.

Head Injuries in Motor-cyclists. The Importance of the Crash Helmet

During the first twenty-one months of war the number of motor-cyclists and pillion passengers killed on the road was 2,279-21 % more than during the corresponding months of peacetime (1,884 killed between September, 1937, and May, 1939). The frequency of head injuries was high (Table I), and in a number of cases the fatal outcome might have been avoided if adequate protection for the head had been worn. But, as will be observed, the issue is not clear-cut, since multiple injuries other than head injuries undoubtedly contributed to death, though to what extent cannot be defined. The second section of this paper deals with such material as it has been possible to collect relating to non-fatal head injuries to motor-cyclists; the third briefly indicates some of the causes of accidents, and offers suggestions for prevention and for protection to the heads of riders by the general use of crash helmets of a type described. In conclusion, 7 cases, seen by me, are reported of non-fatal injuries to riders wearing crash helmets, and evidence is adduced to show that in most of them graver injuries would have been sustained without such protection.

Head Injuries in Motor-cyclists: with Special Reference to Crash Helmets

In an earlier paper (Cairns, 1941) attention was called to the use of crash helmets to alleviate the head injuries of motor-cyclists, and 7 cases were reported. We now have records of 106 accidents in which we have been able to examine the crash helmet and, usually, the patient. This material provides further information about head injuries in motor-cyclists, and also enables us to compare the relative values of different types of helmet.

Effect of Exercise Training on Estimated GFR, Vascular Health, and Cardiorespiratory Fitness in Patients With CKD: A Pilot Randomized Controlled Trial

BACKGROUNDnExercise capacity, which is predictive of all-cause mortality and cardiovascular disease risk, is reduced significantly in patients with non-dialysis-dependent chronic kidney disease. This pilot study examined the effect of moderate-intensity exercise training on kidney function and indexes of cardiovascular risk in patients with progressive chronic kidney disease stages 3 toxa04.nnnSTUDY DESIGNnSingle-blind, randomized, controlled, parallel trial.nnnSETTING & PARTICIPANTSn20 patients (aged 18-80 years; 17 men) randomly assigned to rehabilitation (n=10) or usual care (n=10). Participants were included if they were 18 years or older and had evidence of rate of decline in creatinine-based estimated glomerular filtration rate (eGFRcr)≥2.9mL/min/1.73m(2) per year for 12 months preintervention. Patients were excluded if they had unstable medical conditions or had recently started regular exercise.nnnINTERVENTIONnThe rehabilitation group received resistance and aerobic training (3 days per week) for a 12-month period. The usual care group received standard care.nnnOUTCOMESnKidney function assessed by comparing mean rate of change in eGFRcr (mL/min/1.73m(2) per year) from a 12-month preintervention period against the 12-month intervention period. Pulse wave velocity (PWV), peak oxygen uptake (Vo2peak), and waist circumference assessed at 0, 6, and 12 months.nnnMEASUREMENTSneGFR assessed using creatinine, cystatin C (eGFRcys), and a combination of both values (eGFRcr-cys).nnnRESULTSn18 participants (rehabilitation, 8; usual care, 10) completed the study. A significant mean difference in rate of change in eGFRcr (+7.8±3.0 [95% CI, 1.1-13.5] mL/min/1.73m(2) per year; P=0.02) was observed between the rehabilitation and usual care groups, with the rehabilitation group demonstrating a slower decline. No significant between-group mean differences existed in absolute eGFRcr, eGFRcr-cys, or eGFRcys at 12 months of study intervention. Significant between-group mean differences existed in PWV (-2.30 [95% CI,xa0-3.02 toxa0-1.59] m/s), waist circumference (-7.1±12.8 [95% CI,xa0-12.4 toxa0-3.2] cm), and Vo2peak (5.7 [95% CI, 1.34-10.10] mL/kg/min). Change in eGFRcr was correlated inversely with PWV (r=-0.5; P=0.04) at 12 months.nnnLIMITATIONSnSmall sample size, inconsistency between primary and secondary measures of kidney function.nnnCONCLUSIONSnThe effect of a 1-year exercise intervention on progression of kidney disease is inconclusive. A larger study with longer follow-up may be necessary.

ENDOTHELIN INDUCES AN INCREASE IN RENAL VASCULAR-RESISTANCE AND A FALL IN GLOMERULAR-FILTRATION RATE IN THE RABBIT ISOLATED PERFUSED KIDNEY

1 The effects of endothelin infusion on renal vascular resistance (RVR), glomerular filtration rate (GFR) and the interaction with locally generated endothelium‐derived relaxant factor (EDRF) were studied in the rabbit isolated perfused kidney (IPK). For comparison the effects of infusions of angiotensin II (AII) and noradrenaline (NA) were also assessed. 2 Each kidney was perfused at a constant rate of 10 ml min−1 and alterations in RVR determined by measuring changes in perfusion pressure. GFR was determined by the clearance of [51Cr]‐EDTA, using timed urine collections. 3 Endothelin (10−11‐10−9 M) produced a dose‐related increase in RVR. Endothelin was approximately 30 times more potent in molar terms than AII and 500 times more than NA at inducing a 50 mmHg increase in perfusion pressure. 4 Endothelin appeared to be a weak inducer of EDRF release in the IPK as EDRF inhibitors methylene blue (10 μm) or haemoglobin (10 μm) only slightly augmented the increase in RVR at a given concentration of endothelin. In contrast the effect of NA on RVR was significantly increased by methylene blue (10 μm) whereas that induced by AII was not affected. 5 Endothelin infusion produced a significant, dose‐dependent decrease in GFR of the IPK, contrasting with an increase in GFR during AII infusion and a minimal effect of NA on GFR. This supports evidence that AII is predominantly a constrictor of efferent glomerular arterioles and that NA constricts both afferent and efferent glomerular vessels. We suggest that the vasoconstrictive effect of endothelin in the kidney is predominantly preglomerular, which explains its effect on GFR.

Fractures of the Sphenoidal Sinus with Cerebrospinal Rhinorrhoea

It isnow generally accepted that cerebrospinal fluid (C.S.F.) rhinorrhoea following a head injury indicates a dural tear in relation to a fracture involving the paranasal sinuses, and that a fascial repair of the torn dura is required as an insurance against intracranial infection in the future. Most of the fractures involve the frontal or ethmoid sinuses.* In this paper we consider only the relatively uncommon group in which the rhinorrhoea was due to fracture of the sphenoidal sinus. Such fractures are not always detected by radiological examination, and a full exploration of this region involves special problems of exposure and accessibility. it seems that there are certain clinical characteristics which may lead to their detection pre-operatively.

Cyclosporin therapy in vivo attenuates the response to vasodilators in the isolated perfused kidney of the rabbit

1 The endothelium releases a number of vasoactive compounds, including the vasodilator prostaglandins, prostacyclin (PGI2) and prostaglandin E2 (PGE2) and endothelium‐derived relaxing factor (EDRF), which play an important role in the regulation of vascular tone in the microcirculation. Nephrotoxicity is the major complication of cyclosporin (CS) therapy and is related to an increase in intrarenal vascular tone. Endothelial cell generation of PGI2 is inhibited by CS although this cannot fully explain the changes in vascular tone observed. We have investigated the possibility that EDRF‐dependent vasodilatation is also affected by CS therapy in vivo. 2 CS nephrotoxicity was induced in rabbits with CS (15 mg kg−1 per day s.c. for 20 days (n = 6)); 6 rabbits were given CS vehicle (Veh) and 9 animals were studied without any treatment. Creatinine clearance fell significantly during treatment in the CS‐treated rabbits (11.78 ± 1.5 ml min−1, mean ± s.e.mean, to 7.79 ± 1.2 after 20 days treatment) but did not change in the vehicle‐treated animals. 3 The responses to the endothelium‐dependent (acetylcholine (ACh)) and endothelium‐independent (nitroprusside (NP) and PGI2) vasodilators were assessed in indomethacin‐treated isolated perfused kidneys (IPKs) from untreated, CS‐ and Veh‐treated animals. Vascular tone was induced with a constant infusion of noradrenaline 150 nM and the perfusion rate adjusted to produce a perfusion pressure of 90 mmHg. Perfusate flow rate (22.3 ± 4.6 vs 20.4 ± 3.1 ml min−1) and glomerular filtration rate (2.04 ± 0.37 vs 1.88 ± 0.16 nl min−1) did not differ between IPKs from CS‐ and Veh‐treated animals. 4 The vasodilator response to ACh was reduced in the kidneys from CS‐treated animals compared with those from untreated and Veh‐treated animals (mean reduction 35.3 ± 2.3% compared with Veh) as were the responses to both NP (42.8 ± 3.6%) and PGI2 (27.7 ± 7.4%). 5 This suggests that CS nephrotoxicity is not mediated via an effect on endothelium‐dependent responses and that it is more likely that CS has a direct effect on vascular smooth muscle.

Renal biopsy in liver transplant recipients

BACKGROUNDnRenal impairment post-liver transplant (LT) is often attributed to calcineurin inhibitors (CNIs). A renal biopsy can be a useful tool but may be complicated in LT recipients. We aimed to determine the clinical scenarios that prompted a decision to perform a renal biopsy in this patient population, to assess histological findings and evaluate patient management and survival and renal outcome.nnnMETHODSnInformation on clinical variables and renal histology was extracted from single-centre prospectively compiled databases from 1996 onwards.nnnRESULTSnOver 2100 adults received an LT in the time period studied, and 54 of these (35 males and 19 females) were referred for renal review. Of these, 43% underwent a renal biopsy. They had a higher creatinine (P = 0.02), a greater deterioration in creatinine over the year prior to review and were more likely to be nephrotic (both P < 0.01). Histological findings included hypertensive changes (44%), CNI nephrotoxicity (48%), IgA nephropathy (9%), membranoproliferative glomerulonephritis (17%), acute tubular necrosis (4%), crescentic glomerulonephritis (4%) and diabetic nephropathy (9%). Major bleeding complications occurred in 17%. Treatment changed in the majority but, it was not significantly different in the two groups. Although initial renal function was worse in the biopsied group, final patient and renal survival did not differ between the two groups.nnnCONCLUSIONnA renal biopsy is a valuable tool in those with renal insufficiency and/or proteinuria and haematuria but the benefits must be weighed against the relatively high complication rate in LT recipients.

Outcomes of the European Working Time Directive

From 56 to 48 hours is a step too far

Failure of cyclosporine-treated renal allograft recipients to increase glomerular filtration rate following an amino acid infusion

Renal allograft recipients treated with cyclosporine (CsA) have increased renal vascular resistance that falls when CsA is stopped. With the aim of identifying whether CsA-treated patients with excellent renal function also have an alteration in renal vascular tone and to investigate which vessels are affected, we have studied the response of GFR and effective renal plasma flow (ERPF) to an infusion of an amino acid solution in a group of 9 CsA-treated renal transplant recipients with a normal plasma creatinine concentration (104±3.8 μmol/L [mean ± SEM]). A similar group of 9 azathi-oprine-treated patients with good renal function (91 ± 3.6 /μmol/L) were used as controls. The azathioprine group had significant increases in both GFR (22%, P<0.05) and ERPF (19%, P<0.05) following a protein load, whereas there was no increase in either function in the CsA group. Amino acid infusions increase GFR and ERPF in normal kidneys—at least in part by producing afferent glomerular arteriolar dilatation. The difference we found between the two groups indicates a direct effect of cyclosporine on intrarenal vascular tone, even when renal function is considered to be normal.