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Bleeding and thrombosis are well known major causes of morbidity and mortality in patients with myeloproliferative disorders (MPD) but the relationship between these clinical events and the commonly found platelet function abnormalities have not been established. In this study we performed simultaneous laboratory evaluations in 54 patients with MPD to investigate abnormalities in platelet aggregation and cyclooxygenase activity, the latter by using an in vitro aspirin inhibition test; the studies were repeated in 22 patients 1-27 months later. We have found platelet hyper- and hypofunction co-existing in some patients (9/54), and change of platelet function during the course of the disease (7/22) with platelet hypofunction being the only constant abnormality over time. These results may explain the lack of correlation between the clinical events and the limited assessment of platelet function in the hitherto published studies, and also suggest the need for repeated evaluations to properly assess the relative risk for bleeding and thrombosis.

We describe a 31-year-old patient with pure red cell aplasia of pregnancy, successfully managed with regular blood transfusions. In vitro studies showed specific inhibition of day 14 erythroid colonies (BFU-E) using serum and purified immunoglobulin G (IgG) obtained from the patient at diagnosis (before blood transfusion). The inhibition of BFU-E disappeared when haematological remission occurred 3 weeks after delivery and she remains clinically well with a normal haemoglobin 4 years later.

was statistically significantly stronger than with outpatient systolic BP (r=0.25, 95% confidence Background. Left ventricular hypertrophy (LVH ) is both common and an important predictor of risk of interval 0.23-0.27). The same was true for the correla- tion between LVMI and mean 24-h ambulatory dia- death in end-stage renal failure ( ESRF ). In mild to moderate chronic renal failure (CRF ), the timing of stolic BP (r=0.42, 95% confidence interval 0.40-0.44), and outpatient diastolic BP (r=0.22, 95% confidence onset of LVH and the factors involved in its initial development have not been fully elucidated. The pre- interval 0.20-0.24). Conclusions. Twenty-four hour ambulatory BP record- sent study was undertaken to examine the prevalence and potential determinants of echocardiographically ing and echocardiography are required for accurate diagnosis of inadequate BP control and early LVH in determined LVH in this connection, and to compare 24-h ambulatory blood pressure ( BP) recordings with patients with chronic renal impairment, independent determinants of which are hypertension, male sex, BP measured at a previous clinic visit. Methods. From a cohort of 120 non-diabetic patients BMI, and anaemia. who had been attending a nephrology clinic, 118 agreed to participate in the study. Of these we selected for chronic renal failure (CRF ); hypertension; left ventri- analysis 85 stable patients (37 male). Patients with cular hypertrophy ( LVH ) known cardiovascular disease, those with a history of poor compliance with antihypertensive medication, and those in whom such medication had been changed in the previous 3 months were excluded. Clinic BP, Introduction 24-h ambulatory BP, echocardiography, body mass index (BMI ), serum creatinine (SCr), creatinine clear- Cardiovascular disease is the leading cause of death in ance (CrCl ), haemoglobin ( Hb), fasting cholesterol patients on renal replacement therapy (1-3). Left vent- (CHOL), triglyceride TRlGL), plasma glucose, calcium ricular hypertrophy (LVH ) is a strong predictor of (Ca), phosphate ( PO 4 ), alkaline phosphatase (ALK myocardial infarction, cardiac failure, sudden death, PHOS ), parathyroid hormone (PTH ) concentrations, and stroke in patients with essential hypertension and and 24-h urinary protein were assessed in all patients. normal renal function and those with end-stage renal Seventy-seven per cent were on antihypertensive disease ( ESRD) (4-7). LVH is common in ESRD and medication. frequently predates the initiation of dialysis treatment Results. LVH was detected in 16% of patients with (7-9 ), suggesting that the factors responsible may be CrCL >30 ml/min, and 38% of patients with CrCl present in early renal impairment. Information regard

A randomized controlled study of iron supplementation in patients treated with erythropoietin. In view of current uncertainty regarding the optimum route for iron supplementation in patients receiving recombinant human erythropoietin (EPO), a prospective randomized controlled study was designed to investigate this issue. All iron-replete renal failure patients commencing EPO who had a hemoglobin concentration < 8.5 g/dl and an initial serum ferritin level of 100 to 800 µg/liter were randomized into three groups with different iron supplementation: Group 1, i.v. iron dextran 5ml every 2 weeks; Group 2, oral ferrous sulphate 200mg tds; Group 3, no iron. All patients were treated with 25 U/kg of EPO thrice weekly subcutaneously. The hemoglobin concentration, reticulocyte count, serum ferritin, transferrin saturation, and EPO dose were monitored every two weeks for the first four months. Thirty-seven patients entered the study (12 i.v., 13 oral, 12 no iron). The three groups were equivalent with regard to age, sex, and other demographic details. Even allowing for dosage adjustments, the hemoglobin response in the group receiving i.v. iron (7.3 ± 0.8 to 11.9 ± 1.2 g/dl) was significantly greater than that for the other two groups (7.2 ± 1.1 to 10.2 ±1.4 g/dl and 7.3 ± 0.8 to 9.9 ± 1.6 g/dl for Groups 2 and 3, respectively; P < 0.005 for both groups vs. Group 1 at 16 weeks). There was no difference between the groups supplemented with oral iron and no iron. Serum ferritin levels remained constant in those receiving i.v. iron (345 ± 273 to 359 ± 140 µg/liter), in contrast to the other two groups in which ferritin levels fell significantly (309 ± 218 to 116 ± 87 µg/liter and 458 ± 206 to 131 ± 121 µg/liter for Groups 2 and 3, respectively; P < 0.0005 for Group 1 vs. Group 2, and P < 0.005 for Group 1 vs. Group 3 at 16 weeks). Dosage requirements of EPO were less in Group 1 (1202 ± 229 U/kg/16 weeks) than in Group 2 (1294 ± 314 U/kg/16 weeks) or Group 3 (1475 ± 311 U/kg/16 weeks; P < 0.05 vs. Group 1). The results of this study suggest that, even in iron-replete patients, those supplemented with i.v. iron have an enhanced hemoglobin response to EPO with better maintenance of iron stores and lower dosage requirements of EPO, compared with those patients receiving oral iron and no iron supplementation.

Atherosclerotic renal artery stenosis (RAS) is a recognized cause of renal impairment. RAS is often overlooked in unexplained chronic kidney disease (CKD). A retrospective analysis of renal angiograms was performed to determine the prevalence of occult renovascular disease in 64 (M:F, 46:18; ages 21-81 years [median 60 years]) patients with unexplained CKD. Twelve patients had diabetes mellitus (type II: 11) and 43 were smokers. Median serum creatinine was 5.2 mg/dl (range 1.5-10.6 mg/dl). Group A included patients with unexplained CKD and with no risk factors for RAS and Group B had patients with increased risk for RAS. A narrowing of the renal vessel, main artery or branch, by >50% on renal arteriography was used as diagnostic criteria for RAS. 31/64 patients had positive angiographic findings. Thirteen patients had unilateral RAS, 9 had bilateral RAS, 5 had unilateral stenosis with occlusion on the opposite side, 3 had unilateral occlusion and 1 had a solitary kidney with RAS. 19/34 (54%) in Group A and 12/30 (40%) in Group B had a positive renal angiogram. In 10 patients with a rise in serum creatinine on recent introduction of ACE inhibition, 2 had evidence of RAS on renal arteriography. Eleven patients underwent angioplasty and 2 reconstructive surgeries. In 4 patients, blood pressure control improved and anti-hypertensive drug requirements were reduced, whilst renal replacement therapy was postponed in 4, by 2-24 months. In 18 patients, the lesions were not amenable to angioplasty or reconstructive surgery. Four patients did not benefit in any form with intervention. Occult atheromatous renal vascular disease is a common, not readily predictable and potentially correctable etiology of unexplained CKD.

The prevalence of sensorineural hearing loss, measured by pure tone audiometry, was determined in 66 patients with chronic renal failure and threshold changes following haemodialysis were measured in 31 patients. The incidence of hearing loss was 41% in the low, 15% in the middle and 53% in the high frequency ranges respectively. No correlations with weight changes, haematocrit, metabolic bone disease or ototoxic drug history were found. Of 62 ears studied, 38% had a decrease in low frequency threshold after dialysis and 9% had an increase. Threshold in 22/31 ears with pre-existing low frequency loss altered after dialysis with little change in other frequencies and no correlation with weight changes. In conclusion, we find a high incidence of low and high frequency hearing losses in chronic renal failure patients. Fluctuation in low frequencies with dialysis is common. Possible mechanisms include treatment induced changes in fluid and electrolyte composition of endolymph.

The 20210A prothrombin mutation has recently been associated with an increased risk of venous thrombosis, but the mechanism of the increased thrombotic risk in affected persons has not been elucidated. We report on a thrombophilic family in which the proband presented with cerebral vein thrombosis and homozygosity for the 20210A prothrombin mutation as her only identifiable risk factor for venous thrombosis. Extended genotyping of family members revealed seven other affected, but asymptomatic, first-degree relatives (one A/A homozygote and six G/A heterozygotes). Plasma levels of prothrombin, prothrombin fragments 1 + 2 and thrombin-antithrombin complexes were highest in A/A homozygotes, intermediate in G/A heterozygotes and lowest in those with the G/G homozygous normal genotype, while D-dimer levels were elevated only in A/A homozygotes. Our results suggest that the 20210A prothrombin mutation is associated with activation of coagulation and increased thrombin generation, not only in patients with a past history of thrombosis but also in otherwise healthy asymptomatic persons. In a similar fashion to the homozygous factor V Leiden mutation, patients with the homozygous 20210A prothrombin mutation could be at highest risk of thrombosis, as suggested by our patient who presented with unusual thrombosis.

The 20210 G/A prothrombin gene mutation is associated with an increased risk of venous thrombosis but whether there is an association of the mutation with premature coronary artery disease and acute myocardial infarction remains unclear. To further assess the role of the G/A genotype as a risk factor for arterial vascular disease, we performed a case-control study of 644 patients aged less than 50 years with angiographically proven coronary artery disease, 402 of whom had myocardial infarction, and 679 unrelated healthy control subjects aged less than 50 years, randomly selected from the electoral roll. The prevalence of the G/A genotype was 2.5% in patients with coronary artery disease, and 3.2% in control subjects (odds ratio 0.8; 95% confidence interval 0.35 to 1.83). The mutation was not more frequent among patients with a history of myocardial infarction (2.2%, odds ratio 0.7; 95% confidence interval 0.27 to 2.05), and there was no evidence of an interaction between the prothrombin mutation and conventional cardiovascular disease risk factors. There was no association between genotype and extent of angiographic coronary artery disease (p=0.73). We conclude that the 20210 G/A prothrombin gene mutation is not a major risk factor for premature coronary artery disease in our predominantly Caucasian Australian population.

Eighteen patients aged 60-84 years with acute myeloid leukemia were treated with low-dose combination chemotherapy comprising cytarabine, etoposide, and mitozantrone or 6-thioguanine; seven of these patients had a pre-existing myelodysplastic syndrome. Nine patients achieved a complete remission, and five had a partial remission. The duration of survival in these 14 responding patients has ranged from 2+ to 19+ months. Myelotoxicity occurred regularly, with time to recovery (neutrophilsor =0.5 x 10(9)/L, plateletsor =50 x 10(9)/L) from nadir being 10-14 days in 12 of the 14 patients. This novel approach with an overall response rate of 78% appears to be a simple and effective form of therapy for elderly patients.

Background Technetium-99m methoxy isobutyl isonitrile (Tc-99m MIBI) scintigraphy has been reported to be at least as reliable as thallium-technetium subtraction imaging in the preoperative localization of hyperplastic parathyroid glands in patients with renal failure. Reports have suggested that 50% of glands can be identified correctly by this method. The aim of this study was to improve on previous results and demonstrate that Tc-99m MIBI imaging has an important place in the preoperative work-up of these patients. Methods Eighteen patients on renal replacement therapy were studied. All had tertiary hyperparathyroidism and had Tc-99m MIBI imaging prior to parathyroidectomy. A refined reporting method was employed. The imaging results were compared to the subsequent surgical and histological findings. Results In the 12 patients in whom serum parathyroid hormone levels fell postoperatively to within or below the normal range, 38 of 46 glands (82.6%) were correctly identified and located in the correct quadrant of the thyroid gland. There were two false positive results where the imaging predicted glands not subsequently found by the surgeon. In the patients who had post-operative hyperparathyroidism, repeat Tc-99m MIBI imaging was able to locate accurately the site of the residual parathyroid tissue. Conclusions Tc-99m MIBI imaging is able to identify more than 80% of hyperplastic parathyroid glands in renal failure patients if this reporting process is used, and locate them in the correct quadrant of the thyroid gland. Tc-99m MIBI imaging is of particular value when re-exploration of the neck is required for post-parathyroidectomy hyperparathyroidism. These results represent a significant improvement on the sensitivity of this imaging technique when compared to previous published data.

AIMS--To differentiate between reinfection and relapsing infection with Staphylococcus epidermidis in a middle-aged woman with defective opsonisation and procidin function in serum. METHODS--Microbiological typing was done by biotyping, phage typing, and polyacrylamide gel electrophoresis of radiolabelled bacterial proteins (radioPAGE method). Polymorphonuclear cell function was assessed in vitro by phagocytosis and killing of Candida albicans; measurement of neutrophil random locomotion and chemotaxis; reduction of nitroblue tetrazolium after stimulation by opsonised Candida and a radiometric saccharomyces opsonisation assay. The effect of plasma infusions on opsonic activity was assessed by chemiluminescence using control polymorphonuclear leucocytes with a laboratory strain of S epidermidis opsonised with either patient or control serum. RESULTS--Recurrent reinfection with different strains of Staphylococcus epidermidis rather than relapsing infection was confirmed as having occurred by typing bacterial strains. The RadioPAGE method detected all the S epidermidis strains involved in this patient's illness. The patient's serum was shown to be defective in both opsonin and procidin function. The defects were correctable in vitro by the addition of normal serum. Clinical recovery occurred after repeated infusions of normal fresh frozen plasma and prolonged antibacterial treatment; antibacterial treatment alone was insufficient. CONCLUSIONS--The radioPAGE method is useful in distinguishing recurrent reinfection with S epidermidis from relapsing infection with this organism. Elucidation of the nature of, and underlying predisposition to, infection in the patient studied allowed a rational treatment plan of plasma infusion combined with antibacterial treatment to be devised which ultimately proved successful.

1. Twelve patients receiving haemodialysis for end-stage renal failure were studied at a single dialysis session. Platelet cytosolic calcium concentration, plasma ionized calcium concentration and serum parathyroid hormone concentration were measured before dialysis, mid-dialysis and 30 min after dialysis. 2. Plasma ionized calcium concentration increased towards dialysate calcium concentrations, falling insignificantly after cessation of dialysis. Serum parathyroid hormone concentration fell by 39% during dialysis, with incomplete recovery afterwards. There was no overall change in platelet cytosolic calcium concentration. 3. Patients were divided into two subgroups: low parathyroid hormone (serum parathyroid hormone concentration < 10 pmol/l) and high parathyroid hormone (serum parathyroid hormone concentration > 10 pmol/l). Before dialysis, values of platelet cytosolic calcium concentration or plasma ionized calcium concentration were not statistically different between the subgroups, but the platelet cytosolic calcium concentration was higher in the high-parathyroid hormone subgroup during and after dialysis. 4. Before haemodialysis there was a linear correlation between plasma ionized calcium concentration and platelet cytosolic calcium concentration, which disappeared during dialysis. In contrast, there was no relationship between serum parathyroid hormone concentration and platelet cytosolic calcium concentration before dialysis, but after dialysis a hyperbolic relationship was evident. 5. These results suggest that uraemic toxins may interfere with cytosolic calcium homoeostasis, allowing passive diffusion of extracellular calcium to influence the resting concentration, and that this effect is reversible by haemodialysis.

Bleeding due to impaired primary haemostasis is common in uraemia. However, thrombo-embolic episodes are also a clinical problem in dialysis patients. Platelet reactivity to shear stress (haemostasis, H1 and H2), exposure to collagen fibre (thrombus growth) and coagulation of flowing blood (clotting time, CT1 and CT2) were measured in non-anticoagulated blood samples taken immediately before and 18-24 h after haemodialysis (n = 26) and from patients maintained on continuous ambulatory peritoneal dialysis (CAPD, n = 30). H1 (p < 0.001), H2 (p < 0.01), percent thrombus growth rate (p < 0.03), CT1 (p < 0.01 and CT2 (p < 0.05) were restored towards normal after haemodialysis. Results obtained in the CAPD patients demonstrated that the mean values for formation of the haemostatic plug lay between the pre- and posthaemodialysis values; however, CT1 (p < 0.01) and CT2 (p < 0.05) were prolonged in CAPD compared with values after haemodialysis. These data, which indicate platelet function from non-anticoagulated blood and coagulation under flow conditions, (1) confirm that there is impaired haemostasis in uraemia; (2) demonstrate an improvement in haemostasis after haemodialysis; (3) show that peritoneal dialysis results in a haemostatic profile which falls between the pre- and posthaemodialysis pattern, and (4) show that neither dialysis modality returns haemostasis to normal.

We identified twenty patients maintained on continuous ambulatory peritoneal dialysis who suffered repeated episodes of peritonitis caused by coagulase-negative staphylococci. We documented hand and exist-site coagulase-negative staphylococcus-associated peritonitis over a total period of 32 months, and compared hand and exit-site strains with strains isolated from dialysate fluid using three typing methods: biotyping using the API Staph kit plus antibiograms, immunoblotting using sera raised in rabbits to three standard strains of coagulase-negative staphylococci, and 35S-methionine-labelled coagulase-negative staphylococcal profiles separated on sodium dodecylsulphate polyacrylamide gel electrophoresis and visualised by autoradiography (radioPAGE). In 5 of 84 episodes, strains isolated from skin were indistinguishable by all three typing methods from the dialysate strain. In a further two episodes, hand or exit-site isolates were indistinguishable by all three typing methods from the dialysate strain isolated in the subsequent, but not the same, episode. Thus in the majority of episodes, no inference of hand or exit-site origin of dialysate infection could be drawn.

We have described 4 patients with chronic renal failure receiving regular haemodialysis treatment who underwent total parathyroidectomy with autotransplantation of parathyroid fragments into the forearm musculature for hypercalcaemic hyperparathyroidism. In all, there was an immediate and profound fall in plasma calcium levels. Hypercalcaemia recurred 1-5 years post-operatively and was resistant to resection of the autograft. In 3 cases, thallium-technetium subtraction scanning and multiple venous sampling for estimation of parathyroid hormone levels suggested multiple sites of hypersecretion of parathyroid hormone in the neck. In 1 case, these investigations revealed a mediastinal adenoma which was successfully removed. These cases reinforce previous suggestions that total parathyroidectomy is frequently incomplete and undermine the procedure of total parathyroidectomy with autotransplantation in patients with persisting uraemia.

1,25(OH) 2 D 3 administration in moderate renal failure: A prospective double blind trial. This study represents the first randomized prospective, double-blind, placebo-controlled trial of the efficacy of 1,25(OH) 2 D 3 on bone histology and serum biochemistry in patients with mild to moderate renal failure. Sixteen patients with chronic renal impairment (creatinine clearance 20 to 59 ml per min) received either 1,25(OH) 2 D 3 , at a dose of 0.25 to 0.5 µg daily (eight patients), or placebo. Transiliac crest bone biopsies were performed before entrance into the study and after 12 months of experimental observation. None of the patients were symptomatic or had radiological evidence of bone disease. Of the thirteen patients who completed the study, initial serum 1,25(OH) 2 D levels were low in seven patients and parathyroid hormone levels were elevated in seven patients. Bone histology was abnormal in all patients. 1,25(OH) 2 D 3 treatment was associated with a significant fall in serum phosphorus and alkaline phosphatase concentrations as well as with histological evidence of an amelioration of hyperparathyroid changes. In contrast to previous reports, no deterioration of renal function attributable to the treatment occurred, perhaps because a modest dose of 1,25(OH) 2 D 3 was employed combined with meticulous monitoring. Further investigation is required to determine whether alternative therapeutic strategies (smaller doses or intermittent therapy) may avoid the potential for suppressing bone turnover to abnormally low levels in the long term.

Fibrinogen/fibrin degradation products (FDP) have been measured in serum by radioimmunoassay for fragment E (FgE), one of the terminal fragments in plasmic digestion of fibrinogen, and the results compared with those determined by both a tanned red cell haemagglutination inhibiton immunoassay (TRCHII) and a latex particle agglutination inhibition immunoassay. The detection limit of the FgE assay was 0.8 ng/ml, that of TRCHII was 625 ng/ml and the latex particle agglunitaion inhibition immunoassay was 10 mug/ml. All the samples measured had detectable levels of FDP with the FgE assay, whereas only 88% were measurable with the TRCHII and 2% by the latex particle agglutination inhibition immunoassay. A comparison of those samples giving a positive result with both the TRCHII and FgE assay showed overall agreement between the results of the two types of assay, but there was considerable scatter of FgE levels at each point of the TRCHII. The major advantages of the radioimmunoassay system are greater sensitivity, specificity and reproducibility.

Summary. Twenty-two patients with accelerated hypertension and varying degrees of renal involvement have been studied in order to assess the significance of microangiopathic haemolytic anaemia (MAHA) and the possible pathogenic role of intravascular fibrin deposition in this condition. Vascular damage was assessed by retinal photography including fluorescein angiography. Haematological investigations including examination of peripheral films and assessment of red cell fragmentation were carried out. Fibrinogen catabolism was measured using radio-iodine labelled fibrinogen. No correlation between the degree of vascular damage in the retinal vessels and the blood pressure, degree of red cell fragmentation or evidence of renal damage was found. There was a significant increase in red cell fragmentation when the creatinine clearance was 20 ml/min or less. Fibrinogen derivatives were demonstrated in the serum in the minority and in the urine of the majority of those patients with MAHA. Fibrinogen catabolism was normal in all cases. The significance of microangiopathic haemolytic anaemia in accelerated hypertension is discussed. It is suggested from these data that the red cell fragmentation occurs predominantly within the kidney and that there is no evidence that fibrinogen deposition plays an important role in red cell damage, or that it is an important pathogenic factor in producing accelerated hypertension.

Summary. Fibrinogen catabolism has been studied in six patients with microangiopathic haemolytic anaemia, three patients with fragmentary haemolytic anaemia following the insertion of valve prostheses into the heart and ten control patients. Increased rates of catabolism of 131 I-fibrinogen were found in the patients with microangiopathic haemolytic anaemia. Evidence of enhanced fibrinolysis was not present. This finding suggests that intravascular coagulation is a feature of some cases of microangiopathic haemolytic anaemia and supports the hypothesis that the interaction of red cells with fibrin may result in the characteristic morphological appearances in these cases.

Summary. Twelve patients are described who developed well-marked micro-angiopathic haemolytic anaemia in association with metastatic carcinoma. The tumours originated in the stomach in six cases, in the breast in two cases, in the lung in one case and the origin was uncertain in three cases. All 11 tumours studied were found to be mucin-secreting adenocarcinomas. Ten out of the 12 patients were thrombocytopenic. Fibrinogen metabolism was studied in four patients and in each patient the catabolism of fibrinogen was found to be greatly increased despite normal or near normal plasma fibrinogen levels and an absence of overt fibrinolysis. Fibrin degradation products were demonstrated in the serum of five out of six patients. Hyaline thrombi were seen in the small blood vessels in the kidneys and suprarenals in one patient and in the myocardium in two patients, while changes suggestive of organized thrombi were present in the interlobular arteries of the kidneys in three patients. It is thought likely that the microangiopathic haemolytic anaemia develops secondarily to intravascular coagulation brought about by thromboplastins derived from mucin-forming tumour cells which have entered blood vessels, and that contact between circulating red cells and tumour emboli within blood vessels may be an additional cause of red-cell damage.

1. Tamm—Horsfall (T—H) glycoprotein has been measured by a specific radioimmunoassay method in the urine of patients with chronic renal failure, cadmium nephropathy and Lignac—Fanconi syndrome, and in renal and bladder calculi. 2. Total T—H glycoprotein excretion/24 h was markedly reduced in patients with chronic renal failure compared with normals. A highly significant correlation was observed between T—H excretion rate and creatinine clearance corrected for surface area, in both normals and patients with renal impairment. However, the mean T—H excretion per functioning nephron unit did not differ significantly in patients with renal failure compared with normals. 3. Total T—H excretion/24 h was in the normal range in patients with cadmium nephropathy despite reduced glomerular filtration rates, owing to a highly significant increase in T—H excretion per functioning nephron unit. Similar findings were obtained in a group of children with Lignac—Fanconi syndrome whose T—H excretion per functioning nephron unit was much higher than that of normal children in the same age range. This indicates an increased T—H glycoprotein excretion per functioning nephron unit in both these conditions. 4. T—H glycoprotein content of bladder and renal calculi ranged from 0002 to 5.07 mg/g of calculus. There was no correlation between T—H glycoprotein content and either the total protein content or the qualitative inorganic composition of the stones.

A case of autoimmune haemolytic anaemia is described in which recovery, with disappearance of antibody, followed splenectomy and removal of an ovarian ;dermoid' cyst. A causal relationship between removal of the ovarian tumour and recovery is strongly suggested and the possible pathogenesis discussed. Fourteen previously recorded cases of this association are reviewed.

Effects of oxygen breathing and erythropoietin on hypoxic vasodilation in uremic anemia. Loss of hypoxic vasodilation has been proposed as a causative factor in the development of hypertension in dialysis patients treated with recombinant human erythropoietin (rHuEPO). Venous occlusion plethysmography was therefore performed on 22 dialysis patients (aged 23 to 71 years, dialysis duration 6 to 260 months, 8 males) before and after correction of anemia with rHuEPO, 50 U/kg 3×/week (Hb: 7.4 ± 0.3 vs. 10.8 ± 0.3 g/dl, P < 0.0001). Hypertension (> 15mm Hg rise in mean BP) occurred in 11 patients. The study was performed while breathing room air and repeated after breathing 60% O2 for 10 to 12 minutes. Before rHuEPO therapy, total blood O2 content increased from 10.01 ± 0.39 to 10.32 ± 0.29ml O2/100ml blood with breathing 60% 02 (P < 0.01). After correction of anemia it was 14.65 ± 0.40mlO2/100ml blood on room air (P < 0.001). There was a significant decrease in forearm blood flow (7.9 ± 0.5 vs. 6.5 ± 0.6ml/min/100ml tissue, P < 0.05) and increase in forearm vascular resistance (12.8 ± 0.1 vs. 16.8 ± 0.2mm Hg/ml/min/100ml tissue, P < 0.05) with O2 breathing prior to rHuEPO therapy in the blood pressure responders, but no change in these parameters in the group in which blood pressure remained unchanged. When all patients were studied on room air, forearm vascular resistance rose significantly after correction of anemia (13.0 ± 0.8 vs. 16.3 ± 0.8mm Hg/ml/min/100ml tissue, P < 0.05), compared with that prior to rHuEPO therapy. However, no difference in this increase was detected between blood pressure responders and non-responders. In conclusion, forearm vascular resistance increases in uremic anemia in response to increased delivery of O2, suggesting the existence of significant hypoxic vasodilation. The reversal of hypoxic vasodilation achieved by increased pO2 is greater in patients in whom blood pressure increases during correction of anemia. The enhanced vascular reactivity to reversal of low blood oxygen content present in these patients may partly account for the development of hypertension.

Summary The catabolism of purified human 125I labelled IgG has been studied in patients with chronic renal failure, both nephrectomised and non-nephrectomised, on intermittent haemodialysis. In all patients the T1/2 of IgG was the same as in normal controls, and using chromatographic separation on Sephadex G200, there was no evidence of alteration of molecular size as a result of dialysis. The results do not support the notion that the kidney is an important site of IgG catabolism in humans.

Serial abdominal computed tomography (CT) scans have been performed in 15 patients with biopsy-proven idiopathic retroperitoneal fibrosis. Twelve patients had abdominal CT both before diagnosis and at a variable time later. All 12 patients showed a decrease in the size of the retroperitoneal mass at follow-up, although two had not been treated with steroids. The remaining three patients who had abdominal CT at some stage after diagnosis all showed a small residual retroperitoneal mass. Based on the findings, guidelines for the use of CT in the follow-up of retroperitoneal fibrosis are discussed.

Summary— Eighty-eight urinary tract stone formers (74 men) with idiopathic hypercalciuria were treated by dietary calcium restriction alone. Short-term control of hypercalciuria was achieved in only 27 patients and all but 12 eventually escaped control. Failure of control was twice as likely in patients with severe hypercalciuria. Almost all patients lived in a hard water area. In such areas at least, attempts to control hypercalciuria by diet alone are likely to fail and early introduction of additional treatment is advisable. In most severe hypercalciurics, such treatment should be introduced from the start.

An X-linked dominant mutation (gyro, gene symbol Gy) in the laboratory mouse causes hypophosphatemia, rickets/osteomalacia, circling behavior, inner ear abnormalities, and sterility in males and a milder phenotype in females. Gy maps closely (crossover value 0.4-0.8%) to another X-linked gene (Hyp) that also causes hypophosphatemia in the mouse. Gy and Hyp genes have similar quantitative expression in serum phosphorus values, renal excretion of phosphate, and impairment of Na+/phosphate cotransport by renal brush-border membrane vesicles. These findings indicate that independent translation products of two X-linked genes serve phosphate transport in mouse kidney and thereby control phosphate content of extracellular fluid. The Gy translation product, unlike the Hyp product, is also expressed in the inner ear. These findings have implications for our understanding of the human counterpart known as "X-linked hypophosphatemia."

In the period 1970–1983, 27 patients with end stage renal failure underwent neck exploration for hyperparathyroidism. In 1977 the operative policy changed from subtotal parathyroidectomy to total parathyroidectomy and autotransplantation. Eight patients underwent subtotal parathyroidectomy while fifteen patients underwent total parathyroidectomy and autotransplantation. All were cured of their symptoms and hypercalcaemia was resolved. There was no significant difference in the requirement for postoperative calcium and vitamin D supplements between the two groups. Recurrent hypercalcaemia developed in one patient who had undergone total parathyroidectomy and autotransplantation. Resolution followed removal of approximately half the transplant. There were four deviations from the operative policy.

Summary Levels of fibrin/fibrinogen degradation products have been measured by a sensitive and specific radioimmunoassay in pregnancies associated with pre-eclampsia or essential hypertension. The incidence of elevated levels was low (2.4 per cent) in mild and moderate cases, and rather higher (30 per cent) in severe cases. In no patients were the levels consistently elevated prior to the onset of clinical signs.

Sixty patients with idiopathic retroperitoneal fibrosis presenting between 1965 and 1984 are reviewed. Their mean age at presentation was 56 years and the male:female ratio was 3:1. The commonest presenting symptoms were flank and abdominal pain, weight loss, nausea and polyuria. Physical examination was usually normal, expect for the presence of hypertension. Anaemia and elevation of erythrocyte sedimentation rate were usually present. Proteinuria was found in less than a third of patients at presentation and significant bacteriuria was uncommon. The correct diagnosis was made or suspected in very few patients before referral. The cumulative actuarial survival rate was 86% at 1 year and 78% at 2 years. Seventeen patients died; they were significantly older and more uraemic at the time of referral than those who survived. A few patients did well with either corticosteroid therapy or ureterolysis alone. In the majority, both operation and steroid treatment were necessary. In bilateral obstruction with residual function in both kidneys, bilateral ureterolysis proved superior to unilateral operation (each followed by steroid therapy) in conserving renal function. Operation alone or steroid therapy alone should be considered in cases where steroids or surgery respectively present particular hazards. The less traumatic unilateral operation should be considered in poor risk patients and in those whose renal function is absent on one side. In many survivors, disease activity has persisted for many years. Life-long follow-up is recommended.

Effect of dialysate composition on intercompartmental fluid shift. Effect of dialysate composition on intercompartmental fluid shift and hemodynamics was studied in 12 patients during 1.5 or 2 hours of hemodialysis without net ultrafiltration, using high (H;Na 154 mmol/liter), normal (N;Na 140 mmol/liter) or low (L:Na 126 mmol/liter) concentration dialysate. H dialysate was associated with a small (0.9%) increase in blood volume, a larger increase in plasma volume and a decrease in erythrocyte volume. L dialysate resulted in a 2.3% decrease in blood volume, a larger decrease in plasma volume and an increase in erythrocyte volume. N dialysate gave results which were intermediately between the other two dialysis conditions. There was no difference in the post-dialysis mean arterial pressure between the groups, although heart rate increased more during H dialysis than during the other two conditions. Change in blood and erythrocyte volume correlated significantly with change in plasma Na concentration and osmolality, but not with change in plasma urea concentration. We conclude that dialysate composition affects the movement of water into and out of the plasma and erythrocytes in a manner that can be accounted for by altered plasma concentrations of osmotically active substances.

In a patient receiving regular dialysis prolonged hypophosphataemia due to aluminium hydroxide therapy resulted in osteomalacia and severe proximal myopathy. Both osteomalacia and myopathy responded to correction of hypophosphataemia without vitamin D therapy.

Summary Levels of fibrin/fibrinogen degradation products have been measured by aspecific and sensitive radioimmunoassay for degradation fragment E (FgE) in pregnant patients. Maternal FgE levels rose from the 16th week reaching a plateau at the 36th week in normal pregnancy. There was no correlation between maternal FgE levels and maternal age, parity or the occurrence of perinatal asphyxia. A minority of patients (5 percent) with evidence of intrauterine growth retardation showed prolonged elevation of FgE levels.

Total white cell, neutrophil, and lymphocyte counts were compared in patients with chronic renal failure treated successively by conservative means (low-protein diet), regular haemodialysis, and renal allotransplantation. The lowest total white cell and neutrophil counts and the highest lymphocyte counts were found in patients on regular haemodialysis. A rapid fall in neutrophil count during the first half-hour of dialysis and a more gradual fall between the first and sixth hours were observed. Adherence of neutrophils and mononuclear cells to the cuprophane (PT 150) dialysis membrane has been shown.

1. A cation-exchange-chromatographic method for the determination of methylguanidine in serum is described. 2. In ten normal subjects, the mean serum methylguanidine concentration was 0.055 (SE 0.019) mg/100 ml and in ten uraemic patients it was 0.175 (SE 0.038) mg/100 ml. This difference is significant (P < 0.02). 3. Recent claims that methylguanidine is present in uraemic serum in much higher concentrations are shown to be due to artifactual conversion of creatinine when methods involving charcoal chromatography are employed. 4. The results of intoxication experiments, in which blood concentrations of methylguanidine similar to those found by charcoal-chromatographic methods have been reproduced, must be interpreted with caution.

The response of three children and four adult women with microangiopathic haemolytic anaemia to treatment with heparin is described. The one child and three adults treated within 10 days of the onset of the illness recovered rapidly and completely from their anaemia, thrombocytopenia and uraemia. The two children and one adult treated between 18 and 31 days after the onset of the illness responded less well. The two children who were given small doses of heparin died from complications of the renal microangiopathy despite improvement in the haemolysis and thrombocytopenia. The adult woman made a slow and partial recovery; the haemolysis and thrombocytopenia improved, but renal function did not return to normal. The importance of recognizing and treating the low grade intravascular coagulation which may accompany microangiopathic haemolytic anaemia is stressed. It is suggested that the variable response to treatment with heparin of patients with microangiopathic haemolytic anaemia observed by ourselves and others may be due to relative roles of intravascular coagulation and primary vascular disease in the pathogenesis of the microangiopathy, and to the development of irreversible vascular damage if treatment is delayed.