Ming-Tsun Chen

Intracavernous pressure as an experimental index in a rat model for the evaluation of penile erection

This report communicates our attempt to design a small animal model for the evaluation of penile erection, based on the pharmacological responses of cavernous tissues in the rat that resemble those of human subjects. Male adult Sprague-Dawley rats anesthetized with pentobarbital sodium were used in conjunction with papaverine and prostaglandin E1, two vasoactive drugs most commonly used in clinical management of impotence. Intracavernous administration of papaverine (0.05, 0.1, 0.02, 0.4 or 0.8 mg.) induced a progressive increase in intracavernous pressure that peaked at 0.4 mg. This effect was associated with visible penile erection that became conspicuous when accompanied by additional bursts of transient intracavernous pressure fluctuations. The duration of papaverine-induced increase in intracavernous pressure was significantly shortened by clonidine (15 micrograms, intracavernous). Injection of prostaglandin E1 (1, 2 or 4 micrograms) into the corpus cavernosum also elicited an elevation in intracavernous pressure, but the responses exhibited acute tachyphylaxis. By manifesting a response to papaverine and prostaglandin E1 that is similar to that in human, we conclude that the intracavernous pressure in the rat may represent a suitable index for the evaluation of penile erection in small laboratory animals.

Elicitation of penile erection following activation of the hippocampal formation in the rat

We explore the possible involvement of the hippocampal formation in penile erection, using male, adult Sprague-Dawley rats that were anesthetized with pentobarbital sodium. The intracavernous pressure (ICP) was used as the experimental index for penile erection. Electrical activation of the hippocampal formation resulted in two patterns, viz, multiple and single episodes of elevation in ICP, along with visible penile erection and ejaculation. The former pattern exhibited an increase in ICP that was more sustained, with higher peak amplitude and longer latency. Furthermore, they originated respectively from the granule cells of the dentate gyrus and pyramidal cells of the CA1 and CA3 fields of the Ammons horn. Chemical stimulation of the hippocampus with glutamate also elicited significant increase in ICP. These results thus provided direct evidence to establish that the hippocampal formation may be involved in central neural regulation of the erectile process.

Decreased blood flow and defective energy metabolism in the varicocele-bearing testicles of rats.

This study was designed to elucidate the hemodynamic and energetic changes of testicles in experimental varicocele. Partial ligation of the left renal vein was performed in 10 Sprague-Dawley rats to induce dilatation of the internal spermatic vein, and sham operation was performed in the other 10 age-matched Sprague-Dawley rats used as controls. Blood pressure and rectal temperature were maintained at a constant level. Testicular blood flow was detected by laser Doppler flowmeter on the day before surgery and 4 weeks after surgery, respectively. Concentrations of various adenine nucleotides were determined by high-performance liquid chromatography (HPLC). We found a significant decrease from 10.2 +/- 1.5 to 7.4 +/- 1.8 mlLD/min/100 g (p < 0.005) in testicular blood flow after inducing varicocele in the rats. The energy charge of adenine nucleotides of the varicocele-bearing rats was 0.62 +/- 0.07 which was significantly lower than the 0.73 +/- 0.02 of the control group (p < 0.005). These observations have, thus, led us to propose the hypothesis that impaired spermatogenesis may result from defective energy metabolism in the varicocele-bearing testicles of rats.

Defective mitochondrial oxidative phosphorylation in varicocele-bearinc testicles

OBJECTIVESnOur previous study revealed a decreased blood flow in varicocele-bearing testicles. For further understanding of the possible mechanism of varicocele-induced infertility, we investigated the changes in energy metabolism in varicocele-bearing testicles.nnnMETHODSnPartial ligation of the left renal vein was performed in 40 Wistar rats to induce dilation of the internal spermatic vein, and sham operations were performed in 20 other age-matched Wistar rats serving as controls. Orchiectomy was done at 1, 2, 4, and 6 months after induction of varicocele (or sham operation) in both groups. The histologic changes in the testicles were evaluated under the light microscope. The concentration of adenine nucleotides was determined by high-performance liquid chromatography, and various enzyme activities of mitochondria were determined by a spectrophotometer.nnnRESULTSnHistologic studies of varicocele-bearing testicles showed a lower Johnsen score (8.5 +/- 0.7 versus 9.3 +/- 0.5) and a decreased mean testicular tubular diameter (280.0 +/- 3.2 versus 295.0 +/- 1.4 microns) compared with the testicles in the sham-operated group. The energy charge decreased from 0.71 +/- 0.04, 0.70 +/- 0.03, 0.69 +/- 0.06, and 0.64 +/- 0.03 to 0.62 +/- 0.08, 0.59 +/- 0.05, 0.58 +/- 0.05, and 0.56 +/- 0.02 at 1, 2, 4, and 6 months, respectively. The reduced nicotinamide-adenine dinucleotide-cytochrome c reductase activities were decreased from 136.6 +/- 4.9, 127.3 +/- 10.7, 121.6 +/- 7.8, and 118.9 +/- 8.5 to 96.3 +/- 13.9, 95.6 +/- 27.8, 88.3 +/- 13.8, and 80.4 +/- 8.7 nmol/min/mg of protein, respectively; the succinate-cytochrome c reductase activities were decreased from 50.4 +/- 2.7, 49.0 +/- 4.7, 49.6 +/- 7.1, and 42.6 +/- 1.6 to 40.3 +/- 7.3, 41.0 +/- 11.5, 40.2 +/- 5.7, and 32.0 +/- 1.3 nmol/min/mg of protein, respectively; and the cytochrome c oxidase activities were decreased from 361.2 +/- 23.4, 350.3 +/- 25.5, 223.5 +/- 12.9, and 194.1 +/- 18.3 to 253.7 +/- 32.9, 256.4 +/- 38.8, 178.2 +/- 15.7, and 147.1 +/- 17.2 nmol/min/mg of protein at 1, 2, 4, and 6 months, respectively.nnnCONCLUSIONSnWe thus suggest that defective energy metabolism plays an important role in the impairment of spermatogenesis of varicocele-bearing testicles.

PARANEOPLASTIC ELEVATION OF SERUM ALKALINE PHOSPHATASE IN RENAL CELL CARCINOMA: INCIDENCE AND IMPLICATION ON PROGNOSIS

PURPOSEnWe investigated the incidence and prognostic significance of paraneoplastic elevation of serum alkaline phosphatase in patients with renal cell carcinoma.nnnMATERIALS AND METHODSnClinical data of 365 pathologically proved renal cell carcinoma cases were reviewed. Serum alkaline phosphatase level greater than 100 units per 1., but without obvious conditions that may cause phosphatase elevation, including metastasis to or disease of liver or bone and pregnancy, was regarded as paraneoplastic serum alkaline phosphatase elevation. Survival was evaluated using the Kaplan-Meier method.nnnRESULTSnOf 365 patients 77 (21.1%) had paraneoplastic serum alkaline phosphatase elevation. The respective incidence from stage I to IV cases was 9.9% (16 of 161), 31.9% (15 of 47), 34.3% (23 of 67) and 25.6% (23 of 90). Patients with stage I disease had the lowest incidence but there were no statistically significant differences among stages II, III and IV disease. Of 77 patients with elevated serum alkaline phosphatase 48 had additional paraneoplastic manifestations. The disease specific 5-year survival rate in patients with normal serum alkaline phosphatase was significantly better than in patients with isolated phosphatase elevation, which in turn was better than in patients with multiple paraneoplastic syndromes (70.7 versus 50.5 versus 30.8%). Patients with persistent or recurrent elevation of serum alkaline phosphatase after radical nephrectomy had metastatic lesion or local recurrence. In some patients serum alkaline phosphatase returned to normal after nephrectomy but metastasis developed later without recurrent phosphatase elevation.nnnCONCLUSIONSnParaneoplastic serum alkaline phosphatase elevation in renal cell carcinoma patients implies an unfavorable prognosis, and additional paraneoplastic syndromes further worsen the prognosis. Recurrent or persistent serum alkaline phosphatase elevation after radical nephrectomy suggests distant metastasis or residual tumor. However, the return of serum alkaline phosphatase to normal does not guarantee cure of the disease. Identification of paraneoplastic serum alkaline phosphatase elevation is valuable in the prediction of outcome and postoperative followup of renal cell carcinoma patients.

Correlation of Contractile Function and Passive Properties of Rabbit Urinary Bladder Subjected to Outlet Obstruction—An in Vitro Whole Bladder Study

The present study investigated the correlation between contractile function and passive properties of rabbit urinary bladder subjected to outlet obstruction. Mild bladder outlet obstruction was induced by placing silicone rings (7 mm. diameter) around the bladder necks of male New Zealand rabbits. The animals were sacrificed after 2 weeks of obstruction. Contractile function was evaluated by measuring the response of the in vitro whole bladder to 500 microM bethanechol administration. Passive properties was assessed by performing in vitro cystometry and stress-relaxation techniques utilizing six different infusion rates. When the intravesical pressure reached 30 cm. H2O the infusion was stopped, allowing the bladder to relax and intravesical pressure to drop to a steady state level. The results can be summarized as follows: 1) Although the intravesical pressure response to bethanechol was about the same in control (13.3 cm. H2O) and obstructed (12.4 cm. H2O) bladder, the obstructed bladder emptied significantly less than control (20.4 vs 89.3%); 2) the results of the passive properties study showed that bladder stiffness was significantly higher at all infusion rates in the obstructed bladder, 3) the obstructed bladder showed significantly less relaxation after rapid stretching of the whole bladder by high speed fluid infusion; 4) histological examination of obstructed bladders revealed marked fibrous thickening of the serosal layer, interstitial fibrosis of the muscle layers, and hypertrophic and/or degenerative changes of the muscle fibers. In summary, 2 weeks after mild outlet obstruction of the urinary bladder the emptying ability, but not pressure generation, was reduced along with increased bladder stiffness and diminished capacity for stress-relaxation. Interstitial fibrosis and changing the properties of the smooth muscle cells might be involved in the functional impairment and deranged viscoelasticity of the urinary bladder after outlet obstruction.

Urodynamic and Clinical Outcome of Kock Pouch Continent Urinary Diversion

Urodynamic studies of the Kock pouch were conducted in 20 patients 3 to 36 months after radical cystectomy and urinary diversion for invasive bladder cancer. Functional pouch capacity, intrapouch pressure, maximal nipple pressure, maximal nipple closure pressure and functional nipple length with the pouch filled to capacity were measured. Intermittent involuntary pressure spikes resembling bowel peristaltic waves occurred in 5 patients (25 per cent). The mean functional pouch capacity was 280.0 +/- 119.2 ml. (standard deviation) and mean maximal intra-pouch pressure was 41.0 +/- 11.0 cm. water in patients with involuntary pressure spikes. In patients without involuntary pressure spikes these values were 332.7 +/- 114.5 ml. and 11.6 +/- 4.8 cm. water, respectively. For all patients the mean maximal nipple pressure was 72.1 +/- 24.6 cm. water, the mean maximal nipple closure pressure was 58.8 +/- 23.1 cm. water and the mean functional nipple length was 3.4 +/- 0.9 cm. A functional nipple length of less than or equal to 2.5 cm. and/or a low maximal nipple closure pressure (less than 40 cm. water) correlated with a small functional pouch capacity (less than 200 ml.) in 5 patients. Clinically, these 5 patients also required frequent catheterization to provide continence. A maximal nipple closure pressure greater than 60 cm. water and an adequate functional nipple length (greater than 3.0 cm.) correlated with a rather large functional pouch capacity (more than 350 ml.). The degree of continence provided by the Kock pouch appeared to be determined by functional nipple length, maximal nipple closure pressure, functional pouch capacity and maximal intrapouch pressure.

Adrenal cortical carcinoma with tumor thrombus invasion of inferior vena cava

A case of adrenal cortical carcinoma with inferior vena cava (IVC) involvement is presented. Ultrasonography, computed tomography, and venacavography all presumptively showed a large mass over the upper pole of the left kidney with tumor thrombus in the IVC. However, aortography demonstrated that this mass was receiving its blood supply from the left inferior phrenic artery, aorta, and left renal artery. Radical surgery, including resection of the tumor and its adjacent organs (kidney, distal pancreas, spleen) and the tumor thrombus in the IVC, with the aid of cardiopulmonary bypass, was performed. We emphasize that adrenal cortical carcinoma can have tumor thrombi invading the IVC, and in such cases we suggest radical surgical removal of the tumor and the thrombus.

Incidental adenocarcinoma of the prostate : a retrospective analysis

Between January 1980 and June 1990, 5875 patients underwent either TURP (5,529) or open prostatectomy (346) for the management of benign prostatic hyperplasia. Incidental carcinoma was identified in 53 patients (0.9%) - 49 in the TURP group and 4 in the open prostatectomy group. The overall incidence of stage A prostate carcinoma during the same period was 13.1% (53/406). Of those 50 regularly followed patients, only 6 (12.0%) underwent subsequent radical prostatectomy with pelvic lymphadenectomy, and residual tumors were identified in 4 patients (66.7%). The progression rate was 33.3% (3/9) in high-grade tumors (Gleasons score greater than 6) and 7.7% (2/26) in low-grade tumors (Gleasons score less than 5). In those 50 patients, 41 (82.0%) presented no evidence of disease and 9 (18.0%) stayed alive with progression. The mean length of follow-up was 34 months (range: 2-108 months). Our study demonstrates that the outcome of incidental carcinoma of the prostate is good. However, the residual tumor rate still remains high at 66.7%. Radical prostatectomy is recommended in young patients or in patients with high grade tumor.

Cisplatin-based chemotherapy for the treatment of advanced transitional-cell carcinoma of the urinary tract — a preliminary report

SummaryThe CMV (cisplatin, methotrexate, and vinblastine) and M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimens were used to treat 19 patients with advanced transitional-cell carcinoma (TCC) of the urothelial tract. In the CMV group, the partial response rate was 45.5% and the mean response duration was 6.3 months. No complete response was obtained in our series. The median duration of survival was 15.8 and 8.3 months in responders and nonresponders, respectively. The toxic symptoms included one case of sepsis and three cases of renal toxicity. However, nausea and vomiting were experienced by most patients and required the administration of antiemetics. In the M-VAC group, the median duration of survival for responders was longer than that of nonresponders (>10.2 vs 7.2 months), although the number of patients was too small for this difference to reach statistical significance. The toxic symptoms included one case of sepsis, two cases of renal toxicity, and nausea and vomiting in most patients. Bone metastasis in three patients did not respond to chemotherapy (CMV), a finding that is compatible with the results reported by other investigators. In summary, chemotherapy with the CMV or M-VAC regimen was effective in improving the response rate of patients. However, the duration of response was short, toxicity was severe in some cases, and the efficacy against bone lesions was poor. These problems must be solved to improve the outcome of patients with TCC following chemotherapy with the CMV or M-VAC regimens.