The prevalence of vitamin D abnormalities in South Asians with type 2 diabetes mellitus in the UK.

BACKGROUND: The high prevalence of both hypovitaminosis D and type 2 diabetes (T2DM) in the Asian community is well recognised, but the impact of diabetes on vitamin D status and vice versa, has not been well reported. AIMS: To determine the prevalence of hypovitaminosis D in Asian patients with T2DM and its impact on glycaemic control. METHODS: A cross-sectional study was conducted in a tertiary referral centre in the UK. Two hundred and ten Asian patients aged more than 40 years were included (170 with and 40 without T2DM). Each had a standard bone profile (serum calcium, phosphate and alkaline phosphatase), serum parathyroid hormone and 25-hydroxycholecalciferol. RESULTS: The prevalence of low serum 25-hydroxyvitamin D (< 50 nmol/l) was high in the group as a whole (> 80%) and more common in diabetics compared with controls (83% vs. 70%; p = 0.07). This was particularly so in men (82.5% vs. 57.9%; p = 0.02). HbA1c was higher in women with vitamin D deficiency (< 12.5 nmol/l) (8.11 +/- 1.11% vs. 7.33 +/- 1.32%, p = 0.046). In logistic regression analysis, T2DM was an independent predictor of hypovitaminosis D. In linear regression analysis, vitamin D deficiency was independently related to HbA1c in women with T2DM. CONCLUSIONS: Hypovitaminosis D remains a major public health issue in the Asian population and is exaggerated in patients with T2DM. The fact that vitamin D deficient women had higher HbA1c levels raises the possibility that vitamin D replacement may improve glycaemic control.

Detection of impaired glucose tolerance and undiagnosed type 2 diabetes in UK South Asians: an effective screening strategy.

AIM: We tested a stepwise, community-based screening strategy for glucose intolerance in South Asians using a health questionnaire in conjunction with body mass index (BMI). Anthropometric measurements (waist and hip circumference, sagittal diameter and percentage body fat) were then conducted in a hospital setting followed by an oral glucose tolerance test (OGTT) to identify subjects at the highest risk and analyse the factors predicting that risk. METHODS: A health questionnaire was administered to 435 subjects in a community setting and BMI was measured. Subjects were graded by a risk score based on the health questionnaire as high, medium and low. Subjects with high and medium risk scores and a representative sample of those with low scores had anthropometric measurements in hospital followed by an OGTT. In total, 205 (47%) of the subjects had an OGTT performed. RESULTS: In total, 48.7% of the subjects tested with an OGTT had evidence of glucose dysregulation: 20% had diabetes and 28.7% had impaired glucose tolerance (IGT). Logistic regression model explained 49.1% of the total variability. The significant predictors of diabetes and IGT were Blood Glucose Monitoring Strips (BMI), random blood glucose (BM), sibling with diabetes and presence of diagnosed hypertension or ischaemic disease. Most of these predictors along with other heredity diabetes factors create a composite score, with high predictability, as the receiver operating curve analysis shows. CONCLUSION: We describe a simple, stepwise strategy in a community setting, based on a health questionnaire and anthropometric measurements, to explain about 50% of cases with IGT and diabetes and diagnose about 50% of cases from the population screened. We have also identified factors that predict the risk.

Central pontine myelinolysis following 'optimal' rate of correction of hyponatraemia with a good clinical outcome.

Central pontine myelinolyis (CPM), an acute demyelinating condition of the brain stem, is a recognized complication of the treatment of patients with chronic hyponatraemia (hyponatraemia >48 h), particularly in those who abuse alcohol. The risk of CPM is believed to be associated with a rapid (>8 mmol/L/day) correction of the serum sodium concentration, which is said to lead to an osmotically-induced demyelination. CPM is also commonly believed to have a poor, and often fatal, outcome. We report the case of a 37-year-old female alcoholic patient who presented following a collapse, and who was hyponatraemic (serum sodium concentration 105 mmol/L). The rate at which the serum sodium concentration was corrected to normal was less than the 8 mmol/L/day guideline, but nonetheless she developed the clinical and radiological features of CPM. She made a good neurological recovery, however, and was able to be discharged from hospital. CPM does not necessarily have a bleak prognosis, and may occur even with optimal rates of correction of the serum sodium concentration. Clinicians should recognize that the outcome of CPM is not inevitably poor, and the complication may occur despite appropriate management. It is possible that CPM is a complication of the hyponatraemia itself, rather than the treatment of the biochemical disturbance.

Serum resistin is associated with C-reactive protein & LDL cholesterol in type 2 diabetes and coronary artery disease in a Saudi population.

AIMS: Resistin is an adipocyte-derived factor implicated in obesity-associated type 2 diabetes (T2DM). This study examines the association between human serum resistin, T2DM and coronary heart disease. METHODS: One hundred and fourteen Saudi Arabian patients (male: female ratio 46:68; age 51.4 (mean +/- SD)11.7 years; median and range: 45.59 (11.7) years and BMI: 27.1 (mean +/- SD) 8.1 Kgm2 median and range: 30.3 (6.3) were studied. Serum resistin and C-reactive protein (CRP), a marker of inflammation CRP levels, were measured in all subjects. (35 patients had type 2 diabetes mellitus (T2DM); 22 patients had coronary heart disease (CHD). RESULTS: Serum resistin levels were 1.2-fold higher in type 2 diabetes and 1.3-fold higher in CHD than in controls (p = 0.01). In addition, CRP was significantly increased in both T2DM and CHD patients (p = 0.007 and p = 0.002 respectively). The use of regression analysis also determined that serum resistin correlated with CRP levels (p = 0.04, R2 0.045). CONCLUSION: The findings from this study further implicate resistin as a circulating protein associated with T2DM and CHD. In addition this study also demonstrates an association between resistin and CRP, a marker of inflammation in type 2 diabetic patients.

Canada-Cronkhite syndrome in an 82-year-old woman.

An 82-year-old woman with the Canada-Cronkhite syndrome is described. The patient was unusual because of her age at presentation, favorable response to treatment with steroids and feeding jejunostomy, and associated hypothyroidism.

Relation of endothelium, thrombogenesis, and hemorheology in systemic hypertension to ethnicity and left ventricular hypertrophy.

Although the arterial tree is exposed to increased pressure in hypertensive patients, paradoxically, the complications of hypertension (heart attacks, stroke) are mainly thrombotic rather than hemorrhagic. Patients with left ventricular (LV) hypertrophy are at high risk of the complications of hypertension. We performed a cross-sectional study of 178 patients attending a hypertension clinic in a city center teaching hospital, and measured plasma levels of the soluble adhesion molecule P-selectin (associated with platelet activity/function and atherosclerosis), the von Willebrand factor (vWf; a marker of endothelial dysfunction), fibrin D-dimer (an index of thrombogenesis), plasminogen activator inhibitor (PAI, an index of fibrinolysis), lipoprotein(a) (Lp(a), associated with thrombogenesis and atherogenesis) and hemorheological indexes (fibrinogen, hematocrit, plasma viscosity, hemoglobin) in patients with essential hypertension, in whom the LV mass and LV mass index were determined using echocardiography. The 178 patients (86 men, mean age 54 +/- 15 years) were compared with 47 normotensive healthy controls (aged 56 +/- 20 years). Hypertensive patients had higher P-selectin, PAI, vWf, fibrin D-dimer, Lp(a), plasma fibrinogen, and plasma viscosity when compared with controls. Black hypertensive patients had higher Lp(a) levels and LV septal and posterior wall thickness on echocardiography, but lower plasma PAI levels. Patients with LV hypertrophy (defined as a LV mass index > 134 g/m2 in men or > 110 g/m2 in women) had higher plasma fibrinogen compared with those without LV hypertrophy. Systolic blood pressures were significantly correlated to age, plasma viscosity, plasma fibrinogen, and vWf. Diastolic blood pressures were significantly correlated with age and plasma fibrinogen. Fibrinogen levels were correlated with LV mass, LV mass index, left atrial size, plasma viscosity, and vWf. Fibrin D-dimer levels were significantly correlated with vWf and fibrinogen levels. Thus, hypertensive patients have high plasma fibrinogen levels, thrombogenesis, and impaired fibrinolysis (as indicated by high D-dimer and PAI levels, respectively), platelet activation (raised soluble P-selectin), and endothelial dysfunction (high vWF). The high plasma fibrinogen levels were related to blood pressures, LV mass index (and LV hypertrophy), and left atrial size. These abnormalities in hemorheologic factors and markers of thrombogenesis and endothelial function may act synergistically to increase the risk of thrombogenesis and atherosclerosis in hypertensive patients.

A pilot study of homocyst(e)ine levels in essential hypertension: relationship to von Willebrand factor, an index of endothelial damage.

An interaction between homocyst(e)ine and the endothelium in hypertensive patients may promote thrombogenesis and atherogenesis, leading to adverse cardiovascular events. We hypothesized that homocyst(e)ine levels are abnormal in patients with essential hypertension, and that this may be related to an adverse effect on the vascular endothelium. Accordingly, we compared plasma levels of homocyst(e)ine and von Willebrand factor (marking endothelial damage) in 83 patients (43 men; mean age 54 +/- standard deviation 15.9 years) with essential hypertension (> 160/90 mm Hg), with levels in 25 healthy normotensive controls (13 men; mean age 56+/-11.8 years). Baseline levels of the markers and other clinical indices were then related to adverse cardiovascular events at follow-up. Plasma homocyst(e)ine (P = .0001) and von Willebrand factor (P = .031) levels were significantly higher in hypertensives compared to controls. After a mean follow-up of 76 patients for 45 months (range, 1 to 66 months), 17 subjects experienced an end point of either cardiovascular death (n = 10) or adverse cardiovascular event (n = 7). Comparing these 17 with the 59 free of an end point, the former were older (P = .0002) and had a longer duration of known hypertension (P = .018). There was a nonsignificant trend toward higher median plasma homocyst(e)ine levels in the patients sustaining a vascular end point (P = .07). In this pilot study, we suggest that essential hypertension may be associated with increased plasma homocyst(e)ine levels, but that this amino acid is unrelated to endothelial damage (von Willebrand factor), clinical indices, or prognosis.

Aortofemoral bypass grafting: a reappraisal.

Aortic bypass grafting was performed in 100 consecutive patients with disabling manifestations of aortoiliac arterial occlusive disease. There were no operative deaths, graft infections, false aneurysms, or aortoduodenal fistulas. Of those patients whose superficial femoral arteries were patent, 95% had a good or excellent immediate functional result that was maintained in 89% on late follow-up. Of those whose superficial femoral arteries were occluded, 83% had a similar immediate result and 70% maintained this improvement. Graft limb patency was 89% after 36 months. Additional distal arterial reconstructions were ultimately required in 9% of all limbs, resulting in a good to excellent functional outcome for 93% of all our patients. We believe aortofemoral grafting remains the best method for the correction of aortoiliac occlusive disease.

Lipoprotein (a) and vascular disease: thrombogenesis and atherogenesis.

Lipoprotein (a) [Lp(a)] has been recognized for nearly 30 years, and increasingly, associated with the processes of atherogenesis and thrombogenesis. Despite this, the physiological and pathological function (and factors that influence levels) of Lp(a) remain largely unknown. Most experimental evidence supporting the mechanisms of vascular disease, thrombogenesis and atherogenesis have been generated in vitro, and to date, no in vivo confirmation exists. There is also a lack of sound evidence for Lp(a) as a risk factor in prospective as opposed to case-controlled studies. A fuller understanding of Lp(a) is still required in the molecular biology of atherogenesis and thrombogenesis.

Immediate operation for ectopia cordis.

Forty-one infants with thoracoabdominal ectopia cordis have been reported to date; 9 of them survived. Among the patients with an omphalocele as the abdominal wall defect, however, only 2 survived. Death in this group of patients occurred almost exclusively as a consequence of either attempted coverage of the heart or secondary to the associated intracardiac lesion. We report here the case of a patient recently treated in whom coverage with a temporary Silastic prosthesis protected the exposed heart from infection and rupture of the sac, thus permitting full cardiac investigation before operation.

Enteric alpha-1-antitrypsin loss and comparison with Okokit II and Haemoccult for the detection of colorectal cancer.

Faecal samples from patients with symptomatic colorectal cancer (n = 19) and from control subjects (n = 54) were analysed for alpha-1-antitrypsin (A1AT) and compared with Haemoccult and Okokit II. A1AT was also measured in paired samples of normal colonic mucosa and cancer tissue (n = 16) and in media from four human colorectal cell lines (COLO 320 DM, SW620, HT29, LS 174T). Faecal A1AT concentrations were greater than controls (P < 0.0001) and detected 12 (63%) patients with cancer compared to 10 (53%) by Okokit II and 7 (37%) by Haemoccult (P > 0.05). A1AT concentrations from colonic mucosa (median, range: 0.46, 0.17-0.79 mg/g wet wt) were greater (P = 0.01) than cancer tissue (0.29, 0.13-0.74 mg/g wt wt). Adjusting for albumin, A1AT concentrations from mucosa (12.0, 3.8-32.2 mg/g albumin) remained greater (P = 0.003) than for cancer tissue (5.9, 2.4-21.4 mg/g albumin). A1AT was not detected in any of the cell-line media. The most likely mechanisms for increased faecal A1AT concentrations, apart from increased blood loss, are increased cell turnover or leakage from epithelial tight junctions. The use of faecal A1AT measurement for the detection of colorectal cancer deserves further assessment.

Transvaginal ultrasonography.

Transvaginal ultrasonography has provided new anatomic and pathophysiologic information about the female pelvis. Because of probe proximity to the organ of interest and higher insonating frequency, resolution is dramatically improved. Problems previously encountered during transabdominal scanning, such as obesity, bowel gas, and a retroverted uterus, no longer preclude accurate diagnosis. Patient acceptance is nearly universal. Physiologic information concerning the endometrium and ovarian follicles has improved infertility diagnosis and treatment. Hormonal and vascular Doppler changes can be correlated with cyclic endometrial patterns and follicle size. Oocyte retrieval, management of pre-existing inflammatory disease, and treatment of complications of pregnancy are easier and safer with a transvaginal approach. Uterine malformations, leiomyomas, and cancers are more easily detected in premenopausal and postmenopausal women. The documentation of early intrauterine or ectopic pregnancy has decreased maternal morbidity and mortality. Tube-sparing procedures with preservation of reproductive potential are now more commonly employed due to earlier recognition of unruptured tubal pregnancy. Interventional TVS has led to improved recognition and treatment of pelvic cysts and abscesses and multiple pregnancy. Chorionic villous sampling can be performed more easily without the need for anesthesia, with adequate tissue obtained.

Effects of dietary sodium substitution with potassium and magnesium in hypertensive type II diabetics: a randomised blind controlled parallel study.

We have previously demonstrated that modest sodium restriction has a hypotensive effect in hypertensive diabetic subjects. A randomised blind controlled study has therefore been performed to study the effect of replacement of added salt intake using a salt substitute (50% NaCl, 40% KCL, 10% Mg2+, supplied by Cederroth, Sweden), compared to added whole salt intake over a 9 month period of 40 hypertensive Type II diabetic subjects (mean age 62.5 +/- 7.8 years; 24 males and 16 females). After 3 months, there was a significant reduction in systolic blood pressure (SBP) in the salt substitution group (163.2 +/- 24.2 to 153.6 +/- 20.8 mm Hg; P < 0.03) which was maintained at 9 months, when compared to the whole salt group (151.5 +/- 20.6 vs 173 +/- 18.9 mm Hg; P < 0.05). No significant changes were observed in mean weight, fasting lipid or insulin levels or diabetic control (measured by glycosylated haemoglobin). A greater number of patients were withdrawn during the study period owing to consistent BP > 160/95 in the whole salt group (n = 10) compared to salt substitute (n = 4). No significant changes were observed in diastolic pressure, 24-h urine sodium or magnesium excretion, but urine potassium was significantly increased in the salt substitute group (58.8 to 77.3: P < 0.05). The results of this study suggest that substitution of sodium, by potassium and magnesium, produces a clinically significant reduction in SBP in hypertensive Type II diabetic patients, and should be a useful antihypertensive therapy in this patient group.

The human red blood cell glyoxalase system in diabetes mellitus.

Methylglyoxal and other alpha-oxoaldehydes are formed from glycolytic intermediates and may be involved in the development of diabetic microangiopathy. Glyoxalase I and glyoxalase II metabolise methylglyoxal to D-lactic acid, via the intermediate S-D-lactoylglutathione. The activities of the glyoxalase enzymes and the concentrations of methylglyoxal and S-D-lactoylglutathione were measured in erythrocytes of 45 control and 85 diabetic subjects (41 with retinopathy and 44 uncomplicated). The concentration of S-D-lactoylglutathione was increased in diabetic patients vs. controls (21.4 +/- 9.3 vs. 12.4 +/- 4.8 mumol/l, P less than 0.001), as was methylglyoxal (3.6 +/- 2.3 vs. 1.4 +/- 0.2 mumol/l, P less than 0.001). There were no significant differences in the activities of glyoxalase I and glyoxalase II between diabetic patients and controls. For insulin-dependent patients only, those without retinopathy had a higher activity of glyoxalase II than those with retinopathy (P less than 0.05). A group of age- and duration-matched insulin-dependent diabetic patients with retinopathy also had a higher activity of glyoxalase I compared with a group of diabetic patients without retinopathy (P less than 0.025). This study provides evidence for elevated concentrations of oxoaldehydes in diabetes mellitus which might have pathogenic significance.

Cardiovascular risk assessment in patients with retinal vein occlusion.

AIM: Patients with retinal vein occlusions (RVO) are at increased risk of cardiovascular disease (CVD). The risk of future CVD was determined using the Framingham algorithm and this risk estimate was used to guide decisions about preventative treatment for CVD in RVO patients. METHODS: 107 unselected RVO patients were studied. After excluding 18 patients because of age, missing data, or pre-existing cardiovascular disease, the calculated coronary heart disease risks (cCHDR) and calculated cardiovascular disease risks (cCVDR) were calculated on the 89 remaining and compared with both the standardised risk and the published incidence of CHD in England by t test or chi(2) test. RESULTS: The mean 10 year cCVDR was significantly higher than the Framingham standardised risk for all RVOs (20.6% (1.2%) v 15.7% (1.1%), p = 0.009) and female RVOs (17.8% (1.2%) v 12.7% (1.0%), p = 0.022) in particular. The 10 year cCHDR, compared to the actual incidence of CHD in England between the ages of 30 and 74 years, was > 15% in twice as many males than expected (62% v 28%, p <0.0001). This rose to almost six times when cCHDRs greater than 30% were compared (17% v 3%, p = 0.002). There was a fourfold increase in the proportion of female RVO patients with a cCHDR above 15% (40% v 9%, p <0.0001) and at a cCHDR of 30% and above (10% v 0%, p = 0.004). There were also significant differences in the cCHDR between central and branch RVO (both sexes). The branch form of RVO (BRVO) having higher cCHDRs because of systolic hypertension (164.1 (21.6) mm Hg v 149.5 (23.5) mm Hg, p = 0.003) and age (61.7 (8.3) years v 56.7 (10.6) years, p = 0.017). CONCLUSIONS: RVO is the presenting complaint in a group of patients at increased risk of CVD and is in agreement with the long term follow up data demonstrating an increased mortality from CVD in patients with RVO. The Framingham algorithm can accurately determine the cCHDR (or cCVDR) to assist the clinician in deciding who to treat in accordance with the Joint British Societies' guidelines, with particular regard to hypertension, lipid lowering, and the use of aspirin therapy.

What surface of the intestinal epithelium is effectively available to permeating drugs?

A mathematical model is presented which examines the extent to which the intestinal epithelium is accessed by drug molecules. Morphological information from the literature for the jejunum, ileum, and colon of the rat and for human jejunum was incorporated. Perturbation theory was used to derive the limiting cases for total access to the entire epithelial surface, for transport by diffusion and by diffusion with convection, respectively. A parameter gamma = square root of (Ph2)/(Db) was identified to provide a measure of the ability of drug molecules to access the entire epithelial surface down to the crypt wells, where P is the cell permeability, D the aqueous diffusion coefficient, h the channel depth between the villi, and b is half the width of the idealized intervillous channel. When gamma << 1, diffusion is not a limitation and the entire surface is fully utilized for absorption of drug. This condition arises with drugs of low permeability and is more likely to be met with colonic than small intestinal epithelium. When gamma >/= 1, diffusion becomes a limitation and then not all of the epithelial surface is functionally accessible to drug molecules, a condition most likely to prevail with drugs of high permeability traversing the jejunum. Furthermore, water flux per se is predicted to have relatively little influence on enhancing surface accessibility. This simple, but quantitative approach showed that the ranking order of permeability jejunum >ileum> colon for low permeable drugs can at least in part be explained by the differences in surface amplification between these different epithelial regions. The analysis also indicates that for highly permeable drugs extreme caution should be exercised in extrapolating permeability measurements in vitro across various preparations and to events in vivo.

Burn and trauma associated proteinuria: the role of lipid peroxidation, renin and myoglobin.

Ten trauma patients and 13 burns patients were studied intensively for the first 36 h and subsequent 6 days post injury in order to investigate the mechanism of trauma and burn associated proteinuria. Burns patient's initial maximum proteinuria occurred between 4 and 8 h post injury, whilst trauma patients showed greatest proteinuria within 4 h. In both groups coexisting myoglobinuria or marked elevation of serum renin activity was not found during the first 36 h. Following admission serum lipid peroxides rose in burns patients reaching a maximum between 2 and 8 h following injury, after which levels fell rapidly; in contrast trauma patient's values were initially within normal limits, but rose sharply after 12 h with peaks occurring between 16 h and 7 days post injury. Some patients within both groups showed a recurrent protein leak 2 to 5 days post injury. The data suggest that myoglobinuria or raised renin levels do not play an important role in trauma associated proteinuria.

Detection of colorectal cancer by faecal alpha 1-antitrypsin.

Alpha 1-antitrypsin was measured in 5-day faecal collections from patients with colorectal cancer or adenomatous polyps and a symptomatic control group. Collections were homogenized and lyophilized prior to measurement of alpha 1-antitrypsin by radial immuno-diffusion. Colorectal cancer dry weight concentrations were significantly higher than the symptomatic control results, with 57% having results greater than 95% normal values of this control group. There was no significant difference between adenomatous polyp dry weight concentrations and symptomatic control results. Wet weight concentrations were calculated from wet/dry ratios. Colorectal cancer wet weight concentrations were significantly higher than symptomatic control results with 48% having results greater than 95% normal values of this control group. Alpha 1-antitrypsin was also measured in non-lyophilized samples from an asymptomatic control group (n = 39). Colorectal cancer wet weight concentrations were significantly higher than asymptomatic control results, with 62% having results greater than 95% normal values of this control group. Faecal alpha 1-antitrypsin measurement deserves further assessment for use in detecting colorectal cancer.

A non-isotopic method for estimating 11 beta hydroxysteroid dehydrogenase activity in vivo.

11 beta-hydroxysteroid dehydrogenase (11 beta HSD) has both dehydrogenase (11 beta DH) and reductase (11 beta R) activities, which catalyse the interconversion of cortisol and cortisone, and prednisolone and prednisone. This enzyme confers specificity on the mineralocorticoid receptor by local oxidation of cortisol to cortisone. Using radiolabelled cortisol 11 beta HSD activity has been shown to be lower in some cases of essential hypertension. This study investigated a novel approach to estimating 11 beta HSD activity in vivo. Plasma steroid kinetics were investigated following oral hydrocortisone (a substrate for 11 beta DH) and prednisone (a substrate for 11 beta R) in five normotensive volunteers after dexamethasone suppression of endogenous steroid production. This approach was evaluated by inducing partial deficiency of 11 beta HSD in the volunteers who took liquorice (to inhibit 11 beta DH) and then carbenoxolone (to inhibit both 11 beta DH and 11 beta R). The ratio of cortisol to prednisolone (formed from prednisone) provided a measure of the activity of both 11 beta DH and 11 beta R. At 75 min after the steroid bolus the ratio increased from 1.1 (0.6-1.3) (median, range) under control conditions to 1.2 (0.8-1.7) after liquorice (P = 0.01, n = 5), and 2.0 (1.3-5.9) after carbenoxolone (P = 0.02, n = 5). It may therefore be applied to the measurement of 11 beta HSD activity in vivo in large numbers of hypertensive patients without the use of radioisotopes.

Retinol binding proteinuria and phosphaturia: markers of paracetamol-induced nephrotoxicity.

The occurrence of hypophosphataemia in paracetamol overdose suggests that nephrotoxicity is common, impaired renal tubular reabsorption of phosphate indicating renal damage. To investigate the potential nephrotoxicity of paracetamol, we studied 148 consecutive patients with paracetamol overdose. Serial clinical and biochemical measurements were made, and a fasting overnight urine collection was obtained for creatinine (Cr), phosphate and retinol-binding protein (RBP) determination. Renal threshold phosphate concentration (TmPO4/GFR) was determined from urinary parameters by an established nomogram. The degree of hypophosphataemia correlated with the severity of overdose, and with TmPO4/GFR. The median RBP/Cr ratio was higher in those patients exhibiting biochemical hepatotoxicity compared with those without hepatotoxicity, in whom median RBP/Cr was not significantly higher than controls. Within the group of patients showing biochemical hepatotoxicity, there was a correlation between log RBP/Cr and TmPO4/GFR. RBP/Cr ratio is a less sensitive marker of renal tubular toxicity than phosphaturia in these patients, and may indicate a different mechanism of toxicity.