Nephrotoxicity of high- and low-osmolar contrast media. The protective role of amlodipine in a rat model.

PURPOSE: To evaluate the nephrotoxicity of high- and low-osmolar contrast media (HOCM, LOCM) on kidneys in Sprague-Dawley rats. The protective role of amlodipine was studied. MATERIAL AND METHODS: Forty rats of both sexes were randomly divided into 5 groups (n=8/group) and glycerine for inducing renal failure was given to all rats except controls. RESULTS: In diatrizoate-injected rats, blood urea nitrogen (BUN) and serum creatinine (SCr) were increased; levels of phospholipase A2 (PLA2), lipid peroxide (LPO) and calcium were also increased in renal tissues. There was no significant difference between LOCM (iohexol) animals and glycerol controls either in the renal levels of PLA2, LPO and calcium or in the levels of BUN and SCr. The histologic changes were milder in the LOCM animals than in the HOCM animals. In the group pretreated with amlodipine, no increase in the levels of BUN or SCr was discovered and the renal content of PLA2, LPO and calcium were significantly lower than in the HOCM group; the renal injuries induced by diatrizoate were alleviated. CONCLUSION: The HOCM, diatrizoate, was more toxic to rat kidneys than the LOCM iohexol; PLA2, LPO and calcium load played a role in producing renal function impairment induced by diatrizoate meglumine; amlodipine protected the renal tissue from nephrotoxicity induced by diatrizoate.

Assessment of urinary endothelin-1 and nitric oxide levels and their relationship with clinical and pathologic types in primary glomerulonephritis.

To determine the relationship between the urinary endothelin (ET-1), nitric oxide (NO) levels and the clinical, pathologic types of primary glomerulonephritis (GN) patients, urinary levels of ET-1 and NO were detected in 27 patients with biopsy-proven primary GN and 12 normal controls by radioimmunoassay and by copper-plated and cadmium column reduction assay, respectively. The results showed that urinary ET-1 levels in the patients with primary GN were significantly higher than in normal controls (p < 0.01), while the urinary ET-1 levels in patients with moderate mesangial proliferation GN were significantly higher than those in patients with mild mesangial proliferation GN (p < 0.05). Urinary ET-1 levels in patients whose clinical feature was nephrotic syndrome were found to be higher than in patients whose clinical feature was nephritic syndrome. However, urinary NO levels were to the contrary (p < 0.05). The ratio of ET-1/NO in primary GN patients was significantly higher than that in normal controls, and it positively correlated with the 24-hour urinary excretion of protein. These results suggest that urinary ET-1 levels are related to the proliferation of mesangial cells. The imbalance between ET-1 and NO may be related to the pathogenesis of primary GN and the occurrence of proteinuria.

Assessment of renal function in the early stages of nephrotoxicity induced by iodinated contrast media.

To determine whether there are early renal function parameters (RFP) which can be monitored to rapidly detect nephrotoxicity induced by contrast media (CM), we observed RFP in 16 patients with normal renal function before and after administration of CM. Forty-eight hours after diatrizoate meglumine administration, blood urea nitrogen (BUN) and serum creatinine (SCr) increased (p < 0.05). In all patients, acute tubular damage was revealed by early urinary RFP. Increases in levels of serum angiotensin-I-converting enzyme (ACE), beta(2)-microglobulin (beta(2)M) and urinary albumin (Alb) were associated with alterations in glomerular function. The changes in early RFP occurred earlier than those of BUN and SCr. The present study demonstrates that serum ACE, beta(2)M, urinary Alb, gamma-glutamyl-transpeptidase and N-acetyl-beta-D-glucosidase are sensitive parameters for the early assessment of subclinical nephrotoxicity induced by CM.

[Changes of early renal function before and after using mannitol in patients with cerebral apoplexy].

The alteration of renal function after initiation of mannitol infusion were monitored in 20 patients with cerebrovascular accident to evaluate whether mannitol has nephrotoxicity effects. Serum creatinine and urea nitrogen were increased after initiation of mannitol infusion, but hadn't reached stagistical significance. Urinary and serum alpha 1-microglobulin, beta 2-microglobulin and urinary NAG, gamma-GT were significantly increased after 5-10 days successive infusion of mannitol (P < 0.05). The results suggest that the acute nephrotoxicity effect of mannitol should not be ignored.

Assessment of in situ renal transplant viability by 31P-MRS: experimental study in canines.

In 14 in situ canine renal transplants, intracellular phosphorus metabolites were evaluated by phosphorus-31 magnetic resonance spectroscopy (31P-MRS), performed using surface coils to investigate the usefulness of this technique for assessing renal viability in situ. Group I control kidneys (n = 5) were autografts, as were Group II (n = 5) kidneys: the latter group were subjected to surgically induced vascular ischemia and thrombosis. Group III kidneys (n = 4) were rejecting allografts. Renal flow and function, as measured by 99mTc-DTPA, and findings on histologic examination were correlated with 31P-MRS spectra. Group I kidneys showed excellent viability on both 99mTc-DTPA studies and biopsy evaluation, and their 31P-MRS-derived ratios of phosphomonoesters/inorganic phosphate (PME/Pi) and adenosine triphosphate/Pi (ATP/Pi) were high (1.32 +/- 0.23 and 0.90 +/- 0.36, respectively). In contrast, Group II kidneys demonstrated poor flow and function, histologic evidence of severe ischemia from venous and arterial thrombosis, and significantly (P < 0.005) less viability than controls, as monitored by 31P-MRS PME/Pi (0.58 +/- 0.30) and ATP/Pi (0.20 +/- 0.13) ratios. Group III kidneys also demonstrated poor flow and function with 99mTc-DTPA, and the associated histologically injury was noted to be caused by accelerated rejection and severe vascular damage. PME/Pi (0.24 +/- 0.22) and ATP/Pi (0.10 +/- 0.01) ratios were also significantly (P < 0.005) less than those in controls, reflecting nonviability. The 31P-MRS-derived PME/Pi and ATP/Pi ratios enable a qualitative noninvasive assessment of blood flow-dependent renal viability, but with currently used localization techniques the differentiation between severe ischemia and severe acute rejection was not possible.

[Therapeutic effects of Chinese drugs on early renal damage of rats caused by fish bile].

The therapeutic effects of Salvia miltiorrhizae, Typha angustifolia, Rheum palmatum preparations on early renal damage of rats caused by fish bile were observed. These drugs were effective in reducing serum creatinine, urinary NAGase, count of necrosed epithelial cells of proximal tubule and that of glomerular filled with RBC in Bowman's space (P < 0.05), and also effective in increasing creatinine clearance (P < 0.05).

Chronic papaverine treatment: the effect of repeated injections on the simian erectile response and penile tissue.

To investigate the effect of chronic papaverine treatment, seven monkeys underwent repeated intracavernous injections for one year. One monkey died after 56 injections; the others received a total of 100 each. The strength and duration of erection were recorded after each injection, and the erectile tissue was examined histologically at the end of the study. Over the long term, papaverine maintains its erection-inducing capability, but it does cause pathologic changes in the erectile tissue: minimal to marked fibrosis at the injection site and hypertrophy of smooth muscle in the non-injected area of the corpus.

The role of vasoactive intestinal polypeptide as a neurotransmitter in canine penile erection: a combined in vivo and immunohistochemical study.

Vasoactive intestinal polypeptide (VIP), a 28-amino-acid polypeptide found in the human gut and genitourinary tract, primarily affects vasodilation and smooth-muscle relaxation. These effects have led to speculation that this neuropeptide may be a neurotransmitter in certain bodily functions, such as penile erection. We therefore designed an in vivo animal model to elucidate the influence of VIP and VIP antibody on the different stages of penile erection. We also performed immunohistochemical studies of the penile tissue to obtain further information about the distribution of VIP in the corpora cavernosa. Intracavernous injection of VIP induced penile erection. Its effect on arterial inflow was minor, but it caused active venous outflow restriction and was important in maintaining erection. VIP antibody blocked venous outflow restriction during neurostimulation-induced erection. VIP was found in the cavernous tissue (in the area between the smooth-muscle cells and the sinusoidal spaces) in close proximity to the arteries. We conclude that VIP is a neurotransmitter in the erectile tissue of the penis, and that its effects are similar to those from electrostimulation of the cavernous nerve. VIP increases arterial flow, decreases venous flow, and induces sinusoidal relaxation.

The effect of cigarette smoking on penile erection.

Clinical observations suggest that cigarette smoking impairs erectile function in patients with moderate arterial insufficiency. To evaluate the effects of smoking on the physiology of erection, we studied six healthy adult mongrel dogs in which bipolar cuff electrodes were implanted around the cavernous nerves. After threshold stimulation parameters for penile erection were established, cigarette smoke collected in a 60-ml. syringe was released slowly near the dog's mouth, to be inhaled by natural breathing. Stimulation of the cavernous nerve was repeated and blood samples for nicotine, cotinine and blood gases were obtained before and after each cigarette. The systolic and intracorporeal pressure, flow through the internal pudendal artery, and venous flow from the corpora cavernosa were recorded at baseline and with each electrostimulation after smoke inhalation. Five of the six dogs were unable to achieve full erection after inhalation of smoke from two to three cigarettes. Some decrease of flow through the internal pudendal artery occurred and the venous restriction ability was almost completely abolished by smoking. Further, when nicotine was injected intravenously into two additional dogs, the same phenomenon was observed. These findings support the idea that cigarette smoking may contribute to impotence in some patients.

Priapism induced by chlorpromazine and trazodone: mechanism of action.

To investigate the mechanism of drug-induced priapism, we gave the antipsychotic agent chlorpromazine and the antidepressant trazodone to 14 dogs by intravenous and intracorporeal injection. Bilateral intracorporeal pressure, blood flow within the internal pudendal artery, and systemic blood pressure were monitored. Venous outflow restriction was evaluated by continuous saline infusion of the corpus cavernosum with the infrarenal aorta clamped. When delivered by intracorporeal injection, both drugs induced erection in a manner similar to that of intracorporeal injection of papaverine. Internal pudendal arterial flow increased slightly at the beginning of tumescence, and excellent venous restriction occurred. Intravenous injection, however, could neither induce an erection nor facilitate an erection after sub-threshold neurostimulation. We believe that the alpha-adrenergic antagonist properties of chlorpromazine and trazodone probably cause priapism by local action.

Further evidence of venous outflow restriction during erection.

To elucidate the effect of venous outflow restriction during erection, we studied eight dogs during artificial saline perfusion of the penis with and without neurostimulation to induce erection. With the infrarenal aorta clamped temporarily, saline infusion rates of 0.9 and 1.9 ml/min raised the mean intracorporeal pressure to 34 and 42 cm H2O, respectively, before stabilisation or return to baseline. When cavernous nerve stimulation was initiated, the mean intracorporeal pressure rose to 124 and 184 cm H2O (with infusion rates of 0.9 and 1.9 ml/min respectively) to induce full erection. Our results show that venous outflow restriction takes place during erection and that it is necessary not only to induce full erection but also to maintain it. Evaluation of venous competence is therefore essential during the investigation of impotence.

[Thymoma--report of 268 cases].

This paper reports 268 cases of thymoma treated by surgery and followed up to 24 years in our hospital. We believe that thymoma is a low grade malignancy. The gross findings on thoracotomy and microscopic examination are useful for diagnosis. The prognosis is related to the morphology of the tumor capsule. For patients with noninvasive thymoma, the prognosis is excellent and the recurrence rate is the lowest. In spite of a benign histologic feature, the prognosis is poor for patients with invasive thymoma which gave a 5 and 10 year survival rate of 65.5% and 48.8%, respectively with a recrudescence rate of 41.0%. Surgery is strongly indicated for thymomas. Invasive thymoma must be excised as early as possible. Extensive and thorough resection is the best way of preventing recurrence. The recurrent or metastatic foci can also be resected and cured by surgery. The survival time may be prolonged by radiotherapy. The residual tumor tissue can be effectively controlled by postoperative irradiation. The recurrent tumor may also be cured by radiation. Yet the result of patients with intrapleural seeding is not improved by postoperative radiation.