Long-term vardenafil therapy improves hemodynamics in patients with pulmonary hypertension.

The phosphodiesterase-5 (PDE-5) inhibitor, sildenafil, has been reported to produce sustained pulmonary vasodilatation in patients with pulmonary hypertension (PH). Recently, vardenafil, a more potent and selective PDE-5 inhibitor than sildenafil, has been approved for the treatment of erectile dysfunction. However, the long-term effects of oral vardenafil in patients with PH are unknown. We studied five consecutive patients with PH; one with primary pulmonary hypertension, two with chronic pulmonary thromboembolism, one with Eisenmenger syndrome (ventricular septal defect) and one with secondary pulmonary hypertension after a ventricular septal defect closure operation. In an acute hemodynamic trial, vardenafil (5 mg) significantly decreased both the pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) with an increase in cardiac output. In a chronic hemodynamic trial, the maintenance dose of vardenafil (10 to 15 mg) for 3 months significantly decreased the PVR, but not the SVR, with a 20.7% reduction of the PVR/ SVR ratio. Plasma brain natriuretic peptide (BNP) levels were also significantly decreased after 3 months. This pilot study demonstrates that long-term oral vardenafil therapy may be a safe and effective treatment for patients with PH.     

Cerivastatin inhibits fetal calf serunvinduced DNA synthesis in cultured rat mesangial cells

SUMMARY: Inhibition of mevalonate synthesis by several statins has been shown to suppress DNA synthesis in glomerular mesangial cells. In the present study, we investigated the effect of a new statin, cerivastatin, on fetal calf serum (FCS)-induced DNA synthesis of cultured rat mesangial cells. Cultured rat mesangial cells were stimulated by 10% FCS in the presence or absence of cerivastatin and mevalonate. 5-bromo-2-deoxyuridine (BrdU) incorporation was used to assess DNA synthesis. the present study showed that 10% FCS caused marked stimulation of DNA synthesis in the mesangial cells. Cerivastatin inhibited FCS-stimulated BrdU incorporation in a dose-dependent manner. IC₅₀ was approximately 1 umol/L. Exogenous mevalonate, farnesyl pyrophosphate and geranylgeranyl pyrophosphate significantly prevented the inhibitory effect of cerivastatin on DNA replication. It appears that cerivastatin, by inhibiting the synthesis of mevalonate, may suppress DNA synthesis in the mesangial cells.     

Colonic pseudolipomatosis, microscopically classified into two groups

Background: Colonic pseudolipomatosis is rare and the pathogenesis is controversial. The purpose of the present paper was to clarify endoscopic and histological characteristics of colonic pseudolipomatosis and to discuss the etiology. Methods: A total of 15 lesions from 14 patients was reviewed. They were able to be histologically classified into two groups on the basis of variety in size of the vacuoles: Group A, the ratio of largest vacuole to smallest vacuole in size is less than three, Group B, the ratio is more than four. Results: Four of 15 lesions were group A, and were endoscopically polypoid or flat lesions covered with normal‐looking mucosa. They were microscopically characterized by (i) predominant location in the upper portion of the lamina propria; (ii) no submucosal involvement; (iii) less variation in vacuolar size; and (iv) no association with lymph follicles. The vacuoles of group A contained proteinaceous materials in two of four lesions. Group B (11 lesions) had small elevated mucosa with normal‐looking surface or non‐elevated reddish mucosa. Microscopically, the lesions were mainly located in the lower portion of the lamina propria, occasionally also in the submucosa, had variable‐sized vacuoles, and were related to lymph follicles. Conclusion: It is suggested that the vacuoles in group A contain fluid, and may indicate an abnormal stagnation of interstitial fluid. Microscopic appearance of group B is essentially similar to that of pneumatosis coli. It is thought that group B probably results from penetration of gas from the crypts into the mucosa during colonoscopy. It is unclear why group B had a preference for ileocecal valve and an association with lymph follicles.     

Surgical exploration for renal cyst: two-case report]

A 59-year-old male was admitted to our clinic for further examination of the calcified renal cyst discovered incidentally on medical workup elsewhere. CT showed a left renal cyst associated with calcification. Ultrasound-guided puncture of the renal cyst was not successful because of thickness of the cystic wall. Renal angiography showed hypervascularity of the cystic wall. Association of renal cell carcinoma could not be ruled out, therefore the exploration was performed. Histological examination revealed benign renal cyst with calcification. A 27-year-old male presented with the chief complaint of left flank pain. Following examinations by US, CT and MRI, a renal cyst associated with renal cell carcinoma was highly suspected. Subsequent exploration revealed cluster of cysts with a yellowish lesion a few mm in diameter. Frozen section revealed no malignancy, and cystic fluid was not hemorrhagic. Therefore as many cystic walls as possible were removed without nephrectomy. Histological examination of the permanent specimen revealed renal cell carcinoma. Renal cyst associated with renal cell carcinoma was regarded as rare clinical entity, but such cases are reported in increasing number in recent years. We report such cases and review the pertinent literature in this paper.     

Ouabain as an amplifier of mineralocorticoid-induced hypertension.

Ouabain has recently been reported to be an endogenous Na, K-ATPase inhibitor. To evaluate whether it exerts hypertensive action itself or amplifies the hypertensive action of small doses of mineralocorticoids, 5 mg deoxycorticosterone acetate (DOCA), 1 mg ouabain, or a combination of both were injected into mononephrectomized rats weekly for 6 weeks, and changes in blood pressure were evaluated. The blood pressures of control, DOCA-treated, ouabain-treated, and the combination treatment group at the sixth week were 138 +/- 3 (SE), 160 +/- 6, 144 +/- 6, and 201 +/- 14 mmHg, respectively. The blood pressure of rats given DOCA or ouabain alone was not significantly different from that of controls. In contrast, the blood pressure of rats given the combination of DOCA and ouabain was significantly higher than that of control rats and those given DOCA or ouabain separately. Cardionephromegaly and histopathological changes found in rats given the combination of DOCA and ouabain were consistent with the effects of an elevation of blood pressure. Further evaluation revealed that the amplification effect of ouabain on the hypertensive action of DOCA was dose dependent, with the minimum dose that caused the amplification effect being 0.25 mg/week. These results indicate that ouabain, although devoid of hypertensive action itself, amplifies the hypertensive action of small doses of DOCA and can cause a hypertensive state similar to that induced by larger doses of DOCA. It is inferred that the amplification effect of ouabain on mineralocorticoids is important in the genesis of hypertension.     

ALCOHOL-RELATED SUDDEN DEATH WITH HEPATIC FATTY METAMORPHOSIS: A COMPREHENSIVE CLINICOPATHOLOGICAL INQUIRY INTO ITS PATHOGENESIS

To clarify the pathogenesis of the widely known but obscuresyndrome of sudden death with hepatic fatty metamorphosis observedin alcohol abusers, we have scrutinized both the clinical andpathological data of 11 subjects who died under such circumstancesbetween 1987 and 1993. Death followed several days of uninterrupteddrinking often with little dietary intake. The notable clinicalfeatures on arrival at the emergency room were disturbance ofconsciousness (11/11), hypotension (47/6), hypothermia (3/5),hypoglycaemia (8/11), metabolic acidosis (6/6), renal dysfunction(11/11), and hyperammonaemia (5/5). The common hepatic pathologywas the extensive appearance of numerous microvesicular fattydroplets in the hepatocytes together with varying degrees ofmacrovesicular fatty change; four subjects had an underlyingcirrhosis. Death undoubtedly results from a variety of metabolicdisturbances triggered by the combination of massive ethanolintake and starvation. The appearance of extensive microvesicularfatty change superimposed on macrovesicular fatty change wasconsidered to be an associated phenomenon     

Retrograde endoscopic laser therapy for transitional cell carcinoma of the upper urinary tract

AIM: The aim of the present study was to investigate the safety and efficacy of endoscopic laser therapy for transitional cell carcinoma (TCC) of the upper urinary tract. METHODS: Tumors of the renal pelvis and ureteropelvic junction were detected by ureteroscopy. The tumors were subjected to biopsy, and after TCC was diagnosed, endoscopic laser therapy (Neodymium-YAG and Holmium-YAG) was conducted using a 6.9 Fr. flexible ureterorenoscope. RESULTS: From January 1997 to April 2002, six patients underwent ureteroscopic treatment. Tumor grade was 1 in four patients and 2 in two patients. Average tumor size was 1.45 cm. Endoscopic treatment was chosen for two patients because of the high medical risk associated with open surgery. Another patient underwent diagnostic ureteroscopy, followed immediately by endoscopic treatment. A further three patients elected to undergo ureteroscopic treatment. One patient with large (3 cm), multifocal and incompletely treated tumors died of metastatic disease 22 months after the initial operation. One patient requested nephroureterectomy one month after endoscopic treatment, and pathological examination of the resected specimen revealed no tumor. The other four patients have been followed up for a mean period of 14 months after initial treatment. Recurrence occurred in one patient, and was successfully treated by repeat endoscopic resection. None of the patients required blood transfusion or emergency open surgery. CONCLUSION: Ureteroscopic treatment of small, localized, low-grade TCC of the upper urinary tract is now a safe and feasible alternative to nephroureterectomy in selected patients.     

Intracellular vesicular stomatitis virus nucleocapsids and virions visualized by surface spreading

Spreading of cells on a solution surface could visualize vesicular stomatitis virus nucleocapsids and virions in infected cells easily and clearly without the need for any purification. Characteristic structures observed by the spreading of the infected cells are described and discussed.     

Effect of relaxation training on cardiac parasympathetic tone

To examine the hypothesis that the relaxation response is associated with an increase in cardiac parasympathetic tone, the frequency components of heart rate variability during relaxation training were investigated in 16 college students. Electrocardiograms and pneumograms were recorded during a 5-min baseline period followed by three successive 5-min sessions of the autogenic training (relaxation) or by the same periods of quiet rest (control), while subjects breathed synchronously with a visual pacemaker (0.25 Hz). Although neither the magnitude nor the frequeney of respiration showed a significant difference between relaxation and control, the amplitude of the high-frequency component of heart rate variability increased only during relaxation (p= .008). There was no significant difference in the ratio of the low-frequency (0.04–0.15 Hz) to the high-frequency amplitudes. The increased high-frequency amplitude without changes in the respiratory parameters indicates enhanced cardiac parasympathetic tone. Thus, our results support the initial hypothesis of this study. Enhanced cardiac parasympathetic tone may explain an important mechanism underlying the beneficial effect of the relaxation response.