The reversed ratio of 1-84 PTH (whole PTH)/intact PTH in a patient on hemodialysis associated with primary hyperparathyroidism.

Intact PTH measures not only 1-84 PTH, but also other fragments such as 7-84 PTH. Lately, a measurement of 1-84 PTH has been available as whole PTH assay and the ratio of whole PTH/intact PTH is considered to be between 0.5 and 0.7 in patients on hemodialysis. Therefore, intact PTH should be higher than whole PTH. We present a 57-year-old male with chronic renal failure on hemodialysis whose whole PTH was higher than intact PTH (the reversed ratio of whole PTH/intact PTH). He showed one enlarged parathyroid gland by an ultrasonic test, CT examination and RI subtraction study. After this gland was removed by surgery, the ratio of whole PTH/intact PTH normalized. The size of the resected gland was 22 x 15 x 11 mm. The histologic examination revealed adenoma. This indicates that, if patients with chronic renal failure showed the reversed ratio of whole PTH/intact PTH, the possibility that they could have primary hyperparathyroidism in addition to secondary hyperparathyroidism should be considered.

Cisplatin-incorporated polymeric micelles eliminate nephrotoxicity, while maintaining antitumor activity.

cis-Diamminedichloroplatinum (II) (cisplatin, CDDP), a potent anticancer agent, was bound to the aspartic acid residues of poly(ethylene glycol)-poly(aspartic acid) (PEG-P(ASP)) block copolymer by ligand substitution reaction at the platinum atom of CDDP. The polymeric drug thus obtained was observed to form a micelle structure in aqueous medium, showing excellent water solubility. In the present study, in vitro and in vivo antitumor activity against several human tumor cell lines, toxicity and pharmacokinetic characteristics in rodents of CDDP-incorporated polymeric micelles (CDDP / m) were evaluated in comparison with those of CDDP. In vitro, CDDP / m exhibited 10 - 17% of the cytotoxicity of CDDP against human tumor cell lines. CDDP / m given by intravenous (i.v.) injection yielded higher and more sustained serum levels than CDDP. In vivo CDDP / m treatment resulted in higher and more sustained levels in tumor tissue than CDDP, and showed similar antitumor activity to CDDP against MKN 45 human gastric cancer xenograft. CDDP / m treatment caused much less renal damage than CDDP. These results indicate that CDDP / m treatment can reduce CDDP-induced nephrotoxicity without compromising the anticancer cytotoxicity of CDDP.

Wegener's granulomatosis with onset of acute pancreatitis and rapid progress. A case report.

Although Wegener's granulomatosis is a rare disorder, the clinical and histological characteristics are well known. However, Wegener's granulomatosis with the onset of acute pancreatitis has rarely been reported. We discuss the case of Wegener's granulomatosis in a 65-year-old man, presenting with acute pancreatitis and whose disease progressed rapidly.

Therapeutic results of primary aldosteronism with special reference to renal or renovascular lesions.

A study was made of 9 patients with primary aldosteronism due to aldosterone-producing adenoma (APA) and 8 subjects with idiopathic adrenal hyperplasia (IHA) to clarify the pathogenesis of sustained hypertension after surgical or non-surgical treatment. Following each treatment, a complete improvement of hypertension was obtained in 12 patients (6 APA, 6 IHA), while 5 (3 APA, 2 IHA) showed still hypertensive status. Renal or renovascular lesions were prominent only in the hypertension-unchanged group. Under regular sodium diet, the ratio of urinary excretion of sodium to creatinine of this hypertensive group was significantly lower than that of the hypertension-improved group. However, the results of other renal function tests were similar in both groups. After respective treatments, suppressed plasma renin activity and elevated plasma aldosterone concentration were improved in all patients. In addition, patients of both groups showed normal response of the renin-aldosterone system following diuretic and dietary induced sodium and volume depletion. Based on these findings, renal or renovascular lesions appear to play an important role in the pathogenesis of maintenance of hypertension in this disorder after respective treatments.

Membranoproliferative glomerulonephritis associated with chronic hepatitis B in adults: pathogenetic role of HBsAg.

Two adult cases of membranoproliferative glomerulonephritis (MPGN) associated with chronic hepatitis B were reported. Serum HBsAg, HBeAg and anti-HBc were positive. Glomerular changes were essentially the same in both patients and consistent with MPGN type III. Immunofluorescence microscopy revealed diffuse granular and lumpy deposits of IgG, IgA, IgM, C1q and C3 along glomerular capillary walls and in mesangial areas. Granular deposition of HBsAg was observed along capillary walls and in mesangial areas, and the staining patterns were similar to those of immunoglobulins and complements in both patients. Glomerular deposition of HBeAg, however, was negative in one case, and only slight and segmental in the other case. These findings suggest that HBsAg rather than HBeAg may play a role in the pathogenesis of MPGN associated with hepatitis B virus infection in adults.

Effect of the anticomplementary agent, K-76 monocarboxylic acid, on experimental immune complex glomerulonephritis in rats.

We examined the effect of the anticomplementary agent K-76 monocarboxylic acid (K-76COOH), which is known to inhibit C5 activity, on immune complex glomerulonephritis in rats. Bovine serum albumin (BSA) nephritis was induced in rats by subcutaneous immunization and daily intravenous administration of BSA. K-76COOH (30 mg/kg) was administered intraperitoneally twice daily for 4 weeks. It was shown that K-76COOH would significantly reduce the development of proteinuria in the early stage of BSA nephritis, but it failed to suppress proteinuria in the late stage. There was no significant difference in glomerular changes between treated animals and non-treated controls. These findings suggest that C5, and the terminal complement components may play a significant role in protein excretion in the early stage of immune complex glomerulonephritis.

Cardiovascular effects of ketanserin in conscious rabbits.

The antihypertensive effects of intravenous injection of ketanserin, a 5-HT2 receptor antagonist, were assessed in conscious rabbits. In intact rabbits, ketanserin lowered blood pressure in a dose-dependent manner. The antihypertensive effects of ketanserin were also observed in rabbits with two-kidney, one clip (2K1C) hypertension and with one-kidney, one clip (1K1C) hypertension. The effect was more marked in the 1K1C rabbits with low plasma renin activity (PRA) and high plasma norepinephrine (PNE) than in 2K1C rabbits with high PRA and normal PNE. The heart rate was not changed. Ketanserin suppressed the pressor response to exogenous norepinephrine (0.6 micrograms/Kg) 15, 30 and 45 min after the injection of ketanserin (1 mg/Kg). It also suppressed the pressor response to phenylephrine (3 micrograms/Kg) 15 min after the injection, but it did not suppress the pressor response to angiotensin II (0.15 micrograms/Kg). In order to investigate baroreceptor function, balloons were placed around the abdominal aorta and the inferior vena cava and inflated alternately. Thus, the mean arterial pressure vs heart period-logistic curve was obtained under steady-state conditions. There were no changes after the drug administration in the range of heart period and the gain (the slope at midpoint of the curve). These results suggest that the inhibition of pressor response of norepinephrine has effects in addition to a direct vasodilatory action and that an alteration of baroreceptor function is not involved in the antihypertensive effects of ketanserin.

Effect of the antiplatelet agents ticlopidine and dipyridamole on experimental immune complex glomerulonephritis in rats.

The effect of the antiplatelet agents ticlopidine and dipyridamole on immune complex glomerulonephritis in rats was evaluated. Bovine serum albumin (BSA) nephritis was induced in rats with subcutaneous immunization and intravenous dosage of BSA. Ticlopidine and dipyridamole were administered for 4 weeks before and for 7 days after onset of proteinuria. It was shown that both ticlopidine and dipyridamole could reduce the development of proteinuria when administered before the onset of proteinuria. Ticlopidine also reduced the amount of urinary protein after onset of proteinuria, and may thus be more effective against urinary protein excretion. When the antiplatelet agents were administered before onset of glomerulonephritis, blood urea nitrogen and serum creatinine levels were significantly lower, and glomerular hypercellularity and mesangial widening were milder in animals treated with ticlopidine than in controls. Glomerular deposition of BSA was less intense in treated animals than in nontreated controls. Thus, ticlopidine as well as dipyridamole was found to inhibit the development of proteinuria and glomerular alteration. It is suggested that ticlopidine could be more effective than dipyridamole against the development of immune complex glomerulonephritis in rats.

N-(3',4'-dimethoxycinnamoyl)anthranillic acid, an antiallergic compound, induced eosinophilic cystitis.

Eosinophilic cystitis developed in an asthmatic patient after therapy with the antiasthmatic agent, Tranilast. The progress of this patient and the histopathologic findings of bladder biopsy specimens are reported. A review of recent publications on the possible causative correlations is presented. It appears judicious to perform bladder biopsy if common chemotherapy fails to improve bladder irritability in patients receiving Tranilast therapy. If a diagnosis of eosinophilic cystitis induced by Tranilast is established, immediate withdrawal of the drug with or without steroid therapy is recommended.

Glomerular deposition of IgA in experimental hepatic cirrhosis.

Wistar rats rendered cirrhotic with carbon tetrachloride excreted significant proteinuria and hematuria. Serum levels of IgA and IgG were significantly elevated in cirrhotic animals. They showed mild mesangial proliferation and immunofluorescent studies revealed deposits of IgA and IgG predominantly in mesangial areas and along capillary walls. These findings were very similar to those seen in patients with hepatic cirrhosis or IgA nephropathy. The deposits of IgA were also found in hepatic tissue from cirrhotic animals. The intensity and distribution of glomerular IgA deposits were not diminished after treatment with acid buffer. These results suggest that glomerular IgA are IgA polymers and decreased hepatic clearance of hepatic IgA polymers may be responsible for the glomerular deposition of IgA.

Acute interstitial nephritis with bone marrow granulomas and uveitis.

A case of interstitial nephritis with bone marrow granulomas and uveitis was presented. A 53-year-old woman was found to be uremic in the course of rheumatoid arthritis. The renal biopsy revealed acute interstitial nephritis with eosinophilic infiltration. She also had bone marrow granulomas and uveitis. These findings were compatible with those of the syndrome described by Dobrin et al. The etiology and the pathogenesis of this syndrome remain unknown. However, the elevation of the erythrocyte sedimentation rate, raised levels of serum immunoglobulins, presence of circulating immune complexes and decreased T-cell population observed in this patient suggest the involvement of immunological disorders.

Membranous glomerulonephritis associated with enterococcal endocarditis.

An autopsy case of membranous glomerulonephritis associated with enterococcal endocarditis was reported. Although enterococcal antigen was not identified in glomerular deposits, the eluate from the patient's renal tissue was shown to specifically recombine with cells of the enterococcus isolated from his own ante mortem blood. Hypocomplementemia, circulating immune complexes and antienterococcal antibodies were also observed. These findings suggest that enterococcus-related immune complexes played a role in the pathogenesis of glomerulonephritis associated with enterococcal endocarditis in this patient.

Effects of captopril on the renal hemodynamics during aprotinin infusion in anesthetized dogs.

The effect of captopril (SQ 14,225) on the renal hemodynamics, cortical plasma flow (CPF) and noncortical plasma flow (NCPF), was studied in sodium-replete anesthetized dogs during aprotinin infusion. Mean blood pressure (MBP) increased by aprotinin (p less than 0.05) and decreased by captopril (p less than 0.02). Renal vascular resistance (RVR) tended to increase by aprotinin and decreased from 1.29 to 0.86 mm Hg/ml/h (74.7%) by captopril (p less than 0.05). Renal vein renin activity (RRA) inclined to decrease by aprotinin and increased from 17.8 to 47.2 ng/ml/h (278.2%) by captopril (p less than 0.05). Although the administration of captopril alone did not alter the renal hemodynamics despite the reduction of MBP, captopril made a recovery of renal plasma flow (RPF), CPF and NCPF which had decreased by aprotinin. Especially, CPF showed a significant recovery from 45.4 to 55.6 ml/min (123.6%) by captopril (p less than 0.02). These results indicate that the inhibition of endogenous angiotensin made a preferential increase in CPF and suggest that the renin-angiotensin system plays a major role in the effect of captopril of the renal hemodynamic changes.