Young people's views of mental health education in secondary schools: a Scottish study.

BACKGROUND: This exploratory study used mixed methods to investigate young people's preferences in the delivery of mental health education and to investigate possible age and gender differences. METHOD: Information was gathered about the delivery of mental health education in three secondary schools. Nine pupil focus groups were carried out to identify key themes which were then further developed and administered through questionnaires to a larger sample of 773 pupils. RESULTS: Gender and age differences were found in young people's preferences about who should deliver mental health education, and what, when, where and how this should be delivered. CONCLUSION: Mental health education should reflect the needs of young people. Age and gender preferences should be considered when designing these programmes.

Renal amyloidosis in intravenous drug users.

BACKGROUND: Intravenous drug abuse is associated with a wide variety of acute and chronic medical complications. The increased longevity of drug users has seen the emergence of new diseases as a result of chronic bacterial and viral infection. We recently observed an increase in the number of cases of renal amyloidosis among intravenous drug users in central London. AIM: To describe here the demographic and clinical characteristics of such patients. METHODS: Patients were identified retrospectively from computerized patient renal biopsy records at University College London and Royal Free Hospitals from 1990-2005. Clinical information was collected from patient hospital records. RESULTS: We identified 20 cases of AA amyloidosis; 65% occurred between January 2000 and September 2005. All were proteinuric (mean 7.3 g/l, range 0.5-14.8 g/l) and 13 required dialysis within 1 month of diagnosis. Of the remaining seven, four developed end-stage renal failure after mean follow-up of 16 months (range 6-30). Nine died, with median survival of 19 months (range 1-62); all deaths were due to sepsis. DISCUSSION: Secondary AA amyloidosis is a serious complication of chronic soft tissue infection in intravenous drug users in central London. Affected individuals invariably presented with nephrotic range proteinuria and advanced renal failure. Treatment options are limited and the outcome for such patients on renal replacement was poor. Cross-disciplinary strategies are needed to prevent this serious complication of long-term intravenous drug abuse.

Acute administration of L-arginine does not improve arterial endothelial function in chronic renal failure.

BACKGROUND: Reduced activity of the nitric oxide (NO) pathway has been implicated in the endothelial dysfunction that occurs in patients with renal failure. NO is generated from L-arginine by NO synthase, and certain uremic toxins including asymmetrical dimethyl-L-arginine (ADMA), inhibit NO synthase and might contribute to endothelial dysfunction. We hypothesized that exogenous L-arginine might improve endothelial function in patients with renal failure by overcoming the effects of uremic toxins. METHODS: Endothelial function of the forearm resistance vasculature was assessed using plethysmography to measure the dilator response to intra-arterial acetylcholine (25 to 100 nmol/min). Endothelial function of radial and brachial arteries was assessed using vascular ultrasound to measure the dilator response to flow during reactive hyperemia (flow-mediated dilation; FMD). Studies were performed before and after administration of L-arginine by intra-arterial infusion (50 micromol/min) in 8 pre-dialysis patients or by intravenous infusion (10 g) in 18 hemodialysis patients. RESULTS: Local L-arginine did not improve the dilator response of forearm resistance vessels (AUC 23.1 +/- 6.4 pre, 23.1 +/- 5.1 post; P = 0.9) or FMD of the radial artery (6.5 +/- 1.2% pre, 6.3 +/- 0.8% post; P = 0.8). Systemic L-arginine did not improve FMD of the brachial artery (4.1 +/- 1.1% pre, 3.0 +/- 1.1% post; P = 0.07). These data demonstrate that acute local or systemic administration of L-arginine did not improve endothelial function in resistance or conduit arteries of patients with chronic renal failure. CONCLUSION: The results suggest that competitive inhibition of nitric oxide synthase (NOS) by circulating inhibitors is not the principal explanation for impaired endothelial dilator function in chronic renal failure.

Low dose dopamine infusion reduces renal tubular injury following cardiopulmonary bypass surgery.

BACKGROUND: The use of dopamine to protect the kidneys against hypoperfusion injury remains controversial with little clinical evidence of benefit and increasing concerns regarding safety. In this double-blind, prospective, randomised study, we investigated the effect of dopamine infusion (2.5 microg/kg/min) on glomerular filtration rate (GFR) and tubular injury in patients undergoing routine cardiopulmonary bypass (CPB). METHODS: Forty eight patients were randomly assigned to receive intravenous dopamine or saline from induction of anaesthesia until 48 hours post-operatively. There were no differences in mean age, bypass time or pre-op creatinine in the 36 patients (33 men) who completed the study. 51Cr-EDTA GFR (ml/min/1.73 m2) was measured pre-operatively and on day 5 only. Urinary markers of tubular injury (albumin, N-acetyl glucosaminidase, NAG; retinol binding protein, RBP) were measured pre-operatively, and on days 1, 2 and 5. RESULTS: GFR was preserved equally in both groups. All patients demonstrated significant tubular injury but urinary levels of NAG and RBP were lower in the dopamine group (41%, p=0.057 and 41%, p=0.007, respectively) on the first post-operative day. CONCLUSION: We conclude that low dose dopamine infusion may reduce renal tubular injury following CPB in patients with normal or near normal baseline renal function.

Dialysis improves endothelial function in humans.

BACKGROUND: Circulating inhibitors of endothelial function have been implicated in the pathogenesis of vascular disease in chronic renal failure. The aim of this study was to determine if lowering the plasma concentration of these and other dialysable toxins improves endothelial function. To do this we compared the acute effects on endothelial function of single episodes of haemodialysis with automated peritoneal dialysis. We hypothesized that endothelial function would improve after dialysis, with a greater effect seen after haemodialysis due to more substantial clearance of endothelial toxins per-treatment. METHODS: Subjects with end-stage renal failure undergoing haemodialysis (n=16) or automated peritoneal dialysis (n=14) were investigated. Endothelial function was determined using vascular ultrasound to measure flow-mediated dilatation of the brachial artery and was compared with the dilatation caused by sublingual glyceryl trinitrate. Endothelial function was assessed before and after a single dialysis treatment. Plasma concentrations of the inhibitors of endothelial function, asymmetric dimethyl-l-arginine and homocysteine were measured. Flow-mediated dilatation was expressed as percentage change from basal diameter and analysed using Student's t test. RESULTS: The plasma concentration of circulating inhibitors of endothelial function was reduced after haemodialysis but not peritoneal dialysis. Haemodialysis increased flow-mediated dilatation from 4.0+/-1.0% to 5.8+/-1.2% (P<0.002). These changes persisted for 5 h but returned to baseline by 24 h. Automated peritoneal dialysis had no acute effect on flow-mediated dilatation (5.9+/-1.1% vs 5.4+/-0.8% after, P>0.5). There were no effects of either dialysis modality on dilatation to glyceryl trinitrate. CONCLUSIONS: Short-term reduction of circulating inhibitors of endothelial function by haemodialysis is associated with increased flow-mediated dilatation. These data suggest that dialysable endothelial toxins have deleterious effects on endothelial function that are rapidly reversible.

Outcome in patients with end-stage renal disease following heart or heart--lung transplantation receiving peritoneal dialysis.

BACKGROUND: End-stage renal disease (ESRD) complicates 5--10% of heart and heart--lung transplant patients. We report our experience of peritoneal dialysis (PD) in 17 such patients. METHODS: Between March 1995 and February 1999, 13 heart transplant and four heart--lung transplant patients (11 male, 6 female) joined our PD programme (10 continuous ambulatory PD, seven automated PD). Median time from heart or heart--lung transplantation to ESRD was 9 years (range 1--13 years), and median age at introduction of renal replacement therapy was 51 years (range 23--66 years). The frequency of exit-site infections, peritonitis, and PD survival (including technique failure and death) in the transplant group (TxP) was calculated retrospectively. These were compared with two contemporary control groups: PD patients immunosuppressed for other indications (ISP, n=19) and, all other patients recruited onto the PD programme (NISP, n=132). RESULTS: Median follow-up was 10 months (range 2--27 months) for TxP, 7 months (range 2--29 months) for ISP, and 14 months (range 1--48 months) for NISP groups. The frequency of exit-site infections was similar in each group: 1 in 26 months for TxP; 1 in 30 months for ISP, and 1 in 27 months for NISP (P=NS). The frequency of peritonitis was greater in the TxP group at 1 in 15 months, compared with 1 in 20 months for ISP and 1 in 29 months for NISP (TxP vs NISP, P<0.05). PD failure following infection was 23.5% for TxP, 10.5% for ISP, and 12.9% for NISP. Actuarial PD survival at 24 months was only 25.2% in the TxP group compared with 79% in the NISP group. There were no deaths related to immediate complications of PD. CONCLUSIONS: Increased risk of PD peritonitis and reduced PD survival is reported in this cohort of 17 heart and heart--lung recipients with ESRD. Nevertheless, for patients with severely impaired cardiac function, PD may still offer therapeutic advantage.

Community nephrology: audit of screening for renal insufficiency in a high risk population.

BACKGROUND: The rate of acceptance onto dialysis programmes has doubled in the past 10 years and is steadily increasing. Early detection and treatment of renal failure slows the rate of progression. Is it feasible to screen for patients who are at increased risk of developing renal failure? We have audited primary care records of patients aged 50-75 years who have either hypertension or diabetes, and are therefore considered to be at high risk of developing renal insufficiency. Our aim was to see whether patients had had their blood pressure measured and urine tested for protein within 12 months, and plasma creatinine measured within 24 months. METHODS: This was a retrospective study of case notes and computer records in 12 general practices from inner and greater London. A total of 16,855 patients were aged 50-75 years. From this age group, 2693 (15.5%) patients were identified as being either hypertensive or diabetic, or both. RESULTS: Of the 2561 records audited, 1359 (53.1%) contained a plasma creatinine measured within 24 months, and 11% of these (150) had a value > 125 micromol/l. This equates to a prevalence of renal insufficiency of > 110,000 patients per million in this group. Forty two patients (28%) had been referred to a nephrologist. Of records audited, 73% contained a blood pressure measurement and 29% contained a test for proteinuria within 12 months. CONCLUSIONS: There is a high prevalence of chronic renal insufficiency in hypertensive and diabetic patients. It is feasible to detect renal insufficiency at a primary care level, but an effective system will require computerized databases that code for age, ethnicity, measurement of blood pressure and renal function, as well as diagnoses.

Renal disease and the heart.

Cardiovascular disease is responsible for significant morbidity and mortality in renal failure with increased prevalence of hypertension, left ventricular hypertrophy, ischaemic heart disease and valve disease. Optimum blood pressure control is fundamental to the management of these patients but the role of secondary prevention remains poorly defined.

Pseudo-proteinuria following gelofusine infusion.

Transient massive proteinuria following cardiopulmonary bypass surgery was observed. It was characterized and attributed to post-operative gelofusine infusion. Gelofusine was found to interfere with dye binding but not immunochemical assays of proteinuria. Proteinuria following gelofusine infusion may not reflect underlying glomerular pathology.

Renal nuclear medicine: can it survive the millennium?

Much of the progress in renal nuclear medicine has been driven by technological development, but without rigorous assessment the value of some of these studies has been overestimated. The only tests to achieve gold standard status are the isotopic GFR, the DMSA renogram to detect cortical abnormalities and the captopril renogram when used to define those hypertensive patients who will not benefit from renovascular intervention. Consensus guidelines must be followed and routine protocols for combination tests must be developed, but even so isotopic renography is likely to be overtaken by competing technologies which can provide one test to give simultaneous information about both structure and function.

Cyclosporin nephrotoxicity following cardiac transplantation.

The greatest change in GFR in response to treatment with cyclosporin occurs in the first 3-6 months and the magnitude of the decrement in the first year (or perhaps the first few months) appears to be a vital indicator of future problems. However, the apparent stabilization of renal function, particularly when monitored only by plasma creatinine, can conceal progressive tubulointerstitial injury, and increasing proteinuria is an ominous sign. Although lower doses of cyclosporin and careful monitoring of renal function may be helpful, there is at present no pharmacological intervention to protect or reverse the reduction in GFR that occurs. We believe that the vascular lesion induced by cyclosporin is fundamental, with early and initially reversible cyclosporin-induced vasospasm leading to progressive vascular damage with activation of endothelial cells and increased platelet interactions. Amongst other determinants, the renal response to this vasculopathy will depend on the balance between the presence of vasoactive factors with the vasoconstrictors promoting interstitial fibrosis and the vasodilators inhibiting proliferation. It is likely that the kidneys of heart-transplant recipients are chronically ischaemic and as a consequence their renin-angiotensin systems massively activated, which may further sensitize their kidneys to cyclosporin. Overproduction of angiotensin II, associated with the DD ACE genotype, has already been associated with poor prognosis in diabetic and IgA nephropathy. It is interesting to speculate that this ACE genotype, which is associated with a poor outcome in non-ischaemic heart disease can influence renal sensitivity to cyclosporin and predict the development of morphological injury. Extension of these experimental findings into the clinical arena with a placebo-controlled trial of early introduction of ACE inhibitor therapy in recipients of cardiac transplants would be timely.

Management of bowel obstruction in patients with abdominal cancer.

OBJECTIVE: To determine the value of operation in patients with bowel obstruction caused by recurrent abdominal cancer. DESIGN: Retrospective case review. SETTING: The University of Connecticut Health Center, Farmington. PATIENTS: Ninety-eight patients admitted with a diagnosis of bowel obstruction and malignant neoplasm between November 1, 1987, and June 30, 1995. RESULTS: Data for 75 patients who developed a bowel obstruction within 5 years of a malignant diagnosis were analyzed. Forty-six patients (61%) were treated operatively and 29 (39%) were treated nonoperatively. The operative group included 32 patients (70%) whose obstruction was caused by carcinomatosis; 6 (19%) of these 32 patients had had at least 1 episode of previous obstruction requiring hospitalization. They had a 22% in-hospital mortality, stayed an average of 21 days in the hospital, and survived 7 +/- 6 months (mean +/- SD) after discharge; 5 (16%) had at least 1 episode of postoperative obstruction that required hospitalization. After discharge from the hospital, 53% had an excellent or good quality of life (assessed retrospectively). Of the 29 patients in the nonoperative group, 16 (55%) had carcinomatosis. These 16 patients had a 38% in-hospital mortality (6 of 16), stayed an average of 10 days in the hospital, and survived a mean of 13 +/- 9 months; 3 (19%) had at least 1 episode of recurrent obstruction requiring hospitalization. After discharge from the hospital, 6 (37%) had an excellent or good quality of life. CONCLUSION: The value of operative intervention for bowel obstruction in patients with cancer is derived from the possibility of a benign cause, not alleviation of the consequences of carcinomatosis.

The true clinical significance of renography in nephro-urology.

Isotopic renography is a non-invasive technique used routinely by the clinician to provide information about kidney structure and function. Whilst there is no doubt of its value in the accurate measurement of glomerular filtration rate and in the detection of parenchymal abnormalities, its role in the diagnosis of renovascular disease (especially in patients with renal insufficiency), the exclusion of obstruction and the evaluation of the patient with either acute renal failure or renal transplant dysfunction remains unproven. In part, this reflects a failure to standardise protocols and rigorously evaluate diagnostic techniques. Recent developments in ultrasound, computerised X-ray tomography and nuclear magnetic resonance now present the clinician with rival techniques and emphasise the need for the clinical development of isotopic renography.

Pre-conditioning with adenosine leads to concentration-dependent infarct size reduction in the isolated rabbit heart.

Adenosine (ADO) has a cardioprotective effect in ischemia-reperfusion injury when administered both prior to ischemia and during reperfusion. ADO has also been implicated in the mechanism of ischemic pre-conditioning. The aim of this study was to investigate whether there was a concentration-response between the administration of ADO prior to ischemia-reperfusion and reduction in subsequent infarct size. Rabbit isolated perfused hearts were subjected to 45 min ischemia and 180 min reperfusion following pre-treatment with either Krebs Henseleit buffer alone or buffer containing ADO at a range of concentrations (3 micro M-100 micro M) for 5 min followed by 5 min perfusion with buffer. Infarct/risk ratios were significantly reduced in hearts pre-perfused with higher (> 3 micro M) concentrations of ADO (Control, 58.5 +/- 1.5%; 3 micro M ADO, 51.6 +/- 3.0% ; 6 micro M ADO, 44.1% +/- 2.0%; 10 micro M ADO, 33.3 +/- 1.9%; 20 micro M ADO, 26.6 +/- 0.9%; 50 micro M ADO, 21.6 +/- 3.5%; 100 micro M ADO, 23.0 +/- 0.6%). We conclude that pre-treatment with ADO leads to a concentration-dependent reduction in infarct size.

Nitric oxide contributes to tissue injury in mercuric chloride-induced autoimmunity.

Recent data has suggested a role for nitric oxide (NO) both in the induction of immunity and as an effector of tissue injury in experimental models of inflammation. In this study, we have tested the efficacy of two inhibitors of NO synthase, NG-monomethyl-L-arginine (L-NMMA) and aminoguanidine (AG), to modify the autoimmune leucocytoclastic necrotizing vasculitis which develops following the administration of mercuric chloride (HgCl2) to the Brown Norway rat. Neither agent affected the induction of autoimmunity as judged by plasma IgE titres or the degree of tissue neutrophil infiltration; however, L-NMMA did significantly attenuate tissue injury scores. We conclude that inhibition of NO synthase does not influence the induction of autoimmunity by HgCl2, but that NO does contribute to the development of tissue injury in this experimental model.

Inhibition of nitric oxide synthesis reduces infarct size by an adenosine-dependent mechanism.

BACKGROUND: Nitric oxide (NO) is both a potent endogenous vasodilator with potential to attenuate ischemia-reperfusion injury and a mediator of tissue injury. The aim of the present study was to investigate the mechanism by which prior inhibition of NO synthesis can lessen ischemia-reperfusion injury in the isolated rabbit heart. METHODS AND RESULTS: We examined the effects of inhibition of NO synthesis on infarct size using a model of coronary artery ligation in isolated rabbit hearts perfused at a constant flow rate of 35 mL/min. Infarct size averaged 65% of the zone at risk after 45 minutes of ischemia and 180 minutes of reperfusion. The addition of 30 mumol/L NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, to the perfusate reduced the infarct-to-risk (I/R) ratio to an average of 41% (P < .05 versus control). This effect was abolished by pretreatment with 75.5 mumol/L 8-p-sulfophenyl theophylline (SPT), an adenosine receptor antagonist (I/R ratio, 63%). Ischemic preconditioning (5 minutes of ischemia and 10 minutes of reperfusion) before 45 minutes of ischemia and 3 hours of reperfusion reduced the I/R ratio to an average of 21%, and this was not augmented by pretreatment with L-NAME (I/R ratio, 20%). However, all protection due to preconditioning and L-NAME was lost in hearts pretreated with SPT (I/R ratio, 59%). In a separate set of experiments, adenosine concentration in the coronary perfusate and myocardial lactate concentrations were measured. Treatment with L-NAME increased the average adenosine concentration in the perfusate from 5.7 mumol/L per 100 g of heart (control) to a peak of 24.0 mumol/L per 100 g of heart; however, there was no effect on average myocardial lactate concentration (control, 4.6 mumol/g dry wt; L-NAME, 5.5 mumol/g dry wt). In contrast, after 5 minutes of global ischemia, the average adenosine concentration peaked at 139.0 mumol/L per 100 g of heart, and the average myocardial lactate concentration increased to 27.1 mumol/g dry wt. CONCLUSIONS: Infarct size limitation after inhibition of NO synthesis shares a common mechanism with that of ischemic preconditioning and is dependent on the release of adenosine. However, in this model, adenosine release after inhibition of NO synthesis is not secondary to myocardial ischemia. The protection of the heart against ischemic injury by adenosine appears to be concentration dependent.