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This study examined the effect of the angiotensin converting enzyme (ACE) inhibitor, enalaprilat, on mesangial cell (MC) DNA synthesis induced by H2O2, IL-6 and PDGF. MC were incubated with enalaprilat (2.5-100 mumol/l) alone and together with combinations of H2O2 (3 daily pulses of 10(-6) mol/l), IL-6 (5 ng/ml) and PDGF (10 ng/ml). DNA synthesis was assessed after 72 h using [3H]thymidine (3H-TdR) incorporation. Enalaprilat alone had no effect on MC DNA synthesis. Stimulation of MC by H2O2, PDGF and IL-6 alone resulted in increases in 3H-TdR of 4936.6 +/- 1147.5, 5640.5 +/- 1537.6 and 4413.5 +/- 998.4 cpm, respectively (P < 0.05 above control). Only 2.5 mumol/l enalaprilat effected a significant reduction in IL-6 and PDGF-induced DNA synthesis. Incubation of MC with H2O2 + PDGF or H2O2 + IL-6 resulted in increases of 3H-TdR of 6471.9 +/- 1785.1 and 5507.2 +/- 1270 cpm, respectively (P < 0.05 above control). Addition of enalaprilat with either H2O2 + PDGF or H2O2 + IL-6 effected significant reductions in DNA synthesis over the range 2.5-100 mumol/l. These data demonstrate that ACE inhibitors modulate MC DNA synthesis induced by reactive oxygen species.

This study indirectly examined the role of prostanoids (PG) in mediating rat mesangial cell (MC) DNA synthesis induced by hydrogen peroxide (H2O2), interleukin 6 (IL-6), and platelet-derived growth factor (PDGF). MC were exposed to three daily pulses of 10(-6) mol/l H2O2 alone or in combination with IL-6 (5 ng/ml) or PDGF (10 ng/ml). In order to examine (indirectly) the role of PG in mediating changes in MC DNA synthesis, indomethacin (1.5 x 10(-5) mol/l) or the thromboxane A2 synthetase inhibitor Dazmegrel (10(-5) mol/l) was added to the medium and DNA synthesis assessed after 72 h using 3H-thymidine incorporation (3H-TdR). Stimulation of MC by H2O2 alone resulted in an increase in 3H-TdR of 34.7 +/- 5.5% (p < 0.01). H2O2 enhanced the mitogenic effects of IL-6 and PDGF, 3H-TdR increasing by 52 +/- 12.1% (p < 0.01) and 100 +/- 21% (p < 0.001), respectively. Indomethacin suppressed the DNA synthesis induced by H2O2 alone, 3H-TdR decreasing by 33 +/- 12% (p < 0.05). Indomethacin also reduced the mitogenic response to H2O2 plus IL-6 and H2O2 plus PDGF by 91 +/- 17 and 97 +/- 12%, respectively (p < 0.05). Dazmegrel reduced 3H-TdR when MC were exposed to H2O2 alone by 31.8 +/- 16% (p < 0.05) and when combined with IL-6 or PDGF by 80 +/- 26 and 120 +/- 13%, respectively (p < 0.05). These data suggest that the pathways through which H2O2-induced growth of MC is mediated appear, at least in part, to involve PG, particularly thromboxane A2.

1. This study examined the influence of H2O2, interleukin-6 and platelet-derived growth factor on the proliferation of rat mesangial cells. Mesangial cells were exposed to either a single pulse or three daily pulses of H2O2 (10(-8)-10(-4) mol/l), alone or in combination with interleukin-6 (5 ng/ml) and/or platelet-derived growth factor (10 ng/ml). Proliferation was assessed after 24 h and 72 h of incubation using [3H]thymidine incorporation and cell counts. 2. Although one pulse of H2O2 had no significant effect on mesangial cell proliferation, three daily pulses of 10(-6) mol/l H2O2 resulted in a significant increase in [3H]thymidine incorporation of 31 (52.6, 10.3)% (median and 75th-25th interquartile range) (P < 0.001). Both interleukin-6 and platelet-derived growth factor were also mitogenic to mesangial cells, [3H]thymidine incorporation increasing by 19 (36.7, -6.7)% (P < 0.05) and 53.5 (107, 21.9)% (P < 0.001), respectively. The mitogenic effect of interleukin-6 was enhanced by 10(-6) mol/l H2O2 [49.9 (77.7, 12.3)%] (P < 0.01), whereas the addition of 10(-6) mol/l H2O2 to platelet-derived growth factor resulted in a summated increase in [3H]thymidine incorporation of 82.7 (113, 57.4)% (P < 0.001). Incubation with all three substances simultaneously resulted in down-regulation of growth compared with H2O2 plus platelet-derived growth factor by 55.4 (77.7, 10.3)% (P < 0.05). 3. These findings suggest that reactive oxygen species may play a major role in determining the mesangial cell proliferation that occurs in certain forms of glomerulonephritis, acting either alone or in combination with other growth factors.

We describe studies in whole kidney, cortical and medullary homogenates and, glomerular cells in culture to determine the relative levels of expression of alpha (Ya, Yc, Yk), mu (Yb1/Yb2), pi (Yf) glutathione S-transferases (GST) and CuZn superoxide dismutase (CuZn SOD) in different regions of the nephron. Immunoblotting and immunohistochemistry were used to demonstrate relatively weak expression of alpha, mu GST and, CuZn SOD in the glomerulus compared to that in particularly distal tubules. Whilst expression of Ya was found within glomerular cells, Yc, Yk and Yf were not detected. Immunofluorescence showed that Ya and Yb1/Yb2 but not Yf were expressed in cultured epithelial and mesangial cells studied between passages 1 and 3. While Ya was distributed in cytosol, Yb1/Yb2 was primarily located in nuclei.

1. This study was designed to investigate whether the angiotensin converting enzyme (ACE) inhibitors, captopril, enalapril and fosinopril have a dose-dependent effect on the production of prostaglandin E2 (PGE2), prostaglandin I2 (prostacyclin, PGI2) and thromboxane A2 (TxA2) by glomeruli isolated from normotensive Wistar-Kyoto rats. 2. Measurements of glomerular prostanoid production were made under basal conditions and in the presence of excess exogenous arachidonic acid. 3. All three ACE inhibitors demonstrated dose-dependent effects upon glomerular prostanoid production which varied with the individual ACE inhibitor. 4. Enalapril induced a dose-dependent increase in the ratio of (PGE2 + PGI2)/TxA2, from 2.17 +/- 0.20 to 5.35 +/- 0.84 and to 10.0 +/- 1.16 with the low and high doses of enalapril respectively. In contrast, the high dose of captopril tended to reduce the ratio when compared to the low dose. 5. The results obtained in this study suggest that although all three ACE inhibitors appear to induce prostacyclin synthetase and/or modulate phospholipase A2 (PLA2) activity, these effects differ with the ACE inhibitor studied and the dose employed. 6. This study has demonstrated dose-dependent effects of three ACE inhibitors on glomerular prostanoid production which may be significant in modulating glomerular haemodynamics and growth characteristics of glomerular cells.

1. The effect of H2O2 (4.7 x 10(-9) -4.7 x 10(-3) M) on prostanoid production by isolated glomeruli from normotensive (WKY) and, spontaneously hypertensive rats (SHR) has been studied. 2. Oxidant stress significantly increased synthesis of prostaglandin E2 (PGE2), I2 (PGI2) and thromboxane A2 (TxA2) by glomeruli from both strains whereas the ratio (PGE2 + PGI2)/TxA2 increased in only SHR. 3. Pre-incubation of glomeruli with the angiotensin converting enzyme inhibitors captopril or lisinopril, had virtually no effect on H2O2-induced synthesis of individual prostanoids nor on the ratio (PGE2 + PGI2)/TxA2 by glomeruli from either WKY or SHR. 4. The findings suggest that H2O2-induced changes in glomerular function may be mediated, in part, by PGs but fail to support the suggestion that the ability of ACEI to protect glomeruli from H2O2-induced damage is determined by PGs.

1. The effect of oestradiol alone and in combination with indomethacin on blood pressure, erythrocyte cation concentration and Na(+)-K+ flux has been studied in adult female normotensive and spontaneously hypertensive rats. 2. Oestradiol alone resulted in a significant decrease in blood pressure in spontaneously hypertensive rats (from 165.3 +/- 3.9 to 146.4 +/- 2.7 mmHg, P less than 0.001), whereas it induced a significant increase in normotensive rats (from 111.8 +/- 1.8 to 124.1 +/- 3.6 mmHg, P less than 0.001). When indomethacin and oestradiol were administered simultaneously or when indomethacin was given alone, no change in blood pressure occurred in spontaneously hypertensive rats (158.6 +/- 6.9 and 159.8 +/- 6.2 mmHg, respectively). 3. The fall in blood pressure induced by oestradiol in spontaneously hypertensive rats was associated with significant reductions in erythrocyte K+ concentration (from 127.4 +/- 1.2 to 116.9 +/- 1.7 mmol/l of cells, P less than 0.001), in erythrocyte Na+ concentration (from 14.3 +/- 0.8 to 13.0 +/- 0.6 mmol/l of cells, P less than 0.02), in ouabain-sensitive erythrocyte Na+ flux (from 17.8 +/- 0.3 to 16.0 +/- 0.4 mmol h-1 (l of cells)-1, P less than 0.01) and in ouabain-sensitive erythrocyte K+ flux (from 11.4 +/- 0.2 to 10.4 +/- 0.2 mmol h-1 (l of cells)-1, P less than 0.01). No change in blood pressure, erythrocyte cation concentration or Na(+)-K+ flux occurred when oestradiol and indomethacin were given together or when indomethacin was administered alone.(ABSTRACT TRUNCATED AT 250 WORDS)

1. This study was designed to examine the production of certain eicosanoids (prostaglandin E2), prostacyclin (as 6-keto-prostaglandin F1 alpha) and thromboxane A2 (as thromboxane B2) by glomeruli isolated from normotensive Wistar-Kyoto and spontaneously hypertensive rats both before and after the administration of one of three angiotensin-converting enzyme inhibitors, captopril, enalapril or fosinopril, for 10 days. 2. Measurements of glomerular eicosanoid production were made under basal conditions and in the presence of excess exogenous arachidonic acid. 3. The production of prostaglandin E2, 6-keto-prostaglandin F1 alpha and thromboxane B2 was greater by glomeruli from untreated spontaneous hypertensive rats (prostaglandin E2 2.24 +/- 0.41, 6-keto-prostaglandin F1 alpha 1.20 +/- 0.13 and thromboxane B2 2.75 +/- 0.43 ng 10 min-1 mg-1 of protein) than by those from Wistar-Kyoto rats (prostaglandin E2 1.41 +/- 0.28, 6-keto-prostaglandin F1 alpha 0.98 +/- 0.11 and thromboxane B2 1.29 +/- 0.24 ng 10 min-1 mg-1 of protein) under basal conditions. However, these differences only achieved statistical significance for thromboxane B2 (P less than 0.01). Similar strain-related differences were noted in the presence of arachidonic acid. 4. The ratio of glomerular (prostaglandin E2 + prostacyclin)/thromboxane A2 production was significantly lower in spontaneously hypertensive rats than in their normotensive counterparts under basal conditions with values of 1.3 +/- 0.18 and 2.2 +/- 0.20, respectively (P less than 0.01). 5. Angiotensin-converting enzyme inhibitors induced significant changes in the glomerular production of some eicosanoids, which differed both between strains and with the nature of the inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Our belief in a non-operative approach to the management of RPF hinges on the differential diagnosis; the closer the approach to the certainty in establishing the diagnosis, the less is the risk of error in medical treatment. Careful history taking and intelligent use of the available range of investigations should allow near certainty in diagnostic accuracy and thus the progression to non-operative management in most patients. The cause of RPF remains obscure, further research into the possibility of an auto-immune reaction, perhaps a response to some factor introduced in the latter half of this century would seem to offer most prospect of success.

Normotensive women with a previous history of oestrogen-associated hypertension were found to have raised platelet factor 3 (PF3) availability, raised triglycerides and pre-beta-lipoprotein and impaired fibrinolytic activity and capacity, but were shown to have normal platelet lifespan and renal platelet localization. The significance of these abnormalities in relation to the development of hypertension and to the intrarenal vascular disease found in these patients is discussed.

Angiographic and histological studies of the intrarenal circulation have been undertaken in 20 patients following complicated pregnancies: 12 patients had had hypertension of pregnancy (group 1); 7 acute renal failure due to either ante- or post-partum haemorrhage and 1 patient post-partum renal failure (group 2). 3 months after delivery all patients had angiographic evidence of structural and functional abnormalities involving intrarenal blood vessels and cortical blood flow. The severity of the structural changes was related to the degree of microangiopathic haemolytic anaemia noted in the acute obstetric complication but not to the height of the blood pressure at this stage. Histological abnormalities of the cortical blood vessels were minimal. At the time of the renal angiogram and biopsy, 3 of the 12 group 1 patients were hypertensive and 3 had impaired renal function, compared with 5 and 1, respectively, in the 8 group 2 patients. Although during the follow-up period (mean 5 years) no further deterioration in renal function in either group has been observed, hypertension developed in 50% of the group 1 patients compared with only 1 of the patients in group 2. The relationship between the late onset of hypertension and the intrarenal vascular and haemodynamic abnormalities is discussed.

The histological appearances of the proximal and peripheral intrarenal arteries and renal cortex have been examined in 3 patients who underwent nephrectomy for intractable pain associated with the loin-pain-haematuria syndrome. Marked 'atherosclerotic' changes were noted to involve segmental, lobar, interlobar and arcuate arteries with evidence in one kidney of early microaneurysmal formation. These lesions of the more proximal intrarenal arteries were associated with occlusive lesions of the interlobular arteries, areas of cortical ischaemia and cortical infarcts consistent with the changes resulting from microemboli. The histological appearances correlated well with previously described angiographic findings.

The effect of oestrone acetate (in total doses of 5 and 10 mg) on systemic and renal haemodynamics and the renin-angiotensin system has been studied in adult female rats. The administration of 10 mg of oestrogen resulted in a significant fall in renal blood flow associated with significant rises in both renal vascular resistance and mean arterial pressure. No changes were noted in cardiac output or total peripheral resistance at either dose. Whilst the higher dose of oestrogen induced a significant increase in plasma renin activity, no change was noted in animals receiving 5 mg of oestrogen. Both regimens caused significant reductions in plasma and intrarenal renin concentrations. Although renal blood flow correlated with plasma renin activity in animals with a normal renal blood flow, no such correlation was noted in animals with oestrogen-induced reductions in renal blood flow. The present study demonstrates that oestrogen-induced reductions in renal blood flow result from a rise in intrarenal vascular resistance which cannot be accounted for by simultaneous changes in either plasma renin activity or renal renin concentration.

Thyroid function has been studied in eleven patients with the 'idiopathic oedema syndrome'. Six patients have been shown to have subclinical hypothyroidism associated with the presence of thyroid antibodies. All responded to treatment with sodium thyroxine. Five patients had normal thyroid function, absence of thyroid antibodies and failed to respond to treatment with sodium thyroxine.

1. Platelet factor 3, platelet survival, renal platelet localization and fibrinolytic activity have been studied in normotensive subjects with a previous history of pregnancy-associated hypertension. Studies were carried out up to 6 years after the complicated pregnancy. 2. Renal platelet localization was found to be significantly increased despite normal platelet survival and platelet factor 3 availability. Significant impairment of both resting and post-venous-occlusion fibrinolytic activity was also demonstrable. 3. The significance of these findings in relation to mediation of progressive intrarenal vascular disease is discussed.

26 patients with systemic lupus erythematosus (SLE) induced by treatment with the antihypertensive drug hydralazine were investigated to determine if predisposition to the toxic effect was associated with an HLA-DR antigen. 25 of the 26 patients were slow acetylators. The group was compared with three others (1) 113 healthy subjects, untested for acetylator phenotype, (2) 16 slow-acetylator hypertensive patients treated with hydralazine for more than a year without developing SLE, and (3) 20 patients with idiopathic SLE. The frequency of HLA-DR4 (73%) was significantly higher in the group with hydralazine-induced SLE than in the other groups (respectively 33%, 25%, and 25%). The ratio of women to men affected was 4:1. If the slow acetylators treated with hydralazine were analysed as one group, it was observed that all women with DR4 developed hydralazine-induced SLE; the only men to do so were those with DR2 who were receiving 200 mg hydralazine per day. These observations have led us to suggest guide lines for hydralazine therapy and point to a striking association between an HLA-DR antigen and an adverse reaction to a therapeutic agent. It was also noted that the distribution of DR antigens in the hydralazine-SLE patients was significantly different from that in the group with idiopathic SLE. This supports the view that the syndromes are separate entities.

Two patients are described who developed subarachnoid haemorrhage during pregnancy and the puerperium. In both patients there was clinical, haematological, histological, and renal angiographic evidence of the intravascular coagulation syndrome. No source of intracranial bleeding was demonstrated by bilateral carotid angiography in either patient. We suggest that the subarachnoid haemorrhage was a result of the intravascular coagulation syndrome in both patients.

Serial measurements were made of the cerebrospinal fluid and plasma amino-acid concentrations in 12 patients with purulent meningitis. Marked increases in the concentrations of most CSF amino-acids were found, possibly caused by altered transport mechanisms in the inflamed meninges and choroid plexuses.

Serial measurements have been made of the cerebrospinal fluid and plasma amino acid concentrations in 11 patients with viral meningitis and in four with tuberculous meningitis. A small increase in the concentrations of a few amino acids in cerebrospinal fluid has been found in a viral meningitis in contrast to a marked increase in most amino acids in tuberculous meningitis. The findings are compared with those found in patients with purulent meningitis and the possible causes and the diagnostic significance of these findings are discussed.

The effect of oestrogen-containing compounds on platelet factor 3, platelet life span, renal platelet localization and the fibrinolytic activity of forearm venous blood has been studied in eleven women with the renal vascular abnormalities of the loin pain and haematuria syndrome. The results were compared with those obtained in twenty-nine healthy female volunteer subjects. 2. Platelet factor 3 (PF3) availability was found to be increased in patients with the loin pain and haematuria syndrome during normal menstrual cycles. Oestrogens produced an increase in PF3 availability in both patients and control subjects. 3. Platelet life span was shortened and the index of renal platelet localization increased when patients with the loin pain and haematuria syndrome received oestrogens. No change in platelet kinetics was found in the healthy control subjects receiving oestrogens. 4. The fibrinolytic activity of forearm venous blood, both at rest and after venous occlusion, was increased in the healthy control subjects in response to oestrogens. No such response was seen in the patients with the loin pain and haematuria syndrome. 5. It is suggested that the change in platelet function may be causally related to the intrarenal vascular abnormalities. 6. The possible role of oestrogens in causing these disturbances or unmasking pre-existing abnormalities of platelet function or fibrinolysis is discussed.

Nine patients who developed reversible hypertension and/or evidence of impaired renal function whilst taking an oestrogen-progestogen-containing compound have been investigated. Serial haematological and biochemical studies have been carried out on each patient in association with selective renal angiography and renal biopsies. Abnormalities of the peripheral renal vessels have been demonstrated in all patients and a close correlation between the histological and angiographic appearances noted. The presence of microthrombi involving glomerular capillaries or intrarenal arterioles was invariably accompanied by evidence of micro-angiopathic haemolytic anaemia along with stasis of contrast medium in the intra-renal vascular circulation. Although the three different groups of patients studied tended to show their own particular intra-renal angiographic patterns, the definitive diagnosis depended on the haematological and histoligical findings. In the majority of patients, withdrawal of the oestrogen-progestogen-containing compound resulted in clinical improvement.

A high incidence of raised levels of circulating immune complexes has found in a group of patients with idiopathic vasculitis. Serial measurements in 8 patients with systemic vasculitis showed a good correlation between clinical status and circulating immune complex levels. Some correlation existed between the constituents of circulating and tissue-bound complexes in 6 patients so studied. However, there was no correlation between apparent organ involvement and hypocomplementaemia and the levels of size of circulating immune complexes. It is concluded that the measurement of circulating immune complexes may be clinically useful in vasculitis, but that no direct evidence is yet available that they are pathogenetically related to those which are tissue-bound.

The following study was designed to examine the effect of the angiotensin converting enzyme (ACE) inhibitors captopril and enalapril on certain biological and physiological activities of isolated preparations of glomeruli from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive SHR rats. The results suggest that the contractile response of glomeruli from SHR to exogenous angiotensin II (Ang II) is significantly enhanced by captopril whereas it has a different effect on those from normotensive (WKY) rats. These effects are unrelated to changes in glomerular Ang II binding or the level of plasma renin activity (PRA), but they do depend partially on the sodium status of the animal. Whereas captopril induced a modest increase in the basal rate of prostaglandin E2 (PGE2) synthesis by glomeruli from normotensive (WKY) but not by those from SHR, the reverse occurred in the presence of Ang II. Prostaglandin E2 synthesis was increased in both strains of rats in the presence of excess arachidonic acid. Further increases occurred with the addition of captopril, these increases being significantly greater by glomeruli from WKY rats than by those from SHR, while enalaprilat had no effect on PGE2 production. The glomerular synthesis of PGE2 was not influenced in either strain of rats by in vitro administration of captopril.

The effect of serum from patients with renal failure on phenylalanine hydroxylase activity has been measured in normal individuals, patients with steady-state chronic renal failure and patients undergoing haemodialysis. Significant inhibition of enzyme activity was induced by serum from patients with steady-state chronic renal failure but not from patients undergoing haemodialysis. Inhibitor(s) was readily diffusible in vitro and appeared to have an approximate molecular mass of 800. The results suggest that the low-plasma tyrosine levels observed in patients with chronic renal failure are due, at least in part, to the inhibition of phenylalanine hydroxylase.

This is a rare, but potentially very troublesome disorder. We have been able to carry out detailed radiological, histological and biochemical investigations on 51 patients and the results of these investigations are presented. Considerable evidence of abnormal platelet activity has been found. The histological evidence has come from both biopsy and nephrectomy specimens and has shown aggressive atherosis leading to microembolic lesions and in some cases showing microaneurysm formation. In some instances this has led to areas of infarction both small and large. Most of the cases studied have been fully followed up and it has been found that despite the histological changes, the blood pressure remains normal and no demonstrable deterioration in renal function occurs. Attempts at treatment are described and discussed.

Clinical features have been correlated with renal function, histology and selective renal angiography in 19 patients with recurrent painless haematuria, recurrent loin pain, or both haematuria and loin pain in whom urinary infection, calculi and anatomical abnormalities of the urinary tract had been excluded. No deterioration in renal function was observed in any patient over periods of up to nine years. Although all patients showed similar glomerular changes histologically, consisting of focal and segmental mesangial thickening and proliferation and periglomerular fibrosis, mild tubular damage was more common in those with loin pain. All patients with loin pain whether or not they had haematuria, had abnormal renal angiograms consisting of focal or generalized vascular lesions sometimes associated with cortical infarcts. The possible aetiological factors are discussed with particular reference to oestrogen-containing compounds.

The concentration of free amino acids in the plasma and lumbar CSF of 11 patients with steady-state chronic renal failure has been measured and the CSF: plasma concentration ratios calculated. The results have been compared with the corresponding data from 37 control subjects. In renal failure, elevation of the mean plasma concentration of total amino acids and a reduction in the ratio of essential to total amino acids have been found. Whereas some individual plasma amino acid concentrations in renal failure were higher than normal, others were lower. Striking abnormalities of the CSF amino acid concentration have been observed. Some amino acids have shown similar patterns of abnormality in both CSF and plasma, whereas in the case of others, the changes have been restricted to either CSF or plasma. Significant variations from normal of the CSF: plasma concentration ratios were observed for four amino acids.

It is generally recognized that in many patients the ureteric obstruction and other manifestations of non-malignant retroperitoneal fibrosis will respond to treatment with corticosteroids. However, most surgeons are reluctant to use steroids as the primary treatment for patients with this condition, mainly because of the risk of mismanagement of malignant retroperitoneal fibrosis. Our experience in the care of 17 patients with non-malignant retroperitoneal fibrosis has led us to believe that an initial non-surgical approach is both safe and preferable.

The concentrations of inorganic ions and glucose in the plasma and CSF of 11 patients with "steady-state" chronic renal failure have been measured and their CSF: plasma interrelations studied. The results have been compared with the corresponding data from 34 control subjects. In the patients with renal failure, there was a positive correlation between raised CSF and plasma potassium concentrations. In contrast to the impaired potassium homeostasis, normal CSF magnesium and calcium concentrations were observed despite wide variations in the plasma concentrations of these ions.

The concentration of free amino acids in CSF and plasma has been measured in 19 patients with renal disease undergoing haemodialysis therapy. The values obtained have been compared with those measured in non-haemodialysed patients. At the end of a 10-h dialysis period, the total CSF amino acid concentration had fallen by only 23.3% compared with a 57.7% fall in plasma. Examination of the results for individual amino acid concentrations showed 3 different patterns of inter-relationship between plasma and CSF.

1. Angiotensin II (ANG II) binding and the physiological response to exogenous ANG II have been studied in isolated glomerular preparations from normotensive (NTR) and spontaneously hypertensive (SHR) rats. 2. The binding of 125I-labelled ANG II by glomeruli from SHR was significantly greater than that by glomeruli from NTR, whereas the binding affinity constant (Ka) showed that the SHR ANG II glomerular receptor had a lower affinity for the hormone than the NTR glomerular receptor. 3. Glomeruli from SHR were significantly less responsive to exogenous ANG II than those from NTR. 4. Sodium loading resulted in a significant increase in ANG II binding by glomeruli from NTR, whereas a decrease in binding occurred in glomeruli from SHR. 5. Although a high sodium intake caused a reduction in the response of glomeruli from both NTR and SHR to exogenous ANG II, these changes were not statistically significant. In NTR this was associated with a decrease in the concentration of agonist required to cause half-maximal response (EC50), whereas an increase in EC50 was shown by glomeruli from SHR.

The effect of an isotonic saline infusion on urinary sodium excretion and plasma renin activity (PRA) has been studied in 11 normotensive patients with a previous history of pregnancy-associated hypertension. The results have been compared with a group of controls matched for age, sex and parity. The results demonstrate an exaggerated natriuresis and a suppressed PRA response in the patients with a previous history or pregnancy-associated hypertension which is similar to those reported in patients with established 'essential' hypertension.

Eight adult patients with the nephrotic syndrome due to "minimal change" glomerulonephritis have been treated with cyclophosphamide alone. The effects of therapy have been compared with a similar group of patients treated with conventional diuretic therapy. Complete remission was achieved in seven of the cyclophosphamide treated patients as compared to only two spontaneous remissions in the untreated group. After a mean follow up period of 6 years none of these 9 patients relapsed. The eighth patient treated with cyclophosphamide remitted spontaneously 21 months after stopping cyclophosphamide and relapsed 36 months later. No serious side effects were encountered in the treated patients. The results suggest that cyclophosphamide is an effective agent in the management of adults with the nephrotic syndrome due to "minimal change" glomerulonephritis.

Although acute renal failure is a well recognized complication of several extra-hepatic biliary tract diseases especially biliary tract surgery in the presence of obstructive jaundice, there is little information concerning renal failure in acute cholecystitis. Renal function was assessed in 14 patients with acute cholecystitis and two with acute cholangitis. Six patients had no evidence of renal impairment, four had modest elevations of plasma urea and creatinine concentrations and six had acute reversible renal failure of whom three required peritoneal dialysis. Only one patient was hypovolaemic and in the remainder there was evidence that intravasular coagulation was responsible for the renal failure. It is suggested that bacteraemia was the initiating factor. The therapeutic implications of these findings are discussed.

Measurements of cerebrospinal fluid (CSF) and plasma amino acid concentrations have been made in 12 patients with the Guillain-Barré syndrome. The CSF protein concentration was normal in seven specimens and raised in 13. Abnormalities of the CSF amino acid profile were found in all specimens but were more marked in those with a raised CSF protein concentration. The possible causes and diagnostic significance of these changes are discussed.

1. Glomerular angiotensin II (ANG II) binding has been studied in normotensive (NTR) and spontaneously hypertensive (SHR) rats at 5, 10, 15 and 20 weeks of age. 2. Binding of 125I-labelled ANG II by glomeruli from NTR and SHR was similar at 5 and 10 weeks of age, with 5 week values of 426.4 (range 384-469) and 400.2 +/- 245 fmol/mg of protein; however, at 15 and 20 weeks ANG II binding by SHR glomeruli was significantly greater than by NTR, with 20 week values of 614.7 +/- 245 and 308.3 +/- 31.8 fmol/mg of protein, respectively (P less than 0.01). 3. The ANG II binding affinity constant (Ka) of glomeruli from NTR and SHR was comparable at 5, 10 and 15 weeks of age, with values of 1.5 (range 1.1-1.9) and 1.08 +/- 0.35 nmol/l, respectively, at 5 weeks; whereas at 20 weeks the Ka for SHR glomeruli was significantly greater than for NTR, with values of 1.85 +/- 0.45 and 0.66 +/- 0.22 nmol/l, respectively (P less than 0.001). 4. Age-related changes in glomerular binding of ANG II in SHR were not found to be related to changes in either plasma renin activity or systolic blood pressure.