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Biomedical subjects

K K Chen

Publications and source records attributed to K K Chen.

At least 19 recordsLinked to original sources

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 Ammon's 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.

Animals

Sonographic measurement of penile erectile volume.

For more accurate determination of the penile erectile volume in the flaccid and erectile states, and the difference between them, 20 impotent patients from 36 years old to 70 years old were enrolled in the study. Penile Doppler ultrasonography was performed to check the diameter of each corpus cavernosum, and diameter and peak flow velocity of each cavernous artery before and after intracavernous injection with 10 micrograms to 20 micrograms prostaglandin E1 (PGE1). The penile length was measured from base to midglans manually before and after PGE1 injection. The erectile volume in flaccid and erectile states was calculated as pi r2 x length. The summation of erectile volume of left and right corpus cavernosum was taken as the total erectile volume. The patients were classified into good (10 patients) and poor (10 patients) response groups based mainly on the mean peak flow velocity of both cavernous arteries greater or less than 25 cm/s. There was a significant increase of erectile parameters (penile length, diameter of corpus cavernosum, and total erectile volume) after PGE1 injection in each group of patients. For the total of 20 patients, the mean increase of penile length was 4.27 cm (80.0%), the diameter of corpus cavernosum was 0.66 cm (77.9%), and total erectile volume was 27.87 mL (459.0%). A comparison of the increase of penile erectile parameters after PGE1 injection between the good and poor response groups of patients revealed a significantly greater increase of the diameter of corpus cavernosum in the good response patients.

Adult

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

The 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 (greater than 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.

Adult

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.

Alprostadil

Diagnosis of venous leakage by 133Xe corporeal clearance after intracavernous injection of prostaglandin E1 in poorly responding patients.

133Xe corporeal clearance after intracavernous (IC) prostaglandin E1 (PGE-1) injection was assessed in detecting venous leakage (VL) in a group of impotent patients with poor clinical response to PGE-1 injection. 133Xe corporeal washouts were done in the flaccid state and at full erection or at 20 min after the IC injection of 20 micrograms PGE-1 in cases where no full erection occurred in sequence on two separate days. In each case, data were acquired in frame mode after intracorporeal injection on one side of the midline just behind the glans of 0.1 ml, namely, 1-2 mCi (34-74 MBq) 133Xe in saline for 20 min. A time-activity curve was generated from the region of interest (ROI) at the site of injection and a computer routine was used to calculate clearance half-time (T1/2) in min and flow rate (Q) in ml per 100 g tissue per min. The data of 20 patients with equivocal response to IC PGE-1 were analysed. Of them, 14 had venous leakage and six had no vascular impairment (NVI). Venous leakage was proved by Doppler analysis, cavernosography after PGE-1, and/or selective arteriography. Twelve of 14 patients with VL had enhanced 133Xe corporeal clearance after PGE-1 with a significant decrease in T1/2 (mean +/- S.D.) from 115.9 +/- 196.0 to 13.3 +/- 13.4 (P less than 0.05) and increase in Q from 2.1 +/- 2.2 to 7.5 +/- 5.6 (P less than 0.01). In contrast, all six patients with NVI had decreased 133Xe corporeal clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Construction of detubularized ileal neobladder after radical cystoprostatectomy.

In an attempt to improve the patient's quality of life, we performed construction of neobladder using detubularized ileum along with radical cystoprostatectomy in 3 male patients with invasive bladder cancer. The mean followup was 28.3 months (16-45 months). All 3 patients achieved continent urination through the natural urine pathway-urethra with a satisfactory urinary stream during the day, but only 2 of them could also obtain continence in the night. Urodynamic study of the ileal neobladder showed a low pressure (mean 15.3 cm water) and no involuntary pressure spikes in the neobladder. The maximal urethral closure pressure (mean 62.0 cm water) and functional profile length (mean 3.0 cm) were adequate. In addition, the maximal uroflow rate was good (mean 16.7 ml/sec). There was no reflux in any of our patients. The radionuclide renal function study revealed that the renal function was preserved after operation in all 3 patients. Neocystourethroscopy showed no tumor and no stricture at the ileourethral anastomotic site in our 3 patients. There was no complication related to the operation. No disturbances of nutrition or electrolytes were found in any patient. All 3 patients had a satisfactory quality of life after operation though one patient died of widespread metastasis 16 months after operation. In conclusion, construction of detubularized ileal neobladder may be one of the ideal surgical procedures for bladder substitution after radical cystoprostatectomy.

Aged

Radionuclide renal function study in various surgical treatments of upper urinary stones.

We conducted a radionuclide renal function study using 131I-hippuran in 188 patients with upper urinary stones before and every 3 months to the maximum of 12 months after various surgical treatments. Of 28 patients with renal staghorn stone, 24 underwent anatrophic nephrolithotomy and 4 percutaneous nephrolithotomy (PCNL). Of 36 patients with renal pelvic stone, 15 received open pyelolithotomy, 16 received PCNL and 5 received extracorporeal shock wave lithotripsy (ESWL). Of 71 patients with renal calyceal stone, 48 underwent PCNL and 23 ESWL. Of 53 patients with ureteral stone, 41 received ureterolithotomy, 8 PCNL and 4 ureteroscopic extraction. The renal function study determined individual and total renal function in terms of effective renal plasma flow (ERPF) at unilateral and bilateral kidneys. The mean total ERPF decreased 3-6 months after anatrophic nephrolithotomy (377.4 +/- 121.8 vs. 308.8 +/- 105.4 ml/min) or PCNL (447.4 +/- 152.3 vs. 386.8 +/- 140.8 ml/min) for staghorn stone. The mean ERPF of the kidney on the operative side decreased significantly to an extent of 29.4% up to 6 months after anatrophic nephrolithotomy. The mean ERPF on operative side increased significantly to an extent of 18.3% up to 6 months after ureterolithotomy. In conclusion, among the upper urinary stones, the unilateral (operative side) and total bilateral renal function decreased 1, 3, and 6 months, respectively, after anatrophic nephrolithotomy. On the contrary, the renal function increased significantly on the operative side up to 6 months after open ureterolithotomy. There was no significant change of mean ERPF at the kidney on operative or non-operative side in other kinds of upper urinary stones and surgical treatment.

Adult

Neobladder construction using completely detubularized sigmoid colon after radical cystoprostatectomy.

To improve the quality of life of the patient we used completely detubularized sigmoid colon for bladder reconstruction along with radical cystoprostatectomy in 6 men with invasive bladder cancer. Followup was 8 to 20 months. Postoperatively, all of the patients were continent during the day but only 4 (66.7%) were continent at night, although they had to awaken twice to remain dry. Neocystourethroscopy in 4 of the 6 patients revealed no tumor and no stricture at the urethrocolonic anastomosis. However, a stone in the neobladder was found in 1 patients. Urodynamic study of the neobladder showed a low pressure (mean 16.7 cm. water) at the filling phase of water cystometry and an adequate maximal urethral closure pressure (mean 52.0 cm. water) and functional profile length (mean 3.8 cm.). The uroflow rate in all patients was good (1 patient even had a maximal uroflow rate of 31 ml. per second). There was no reflux in any patient. One patient had intestinal obstruction 5 months postoperatively and died 5 months later of widespread metastasis. The remaining 5 patients are alive with a satisfactory quality of life. In conclusion, use of completely detubularized sigmoid colon may be an ideal operation for neobladder construction after radical cystoprostatectomy.

Adult

The incidence and prognostic significance of humoral hypercalcemia in renal cell carcinoma.

This retrospective study was conducted to evaluate the incidence and prognostic significance of humoral hypercalcemia in 218 renal cell carcinoma patients during the last 20 years. Of 218 patients 20 (9.2%) were hypercalcemic, with serum calcium levels ranging from 10.7 to 16.0 mg./dl. The respective incidence of humoral hypercalcemia was 3% in patients with stage I, 5.9% with stage II, 14.1% with stage III and 18.9% with stage IV disease without bone metastasis. The survival curves between the hypercalcemic and eucalcemic groups among stages I to III cancer patients showed no statistical significance (p greater than 0.05). The survival curve deteriorated significantly in stage IV cancer patients with humoral hypercalcemia (p less than 0.005), with a median survival of 45.0 +/- 39.7 days versus 286.4 +/- 27.6 days in eucalcemic patients. No specific correlation was found between pathological cell type and humoral hypercalcemia.

Carcinoma, Renal Cell

Prospective radionuclide renal function evaluation and its correlation with radiological findings in patients with Kock pouch urinary diversion.

In an attempt to understand better the status of renal function after Kock pouch urinary diversion we conducted a prospective evaluation of renal function in 25 patients using the radionuclide 131iodine-hippurate. Studies were done before, and at 1 month and every 6 months for 30 months postoperatively. The radionuclide results were then compared to excretory urography and contrast study of the reservoir. Our renal function study included the determination of individual and total effective renal plasma flow (ml. per minute), the time to maximal radioactivity over the kidney (peak time in minutes) and a renogram. The mean total (both kidneys) effective renal plasma flow rates before (25 patients) and at month 1 (19), month 6 (14), month 12 (12), month 18 (6), month 24 (6) and month 30 (7) after operation were 385.5 +/- 112.2, 310.5 +/- 109.9, 362.7 +/- 69.2, 442.0 +/- 97.5, 468.2 +/- 82.5, 405.7 +/- 70.6 and 414.0 +/- 65.1, respectively. A comparison of individual and total effective renal plasma flow before and after operation revealed that only the change of the flow at each or both sides of the kidney before and at 1 month after the operation reached statistically significant differences, respectively (p less than 0.05, paired t test). Postoperatively 5 of 6 patients with hydronephrosis had abnormal peak time and a third segment on the renogram was performed on the corresponding side of the kidney. No reflux was noted on contrast study of the reservoir of any patient followed for up to 30 months. In conclusion, the radionuclide renal function evaluation showed a significant decrease of renal function 1 month after Kock pouch diversion, then it resumed and remained stable (neither improved nor deteriorated) for 30 months. Also the abnormal peak time and third segment on the renogram usually implicated a dilated upper urinary tract.

Female

Cloning and characterization of a Pseudomonas mendocina KR1 gene cluster encoding toluene-4-monooxygenase.

Pseudomonas mendocina KR1 metabolizes toluene as a carbon source by a previously unknown pathway. The initial step of the pathway is hydroxylation of toluene to form p-cresol by a multicomponent toluene-4-monooxygenase (T4MO) system. The T4MO enzyme system has broad substrate specificity and provides a new opportunity for biodegradation of toxic compounds and bioconversions. Its known activities include conversion of a variety of phenyl compounds into the phenolic derivatives and the complete degradation of trichloroethylene. We have cloned and characterized a gene cluster from KR1 that determines the offO activity. To clone the T4MO genes, KR1 DNA libraries were constructed in Escherichia coli HB101 by using a broad-host-range vector and transferred to a KR1 mutant able to grow on p-cresol but not on toluene. An insert consisting of two SacI fragments of identical size (10.2 kb) was shown to complement the mutant for growth on toluene. One of the SacI fragments, when cloned into the E. coli vector pUC19, was found to direct the synthesis of indigo dye. The indigo-forming property was correlated with the presence of T4MO activity. The T4MO genes were mapped to a 3.6-kb region, and the direction of transcription was determined. DNA sequencing and N-terminal amino acid determination identified a five-gene cluster, tmoABCDE, within this region. Expression of this cluster carrying a single mutation in each gene demonstrated that each of the five genes is essential for T4MO activity. Other evidence presented indicated that none of the tmo genes was involved in the regulation of the tmo gene cluster, in the control of substrate transport for the T4MO system, or in major processing of the products of the tmo genes. It was tentatively concluded that the tmoABCDE genes encode structural polypeptides of the T4MO enzyme system. One of the tmo genes was tentatively identified as a ferredoxin gene.

Amino Acid Sequence

Serum iron as a tumor marker in renal cell carcinoma.

To evaluate the feasibility of using serum iron as a tumor marker for renal cell carcinoma, a retrospective review of serum iron, hemoglobin, hematocrit, mean corpuscular volume and pathology in patients with renal cell carcinoma was carried out. From January 1985 to December 1989, preoperative serum iron was obtained in 82 patients; 27 had stage I, 5 stage II, 23 stage III and 27 had stage IV disease. The serum iron levels (micrograms/dl) were 81.6 +/- 33.2 in stage I, 57.8 +/- 18.9 in stage II, 59.6 +/- 34.6 in stage III and 45.6 +/- 32.7 in stage IV disease, which were significantly lower as compared with the data (114.6 +/- 38.9) of a control group. Postoperative serum iron levels were available in 31 patients following nephrectomy and all showed an increase as compared with preoperative data except 2: 1 with recurrence and the other with progression of disease. It was concluded that the serum iron level may be used as a useful tumor marker in staging and follow-up of renal cell carcinoma.

Biomarkers, Tumor

Experience with percutaneous nephrostomy, extracorporeal shock wave lithotripsy and chemolysis in the treatment of obstructive uric acid stones.

Intravenous pyelography (IVP), retrograde ureteral catheterization and percutaneous nephrostomy (PCN) have been used to locate radiolucent stones during ESWL in an X-ray localization system lithotripter. We also used an alternative method combining PCN, ESWL and chemolysis to treat 8 obstructive uric acid stones. The average number of shock wave pulses was 1,725 (range 1,000-2,000), the generator voltage of the HM-3 Dornier lithotripter was 20-22 kV, and the local chemolysis lasted 4 days (range 2-7). All radiolucent uric acid stones were successfully disintegrated. Of the 8 patients treated, 5 were completely free of stones and the other 3 had insignificant residual stones after 3 months. Three patients who developed fever during local chemolysis with 0.1 M sodium bicarbonate solution were managed conservatively without severe sequelae. Only 1 patient retained a PCN tube after discharge. Because PCN can provide a path for local chemolysis and better localization, it is especially helpful in treating obstructive uric acid stones.

Bicarbonates

Penile brachial index in impotent patients with coronary artery disease.

From March to July 1989, a total of 40 patients, who had received coronary catheterization, answered questionnaires concerning sexual potency. In those 30 patients with a diseased coronary artery, only 2 (6.6%) had no erectile dysfunction subjectively. On the contrary, 4 of 10 (40%) patients with angiographically proven normal coronary artery complained of erectile dysfunction. Penile Doppler ultrasonography was performed in 30 patients. The mean penile brachial index (PBI) of 8 patients with a normal coronary artery was 0.82 +/- 0.1, as compared with the diseased group, 0.73 +/- 0.1 (p = 0.05). When these patients were further divided into two groups by a PBI of greater or less than 0.65, there was also no significant difference in the degree of obstruction of the three main coronary arteries between these two groups. There was no correlation between PBI and obstruction of the left anterior descending artery (r = 0.316, p = 0.689). Most of the patients (93.4%) with an abnormal coronary artery had erectile dysfunction. Nevertheless a poor correlation was noted between the PBI and the severity of coronary artery obstruction. Our study suggests that it is hard to use PBI alone as a predictor of future major thromboembolic heart attack.

Coronary Artery Disease

Clinical experience of Kock pouch continent urinary diversion.

Kock continent ileal reservoir for urinary diversion was performed in 53 patients with invasive bladder cancer (52) or neurogenic bladder (1). The postoperative follow-up period was from six to thirty-nine months. The clinical results showed no metabolic disturbance of blood electrolytes or acidity. Prolapse of efferent nipple valve developed in 4 patients (7.6%); and 2 underwent revisional surgery with a good result. Another 4 patients (7.6%) suffered from poor continence and relatively frequent catheterization to empty the pouch was necessary to prevent urine leakage through the stoma. Urodynamic study of the Kock pouch in these 4 patients showed a short functional nipple valve length and small pouch capacity. The other 45 patients (84.8%) had good continence. Urodynamic study of the pouch in 20 patients showed low pressure (mean of 13.3 cm H2O) in the pouch and high pressure (mean of 72.1 cm H2O) at the efferent nipple valve. Three patients had unilateral hydronephrosis in the follow-up intravenous urography. Corrective surgery for stenosis at the right ureteroileal anastomosis was done in 1 patient with normalization of the upper urinary tract afterward. The other 2 patients were managed by close observation for the mild hydronephrosis. Symptomatic bacteriuria developed in only 3 patients (5.7%) and responded well to antibiotic management. Reservoirography demonstrated no reflux into the upper urinary tract in all the follow-up patients. There was no significant change of the renal function at twenty-four months after operation detected by radionuclide (131I-Hippuran) renal functional study. All patients were satisfied with Kock urinary diversion.

Adolescent

Isolation and characterization of the gene encoding a novel, thermostable serine proteinase from the mould Tritirachium album Limber.

A number of proteinases are induced and secreted into the culture medium of Tritirachium album Limber when the nitrogen source is limited to exogenous proteins. We have constructed a cDNA library using the polyadenylated RNA isolated during the nutritional induction with bovine serum albumin. A full-length clone of a gene for a new proteinase (named proteinase R) was identified from this library. This clone contained sequences coding for the 108-amino-acid prepro-leader as well as for the 279-amino-acid mature proteinase. Proteinase R apparently belongs to the subtilisin group of serine proteases that contains disulphide bonds. Homology between proteinase R and proteinase K was found to be about 87% at the nucleotide as well as at the amino acid level. The Brookhaven Protein Data Base co-ordinate file of proteinase K was used as a template to study the proteinase R substitutions in three-dimensional space. The majority of the substitutions of proteinase R with respect to proteinase K were found to be on the exterior of the protein model.

Amino Acid Sequence