A 22-year-old man weighing 50.5 kg and 165.5 cm in height was referred to our hospital on. December 27, 1977, with chief complaints of easy fatigability and numbness on right arm for two years. His blood pressure was 120/70 mmHg. Urinary volume varied from 1.4 to 2.3 L/day. The serum potassium was 2.1, sodium 138 and chloride 96 mEq/L. Arterial-blood gas analysis revealed metabolic alkalosis. Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were increased from 15.0 to 34.5 ng/ml/h, and from 25.5 to 55.9 ng/dl, respectively, after f urosemi.de and upright position on normal sodium diet. The dose of synthetic angiotensin II necessary to produce a rise of 20 mmHg in diastolic blood pressure was 45.0 ng/kg/min. Renal biopsy revealed an appa-rent hyperplasia of the juxtaglomerular complex. The followings are the results obtained by special examinations, including treatments with beta-adrenergic blockade (propranolol), indomethacin, oral angiotensin I-converting enzyme inhibitor (1-d-3-mercapto-2-methyl-propanoyl-l-prolin, SQ 14225), spironolactone and potassium chloride. I) Propranolol decreased both PRA and PAC to a some extent, but neither the hypokalemic alkalosis nor the vaasoreactivity to angiotensin II was improved. II) Indomethacin decreased the urinary excretion of prostaglandin-E from 6000 to 200 (normal, below 1000) ng/day and normalized both hyperaldosteronemia and vasoreactivity to angiotensin II. However, hypokalemic alkalosis and sodium loss in the urine were not corrected. III) The serum potassium did not increase by the treatment with spironolactone, but first increased from 2.4 to 3.3 mEq/L with an administration of potassium chloride, IV) SQ 14225 depleted the blood pressure from 118/60 to 90/35 mmHg with an increase in PRA from 21.5 to 44.8 ng/ml/h at 90 minutes after the administration. However, PAC was decreased from 28.6 to 14.4 ng/dl. V) A significant relationship (r=0.905, p >0.01) was observed between PRA altered by infusions of saline or dextrose, administration of propranolol, indomethacin or spironolactone and the dose of synthetic angiotensin II required to elevate 20 mmHg in diastolic blood pressure. These data strongly suggest that the receptor sites in both arteriolar smooth muscle and adrenal cortex are not impaired in this disorder, and that primary salt and potassium wasting has an important role in the pathogenesis of Bartter's syndrome.

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The effect of vitamin D₂ (VD₂) supplementation on hypocalcemia in 54 hypocalcemic patients (29 males and 25 females) on chronic hemodialysis were studied. Calcium lactate (3 g/day), or VD₂ (10, 000 IU/day, 50, 000 IU/day, and 80, 000 IU/day) were administered for 4 months in order to cor-rect hypocalcemia observed in all patients before treatment. Serum calcium, phosphate and alkaline phosphatase levels were measured and the effects of VD₂ supplementation of these parameters of calcium metabolism were also studied. 1) Calcium lactate, or 10, 000 IU/day of VD₂ were not effec-tive for the correction of hypocalcemia, while the administration of 50, 000-80, 000 IU/day of VD₂ were effective. The effects of VD₂ supplementation on serum calcium concentration were dose-dependent, and the normalization of serum calcium concentrations was achieved more rapidly with higher dose of VD₂. However, in the group treated with 80, 000 IU/day of VD₂, many patients showed hypercalcemia, but in the group treated with 50, 000 IU/day of VD₂i only a few patients showed it. From these results, suitable doses (initial and maintenance doses) of VD₂ in Japanese dialysed patients will be 50, 000 lU/day. 2) When the responder group (normal serum calcium levels after 4 months of treatment with 50, 000 IU/day of VD₂) and the non-responder group (less than 4.2 mEq/liter of serum calcium concentration on the same condition) were compared, the duration of dialysis were significantly shorter in the former than those in the latter. This fact may suggest that the effects of VD₂ administration on hypocalcemia under chronic dialysis treatment are partly dependent on the residual renal function through the conversion of 25- (OH) -D₃ into 1, 25 (OH₂) D₃.

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Abnormal lactation (galactorrhea) was observed in an uremic male patient aged 31, maintained on regular dialysis treatment (RDT). Proteinuria was firstly pointed in 1971, and he was diagnosed as chronic glomerulonephritis by renal biopsy. RDT was started in January 1977. Patient noticed abnormal lactation in January of 1978 by himself. At this time, he had been given hydroxy-alumi-nium gel, mufti-vitamin powder, a-methyldopa, chlorpheniramin maleate and methochlopramide. Simple and computed axial tomography revealed no abnormality in sella turcica. Basal prolactin levels in the blood showed very high value; 839-1373 ng/ml (normal ranger 2.0-20.0 ng/ml). Prolactin response to TRH infusion (500, ug) was negative. The response of FSH and LH to LH-RH infusion (100 fig) was also negative. These results suggest hypothalamo-pituitary dysfunction in this case. Basal LH level (99.9 mIU/ml) was high and testosterone was low (410 ng/100 ml) in normal range (300-850 ng/100 ml). These facts suggest that he had been in a state of hypogonadism. Four weeks after the cessation of drugs, we could not observe any change in lactation degree. In an attempt to diminish lactation, L-dopa was administered, but in vain. Then, CB 454 was administered (5 mg/day×45 days), and gradual decrease of lactation was observed, and prolactin was recovered to subnormal level. With cessation of CB-154, prolactin elevated to 78-234 ng/ml and the lactation reincreased apparently. The composition of his secreted milk was abundant in sodium, potassium and C8_14 saturated fatty acids compared to normal milk. It is concluded that the lacta-tion of this patient is induced by the long-term administration of a-methyldopa. Hypothalamo-pitui-tary dysfunction and hypoganadism are also contributing factors for lactation in this case, as ob-served in female cases with abnormal lactation.

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Renal biopsy specimens from 67 cases with SLE were analysed to investigate the relationship between clinical data and their light & electron microscopic findings. The classification of glomerular lesions and their percentage were as follows: normal or minimal change (4.5%), diffuse proliferative gl-n. (74.6%), focal & segmental gl-n. (4.5%), membronous gl-n. (8.9%) and membranoproliferative gl-n. (7.5%). In the characteristic findings by electron microscopy, dense deposits were found in 91.0% of 67 cases and mesangial deposits were common and found in 91.8% of cases with deposits. In 6.6% of dense deposits observed, there was an organised apperance (“fingerprint pattern”) composed of straight or curved parallel microfilaments. In addition to glomerular deposits, microtubular inclusions and spherical microparticles were found in 73.1%, 11.9% respectively. Cases without deposits or only with measangial deposits tended to show scanty proteinuria, on the other hand, all cases with massive proteinuria had subepithelial deposits. In untreated cases, low serum complement and positive anti-DNA antibodies were found more frequently in minimal and diffuse proliferative gl-n. than in membranous gl-n. Prognosis of cases with diffuse proliferative gl-n. having massive subendothelial deposits seemed to be poor. Seven cases were rebiposied four months to seven years later. Three of seven cases showed the transformation of its morphologic patterns on light microscopy.

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Aluminium concentrations in plasma, red blood cells and hair were measured in 12 undialyzed and 23 hemodialyzed patients with chronic renal failure (CRF). Hair concentration of AI was meas-ured by neutron activation analysis and Al concentrations of plasma, red blood cells and dialysate were measured by flameless atomic absorption analysis. Plasma concentration of Al was significantly higher in both undialyzed (51±23 li/L, p<0.01) and hemodialyzed (50+ 28, p>0.01) patients than in the control group (27±9, n=13). Al concentration in red blood cells was significantly elevated in both undialyzed (100±30μg/L, n=10, p<0.05) and dialyzed (150±30, n=10, p<0.001). Patients compared with that of the control group (70±20, n= 10). Hair concentration of Al in undialyzed patients (370±266 ppm, n = 5, p <0.l) was significantly higher than that of the control group (97.0±24.9 ppm, n=9). Plasma concentration of Al significantly increased during a single dialysis when dialysate, pre-pared from softened tap water, was used, but did not when dialysate, prepared from reverse osmosed water, was used. Dialysate prepared from softened water contained Al at a concentration of 28±16μg/L (n=9), whereas dialysate prepared from reverse osmosed water contained Al less than 10μg/Lm In hemodialyzed patients, duration of dialysis positively correlated with plasma concentration of Al (r=0.548, n=23, p<0.001) and with hair concentration of Al (r=0.686, n=8, p<0.1). In conclusion, these results indicate that Al accumulates in plasma, red blood cells and hair of patients with CRF. Al accumulation in dialyzed patients was primarily caused by its transfer from dialysate prepared from tap water or softened water during hemodialysis. Al accumulation in dia-lyzed patients may be avoid by preparing dialysate from water treated by reverse osmosis system.

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Injection of rabbit anti-GBM serum caused severe glomerular lesions similar to Masugi nephritis in congenitally athymic nude mice and their syngeneic normal littermates. Glomerular swelling, mesangiolysis, capillary wall thickening, fibrin deposition, focal necrosis of the tufts and infiltration of PMNs and monocytes were observed in glomeruli of both mice. But the proliferation of glomerular cells were not so marked. Linear deposition of rabbit IgG, and mouse IgG, IgM, C3 were usually seen. Morphologically and immunohistologically, there were no significant differences between both mice. From these results, it is suspected that cellular immunity may not play an important role in the development of Masugi nephritis.

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The interrelationship between Renin-Angiotensin-Aldosterone (R-A-A) system and renal prosta-glandin E (PGE) was studied in essential hypertension and primary aldosteronism. Urinary PGE, converted to PGB before extraction, was measured by radioimmunoassay using PGE antiserum. The accuracy and reproducibility of this method was excellent enough to determine the level of urinary PGE. Urinary excretion of PGE was significantly decreased in patients with essential hypertension and primary aldosteronism compared with that of normal subjects. In essential hypertension and normal subjects, there was no significant correlation between plasma reamn activity (PRA) and urinary excretion of PGE but a significant positive correlation was found between urinary excretion of sodium and that of PGE. Urinary excretion of PGE was not decreased in low renin essential hyper-tension. No obvious relationship was observed between the changes in PRA and urinary excretion of PGE during the stimulation of renin release. After the restriction of sodium intake urinary ex-cretion of PGE was significantly decreased in spite of the marked increase in PRA and plasma aldo-sterone concentration (PAC). These data does not support that R-A-A system is the main regu-lator of renal PGE synthesis. It was suggested that renal PGE may play a role in renal sodium handling. In primary aldosteronism, aldosterone antagonist which reduced the urinary excretion of kallikreinn in our previous experiment did not decrease the urinary excretion of PGE, suggesting no direct relationship between renal kallikrein-kinin system and renal PGE synthesis in man. Thus, aldo sterone may not stimulate the renal PGE synthesis, though it activates the renal kallikrein-kinin system. In essential hypertension, R-A-A system was activated by the administration of furosemide and low sodium diet. The addition of indomethacin significantly decreased the urinary excretion of PGE and reduced the enhanced PRA and PAC to control level. It was suggested that the renal prostaa glandins play an imporsant role in renin release.

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Plasma catecholamine concentration and plasma dopamine-beta-hydroxylase (DBH) activity were studied in 22 subjects undergoing choronic hemodialysis. Significantly raised plasma norepinephrine (NE) concentration and reduced plasma DBH activity were observed in these subjects resting supine for 1 hour prior to hemodialysis. During the hemodialysis, plasma NE concentration was increased remarkably and returned promptly to pre-dialysis values after stopping the dialysis, whereas plasma epinephrine concentration was increased gradually through the late and post-dialysis period. Plasma DBH activities showed a gradual increase along with the lapse of dialysis. But, these variations were not statistically significant, when the values were tested with correcting its relative changes by those of total protein concentration in the plasma. The variations of plasma NE concentrations during hemodialysis correlated negatively with those of mean arterial pressures or positively with those of heart rates, plasma protein concentrations and hematocrits, respectively. Severe hypoten-sive episodes during dialysis were associated with a comparable rise in plasma NE to those in other normptensive and hypertensive patients. Plasma catecholamine concentration appears to be a more sensitive marker of sympathetic nervous activity in dialyzed patients than plasma DBH activity, although both indices might be influenced not only by sympathetic nervous activity, but also by several foctors related directly to the condition of renal failure. Remarkable changes of plasma NE concentrations during the hemodialysis indicate that sympathetic nervous system is of primary im-portance to maintain the blood circulation against the rapid depletion of extracellular fluid volume induced by this procedure.

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