[Bone fracture receiving LH-RH agonists for prostatic cancer].

BACKGROUND: Luteinizing hormone-releasing hormone (LHRH) agonists are popularly used drugs in the treatment of prostatic cancer. However, it has been reported that continuation of a low testosterone level following a longterm administration of these drugs reduces the bone mineral density and makes for osteoporosis, which is accountable for fracture, we measured the bone mineral density and bone metabolic markers in the cases who suffered fracture receiving LHRH agonists for prostatic cancer. PATIENTS AND METHODS: Between 1994 and 1998, 196 patients (mean age 78.1 years) were treated with LHRH agonists for prostatic cancer. Of these patients, 13(7%) who had bone fracture during treated with LHRH agonists were divided into fracture group, and 70 patients who had not bone fracture divided into non-fracture group. Fracture by traffic accident was excluded. The bone density in the third lumbar vertebra was measured using quantitative computed tomography (QCT). Osteocalcin, 1, 25- (OH)2 vitamin D, urinary type 1 collagen cross-linked N-telopeptides (NTx), parathyroid hormone (PTH) and calcitonin were measured as bone metabolic markers. RESULTS: The mean age of fractured cases was 78 years. The period from the start of treatment to fracture was 11 to 45 months (mean 27 months). No case of fracture at the site of metastasis of prostatic cancer was found. The bone density was significantly low in the fracture group compared with that of non-fracture group. Of the bone metabolic markers, NTx showed high values in the fracture group. CONCLUSION: There is a need to measure bone mineral density and bone metabolic markers periodically and to evaluate secondary osteoporosis in the patients receiving LHRH agonists for prostatic cancer.

[Diagnostic value of urinary N-telopeptide of type I collagen in prostate cancer: comparison with bone scintigraphy].

The usefulness of a new biochemical marker of bone resorption, N-telopeptide of type I collagen (NTx), in the diagnosis of bone metastasis was assessed in 69 prostate cancer patients. Based on the bone scintigraphy findings, the patients were divided into a bone metastasis (+) group (n = 36) and a bone metastasis (-) group (n = 33). The urinary NTx level was significantly higher in the bone metastasis (+) group than in the bone metastasis (-) group (95.5 +/- 18.5 nM BCE/mM Cr vs. 63.3 +/- 7.9 nM BCE/mM Cr). There was a tendency for greater variability in urinary NTx levels during a 2 month-period in the bone metastasis (+) group than in the bone metastasis (-) group. The urinary NTx level of the 6 patients who were clinically staged as (4+) according to the extent of disease (EOD) grading system was 211.4 +/- 96.9 nM BCE/mM Cr, and was significantly higher (p < 0.05) than in the (-) group. However, there was not a significant difference in urinary NTx levels between the (1+) to (3+) groups and the (-) group. In conclusion, measuring urinary NTx levels in useful in diagnosing bone metastasis in view of the fact that it is a simple and noninvasive procedure. While it is not as sensitive as bone scintigraphy, it may be used to supplement bone scintigraphy.

[A case of ectopic familial pheochromocytoma].

This is a report of the occurrence of familial ectopic pheochromocytoma in two brothers, whose father had bilateral adrenal pheochromocytoma. Both brother complained of hypertension. In the first case, a 22-year-old man presented with much higher than normal norepinephrine. Abdominal CT and chest CT scanning and 123I-MIBG scintigraphy revealed an extraadrenal tumor in the chest on the bilateral adrenal grands. Bilateral adrenectomy was performed. In the second case, the 20-year-old brother was found to have an abdominal mass that was diagnosed as ectopic pheochromocytoma originating in the intra-abdominal paraaorta according to abdominal CT scanning and 131I-MIBG scintigraphy. The tumor was resected.

[Clinical study of Silver Lubricath Foley catheter].

We evaluated the Silver Lubricath Foley Catheter (silver catheter) coated with silver and hydrogel developed to prevent urinary infection, in comparison with the silicone-coated catheter (silicone catheter). Twelve patients ranging from 71 to 95 years of age (median age, 82 years) were catheterized and the 16 of 18F catheter was replaced every 2 weeks. They answered a questionnaire which included inquiry about the treatment with urinary catheter. Because of less leakage and discomfort to the urethra, the silver catheter had advantages over the silicone catheter. The risk of bacteriuria after 14 days of catheterization was not significantly different between the two types of catheter. Scanning electron microscopic analysis revealed that bacterial biofilm developed on the inner surface of both catheters after 14 days of catheterization. On the other hand, the amount of bacterial biofilm on the outer surface of a silver catheter was less than that on the outer surface of a silicone catheter.

[A case of muscle metastasis of renal cell carcinoma treated by local resection and tensor fascia lata myocutaneous flaps].

A 44-year-old male with a little finger tip-sized tumor palpable on the left epigastric wall and a left renal tumor detected on computerized tomography (CT) was referred to this hospital in June 1991. Nephrectomy was performed in July 1991 under the diagnosis of a left renal tumor. Histologically, the tumor was a renal cell carcinoma, grade 2, clear and granular cell type. The tumor in the left abdominal wall was not extracted. As a tumor also developed in the scapular tunica muscularis, tumors in the left musculus rectus abdominis and the scapular tunica muscularis were extracted to the extent possible in July of 1992. Histologically, these tumors were metastatic clear cell carcinomas. The tumor in the left musculus rectus abdominis recurred and another was palpable in the left lateral femur. In August of 1993, the tumors in the left musculus vastus lateralis and the left musculus abdominis were extracted together with the tunica muscularis, and the defective region on the abdominal wall was closed with a left musculus tensor fascia lata flap. No evidence of recurrence has been observed to date.

Renal gluconeogenesis in man: comparison with rats and rabbits.

To provide evidence on renal gluconeogenesis in humans and to compare with rats and rabbits, glucose production from several substrates was determined using cortical slices of the three species. In humans, the normal parts of kidney tissue were obtained from six cases of transitional cell carcinoma of the renal pelvis and four cases of renal cell carcinoma. Renal cortical slices were incubated aerobically with or without substrates, and the glucose contents were assayed photometrically. The specificity of human kidneys was evaluated by comparison with the results obtained from rats and rabbits. The rank order of renal gluconeogenesis from various substrates was as follows: Humans: pyruvate > oxaloacetic acid > lactic acid > fructose-1,6-diphosphate > L-glutamine. Rats: pyruvate > fructose-1,6-diphosphate > oxaloacetic acid > lactic acid > L-glutamine. Rabbits: fructose-1,6-diphosphate > pyruvate > oxaloacetic acid > lactic acid >> L-glutamine = 0. In general, the human kidney can produce glucose at the lowest rate among the three species. The substrate specificity of humans was more or less similar to that of rats. These results suggest the existence of a species difference in renal gluconeogenesis both in substrate specificities and quantitative activities.

[Study of nephrotoxicity through glutathione metabolism by cisplatin (CDDP) and adriamycin (ADM) in rat kidneys].

We studied cytotoxicity in vitro through reduced glutathione (GSH) metabolism by cisplatin (CDDP) and adriamycin (ADM) in rat kidneys. Renal cortical slices of Fischer 344 rats were incubated with Krebs-Ringer buffer containing CDDP (0-5mM) or ADM (0-0.5 mM). GSH and glutathione reductase (GSSG reductase) in these renal cortical slices were determined. Cell viability was assessed by lactate dehydrogenase (LDH) leakage. The following results were obtained. 1) Intracellular GSH in renal cortex was decreased by CDDP dose- and time-dependently. 2) The activity of GSSG reductase was suppressed by CDDP, but not by ADM. 3) LDH leakage increased significantly with CDDP and ADM respectively. 4) The incubation of renal cortical slices with GSH exogenously protected the increase of LDH leakage induced by CDDP or ADM. 5) The coincubation of renal cortical slices with CDDP and ADM did not increase LDH leakage compared with single administration of ADM. 6) LDH leakage in incubation with ADM after incubation with CDDP increased remarkably. The viability of renal cortical slices was more damaged by ADM under the condition of depleted GSH by CDDP. Therefore, it seemed that the order of administration was very important in combination chemotherapy.

[Study on gamma-GTP activity in urine and renal tissue of drug-induced nephrotoxicity in rats].

We investigated changes of urinary and renal gamma-glutamyl transpeptidase (gamma-GPT) activities in rat with renal damages caused by nephrotoxic agents in order to clarify the onset and the course of these nephrotoxicities. Cisplatin (CDDP) which is an antitumor agent, cephaloridine (CER) which is the first-generation cephem, and gentamicin (GM) which is an aminoglycoside were employed as tested nephrotoxic agents. We administered three fourth of LD50 of each agent to male Fischer 344 rats, intra-peritoneally. And the time-course changes of serum creatinine (s-Cr) value, creatinine clearance (Ccr) and urinary gamma-GTP activity were observed after administration of each agent. Finally, we measured renal gamma-GTP activities and observed pathological changes of the kidneys. The elevation of s-cr values and the reduction of Ccr appeared 3 days and 12 hours after the administration of CDDP and CER, respectively. And the peak appeared 7 days and 3 days after the administration of CDDP and CER, respectively. Increase of urinary gamma-GTP activities occurred earlier than the peak of s-cr value and Ccr in each group and as early 12 hours after the administration. In CER groups, the peak of urinary gamma-GTP activities was observed within 12 hours after the administration. And the peak of urinary gamma-GTP activities was observed at 24 hours and in 3 days after the administration of GM and CDDP, respectively. In addition, renal gamma-GTP activities reduced around 40% of those of control.(ABSTRACT TRUNCATED AT 250 WORDS)

[Recurrence presenting as anuria at 16 years after partial nephrectomy for a pelvic tumor in a solitary kidney: a case report].

A 61-year-old male underwent right partial nephrectomy for a pelvic tumor of a solitary kidney at the former hospital on April 1975. Two years later he had a small bladder tumor and transurethral resection was performed. Since August 1985 he had been followed up in our hospital. On June 1986, the urine cytology showed class V, but neither cystoscopy nor drip infusion pyelography revealed the tumor. On January 1992, he consulted our department with macrohematuria and anuria. Serum creatinine and blood urea nitrogen level were 17.24 mg/ml and 84.1 mg/ml, respectively. Hemodialysis was administered. Retrograde pyelography revealed a defect of tumor at the pyeloureteral junction, and pyuria by ureteral catheterization showed class V cytology. Abdominal CT showed right hydronephrosis caused by the recurrence of pelvic tumor, and right nephrectomy was performed. The histopathological diagnosis was non-papillary transitional cell carcinoma, grade 3 > 2, pT3. He is in good condition with maintenance hemodialysis. In the Japanese literature there were 16 cases of pelvic tumor on the solitary or residual kidneys. In 12 of the 16 cases, kidney sparing treatment was tried and only our case has lived over 10 years. The indication of partial nephrectomy for pelvis tumor was discussed.

[Alterations of gluconeogenesis by ischemic renal injury in rats].

This study was designed to determine changes in one of metabolic functions, gluconeogenesis after ischemic renal injury. Right kidneys of SD rats were removed and a vascular clamp was placed across the left renal artery and vein for 0, 10, 30, 60 and 90 min. On 1, 3 and 7 days after the treatment, tubule suspensions were prepared by collagenase treatment of left kidneys and incubated with or without 2 mM pyruvate or malate aerobically. After the incubation, glucose contents were assayed photometrically. Serum creatinine was also determined. In addition, morphological changes were observed under light microscopy to examine the relationship between metabolism and morphology. The tendency of increase of gluconeogenesis was observed on day 1 and 3 after 10, 30, 60 min of ischemic time. On the other hand, gluco-neogenesis decreased significantly on day 1 after 90 min treatment. In contrast, on day 1 and 3 after treatment, serum creatinine levels showed no difference from control at the groups of 10 and 30 min ischemia. Whereas it rose significantly at the group of 60 min ischemia, showing a different tendency from that of the increase of gluconeogenesis. Moreover, morphologic damage was observed on day 1 and 3 after ischemia of 30 and 60 min. The morphologic damage was found more advanced in the corticomedullary region than those of the cortex which has the high gluconeogenic activity and which thus showed relatively limited damage. These results suggest that renal gluconeogenesis is relatively insusceptible to ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations of gluconeogenesis by ischemic renal injury in rats.

This study was designed to determine changes in one metabolic function, gluconeogenesis (GLG), after ischemic renal injury. Tubule suspensions were prepared by collagenase treatment of SD rat kidneys on 1, 3, and 7 days after left renal artery and vein occlusion for 0-90 min and incubated in Krebs-Henseleit buffer with or without 2 mM pyruvate or malate aerobically. Glucose contents were assayed photometrically. On days 1 and 3 after ischemia for longer than 60 min, serum creatinine levels rose significantly. The tendency of increase of GLG was observed on days 1 and 3 after 10-60 min of ischemia. GLG increased significantly on day 1 after 30-min ischemia. On the other hand, GLG decreased significantly on day 1 after 90-min treatment. Morphologic damage was limited to the corticomedullary region on days 1 and 3 after ischemic times of 30 and 60 min. These results suggest that renal GLG is stimulated to supply energy for ATP decrease by ischemia and for further regeneration in extraproximal segments along the nephron.

Changes in the cerebral vascular bed in experimental hydrocephalus: an angio-architectural and histological study.

The angio-architectural and histological changes of small cerebral blood vessels in experimental hydrocephalus were studied to assess the changes of the vascular bed in the cerebral mantle. Change of the microvasculature assessed from microcorrosion casts by scanning electron microscopy (SEM) and the histological changes shown by light and electron microscopy were compared before and after shunting for hydrocephalus. The changes of the rCBF were also evaluated by the hydrogen clearance method. In hydrocephalus, a reduction in the number and caliber of the capillaries was noted in both the white and gray matter in the SEM study, but the capillaries were preserved and changes were mild and nonspecific in the electron microscopic examination. Shunting resulted in the reversal of all these changes to normal along with recovery of the rCBF, which had decreased in hydrocephalus. These observations suggest that changes of the vascular bed participate in the alteration of cerebral mantle width in the hydrocephalic process, and that the changes of the microvasculature result not only from damage to the capillaries themselves but also from changes of the perivascular structures.

Cisplatin-induced alterations in renal structure, ammoniagenesis and gluconeogenesis of rats.

Cisplatin [cis-diamminedichloroplatinum (II): CDDP] is a widely used cancer chemotherapeutic agent which has been shown to cause dose-related acute renal failure. The kidney damage is histologically characterized by widespread tubular necrosis, predominantly found in the third segments (S3) of the proximal tubules. To identify the intranephron targets of CDDP more precisely, we examined alterations in ammoniagenesis (AMG) and gluconeogenesis (GLG) using rat kidney slices (for AMG and GLG), tubule suspensions (for GLG), and microdissected nephron segments (for AMG). Ultramicroassay of AMG was carried out using the enzymatic cycling method, and GLG was measured by the HK/G6PHD method. GLG obtained from kidney slices and tubule suspensions on day 3 and day 7 following CDDP treatment did not change significantly from levels in control rats. In contrast, AMG increased on day 3 in the first and third kidney slices cut from the surface inward and decreased significantly on day 7 in the third and fourth slices. Microdissected nephron segments examined on day 7 showed decreased AMG in the second segments (S2; 20.3 +/- 7.7 pmol/mm/15 min vs. 78.7 +/- 9.7 for control, P less than 0.005) and the third segments (S3; 26.3 +/- 14.4 pmol/mm/15 min vs. 79.2 +/- 7.8 for control, P less than 0.005) of the proximal tubules. Additionally, we observed morphological changes under light microscopy to examine the relationship between metabolism and morphology. On day 3 following the CDDP treatment, typical acute tubular necrosis was seen primarily localized in the outer stripe of the outer medulla, while on day 7 the lesion appeared to be recovering. Our data imply a prominent dissociation between renal metabolic and morphologic changes induced by CDDP.

Adjuvant chemotherapy with vinblastine, adriamycin, and UFT for renal-cell carcinoma.

VAU therapy (vinblastine, Adriamycin, and UFT) was given postoperatively to 31 patients with stage I, II, or III renal-cell carcinoma, and the incidence of relapse as well as the survival of patients were studied. Administration was started at 7-14 days post-surgery; 5 mg/m2 vinblastine and 30 mg/m2 Adriamycin were given i.v. once every 4 weeks for a total of five courses, and three capsules of UFT (containing 300 mg tegafur) were given p.o. every day for 2-3 years. The postoperative observation period ranged from 2 years and 6 months to 7 years and 1 month (mean, 4 years and 2 months). The 1-year survival of patients was 100%, and the 3- and 5-year survival values were 96%. These results were significantly better (P less than 0.01) than the respective values (81%, 72%, and 60%) obtained for the historical controls, i.e., the 60 patients with stage I, II, or III renal-cell carcinoma who received no chemotherapy. Side effects such as alopecia, gastrointestinal symptoms, and myelosuppression were encountered, but all symptoms were so mild and transient that discontinuation of the treatment was not necessary. As VAU therapy might be useful as adjuvant chemotherapy for renal-cell carcinoma, it seems to merit further study.

[A case of priapism successfully managed by local irradiation].

A 42-year-old man with priapism is reported. The condition did not improve by cavernous body irrigation with heparin, intravenous administration of anticoagulant, or various surgical shunt operations. However, the condition improved after local radiation therapy: a total dose of 6Gy, 1.5 Gy daily for 4 days, was given to a site 24 cm x 24 cm which covered the small pelvic cavity and the femoral area centering around the root of the penis. Improvement of the condition became evident from Day 3 of radiation therapy. For about 1 year since then the patient has been entirely free of recurrence.

[Adjuvant chemotherapy with vinblastine, adriamycin and UFT (VAU) for renal cell carcinoma].

We tried adjuvant chemotherapy with vinblastine, adriamycin, and UFT on thirty-one renal cell carcinoma patients in stage I, II or III to determine whether or not it might improve their survival rate. The patients were started on adjuvant chemotherapy with vinblastine 5 mg/m2 i.v. and adriamycin 30/m2 i.v. 7 to 14 days after surgery, and drugs were administered every 4 weeks for a total of 5 times. UFT was administered orally in a dose of 3 capsules (300 mg as tegafur) daily for 2 to 3 years. The postoperative period averaged 4 years and 2 months with a range of 2 years and 6 months to 7 years and 1 month. The 1-year survival rate for the 31 patients was 100%, and 3- and 5-year survival rates were 96%. These results were encouraging, compared to the 1-, 3-, and 5-year survival rates of 81%, 72% and 60% achieved in a series of 60 renal cell carcinoma patients in stage I, II or III without adjuvant chemotherapy. Side effects such as alopecia, gastrointestinal symptoms, and myelosuppression were observed, but all symptoms were so mild or transient that the treatment could be continued in the patients.

Surgical approach to arteriovenous malformation of the medial temporal lobe--report of three cases.

We report three cases of arteriovenous malformation (AVM) of the medial temporal lobe and the surgical approaches used. The AVM was fed by the anterior choroidal artery (AChA) in two cases (Cases 1 and 2) and by the posterior cerebral artery in one (Case 3). The trans-Sylvian approach was first used for cerebrospinal fluid aspiration to retract the brain in all cases, and for confirming the feeding arteries to prevent premature bleeding from the AVM in Cases 1 and 2. In Case 1, a corticotomy was then made in the fusiform gyrus via the subtemporal approach to avoid the development of speech disturbance and visual field defects, while in Cases 2 and 3, a cortical incision was made in the middle temporal gyrus because visual field defects were preoperatively present. Cases 1 and 2 achieved good recoveries, but Case 3 suffered postoperative speech disturbance and died of rebleeding from a recurrent AVM fed by the AChA 22 months after the operation. This AVM was not demonstrated on the postoperative angiograms. We emphasize the usefulness of the combination of trans-Sylvian and subtemporal approaches for this lesion, because the feeding arteries are easily identified and retraction of the temporal lobe is alleviated. A corticotomy in the fusiform gyrus is also recommended to avoid the development of not only visual field defects but also aphasia.

Vertigo caused by scalenus anterior compression of the subclavian artery: a report of two cases.

Two cases of vertigo with subclavian artery stenosis are presented. In both cases, the angiograms revealed left subclavian artery stenosis at the middle portion of the clavicle as well as kinked origin of the vertebral artery. After resection of the anterior scalene muscle, the stenosis and the vertigo resolved.