Coronary artery fistula diagnosed by transthoracic Doppler echocardiography.

A 47-year-old Malay woman complained of an episode of shortness of breath after a shower. There was no previous complaint of shortness of breath or chest pain. Physical examination revealed a wide pulse pressure. Blood pressure was 160/66 mmHg, and heart rate was 77/minute and regular. What was initially thought to be a loud pansystolic murmur was heard over the precordium. Electrocardiography showed left ventricular hypertrophy with a volume overload pattern. Transthoracic Doppler echocardiography revealed a right coronary artery-right ventricular fistula, arising from the right coronary artery and draining into the right ventricular cavity.

Differential modes of alaryngeal communication and long-term voice outcomes following pharyngolaryngectomy and laryngectomy.

Patterns of vocal rehabilitation for 37 pharyngolaryngectomy patients and 55 total laryngectomy patients over a 5-year period were compared. An electrolarynx (EL) was introduced as the initial communication mode immediately after surgery for 98% of patients, with 30% of pharyngolaryngectomy and 74% of laryngectomy patients subsequently developing tracheoesophageal speech (TES) as their primary mode of communication. Follow-up with 14 of 37 pharyngolaryngectomy patients and 36 of 55 laryngectomy patients was conducted 1-6 years following surgery and revealed that 90% of the pharyngolaryngectomy patients maintained the use of TES in the long term compared to 69% of the laryngectomy group. Long-term outcomes relating to communication disability and handicap did not differ significantly between the two surgical groups, however the laryngectomy patients had significantly higher levels of wellbeing. Across the whole group of patients, statistical comparison revealed that patients using TES had significantly lower levels of disability, handicap and distress than EL users. Considering that lower levels of disability, handicap and distress are associated with TES, and the data supports that suitably selected patients can maintain functional TES in the long term, increased application of this form of communication rehabilitation should be encouraged where viable for the pharyngolaryngectomy population.

Computerized analysis of fetal heart rate parameters by gestational age.

OBJECTIVE: The aim of this study is to define the reference ranges for fetal heart rate (FHR) parameters according to gestational age, by determining the relationship between the FHR and gestational age using a computerized FHR analysis system. METHODS: Using our own software developed by Hanyang University Hospital in Korea, non-stress tests were performed for 20 min. FHR parameters for 6455 subjects were analyzed for various gestational groups; <25 weeks, 25-28 weeks, 29-32 weeks, 33-36 weeks, 37-40 weeks, and >40 weeks. RESULTS: The FHR parameters were related to gestational age. The mean baseline FHR, signal loss, and fetal movements decreased significantly with gestation (P<0.0001). The variability and accelerations of FHR were highest for the 37-40 weeks gestational group (P<0.05). CONCLUSIONS: The results showed that overall, the differences in the FHR parameters between gestational groups were statistically significant, and the gestational age of the fetus should be considered when interpreting FHR patterns.

The influence of prostate volume on the prostate-specific antigen (PSA) level adjusted for the transition zone volume and free-to-total PSA ratio: a prospective study.

OBJECTIVES: To evaluate the influence of prostate volume on the prostate-specific antigen (PSA) level adjusted for the transition zone volume (PSAT) and free-to-total PSA ratio (f/tPSA) in detecting prostate cancer in men with intermediate PSA levels of 4.1-10.0 ng/mL. PATIENTS AND METHODS: From March 1997 to June 1999, the f/tPSA and PSAT were measured in 105 patients who underwent ultrasound-guided systemic biopsies and had a PSA level of 4.1-10.0 ng/mL, with an apparently normal prostate on a digital rectal examination. The PSAT and f/tPSA were evaluated in all patients and in subgroups of patients with small (< 40 mL) or large (> or = 40 mL) prostates, using receiver operating characteristic (ROC) curves. RESULTS: Total prostate volume was highly correlated with transition zone volume in all patients and in both subgroups (P < 0.001). In all 105 patients, PSAT had a sensitivity of 82% and its use would have avoided the largest number of unnecessary biopsies (87% specificity) at a threshold value of 0.35 ng. In men with small prostates f/tPSA and PSAT had a high sensitivity and specificity, at threshold values of 0.12 and 0.35 ng, respectively. In large prostates the PSAT was superior to f/tPSA in detecting prostate cancer. CONCLUSIONS: These results suggest that both f/tPSA and PSAT are useful in detecting prostate cancer in men with small prostates, while PSAT is superior to f/tPSA in detecting prostate cancer in men with large prostates.

Effects of acetaldehyde on responses of rabbit corpus cavernosal smooth muscle.

Ethanol has various effects on male sexual activity under the influence of direct and indirect, in acute and chronic alcohol ingestion. However, whether acetaldehyde, a principal metabolite of ethanol, may affect penile erection directly has still not been elucidated. This present study was, therefore, designed to clarify the pharmacologic effects of the acetaldehyde on corpus cavernosal smooth muscle. Corpus cavernosal strips were prepared from rabbit penises. Isometric tension changes of rabbit corpus cavernosal strips to various drugs and electrical field stimulation (EFS) in an organ chamber were recorded with a pressure transducer after active muscle tone had been induced by phenylephrine (10(-5) mol/L). At the concentrations employed, acetaldehyde had no effect on the pH of the bathing medium. Acetaldehyde in each concentration did not significantly affect resting tone of the smooth muscle during 30 min incubation. Acetaldehyde suppressed contractility induced by phenylephrine and KCI at 10(-4) mol/L, and relaxation induced by EFS and bethanechol at 10(-3) mol/L and 10(-4) mol/L respectively, but acetaldehyde enhanced relaxation induced by ATP at high acetaldehyde level. Sodium nitroprusside-induced relaxation was not affected at any employed acetaldehyde concentration. This suggests that increasing the acetaldehyde level may contribute to male erectile dysfunction mainly by the inhibition of nitric oxide formation.

Adenovirus-mediated suicide-gene therapy using the herpes simplex virus thymidine kinase gene in cell and animal models of human prostate cancer: changes in tumour cell proliferative activity.

OBJECTIVES: To determine the feasibility and efficacy of suicide-gene therapy using adenovirus (Ad)-mediated herpes simplex virus thymidine kinase (HSV-TK) and the prodrug acyclovir, and to evaluate changes in the biological phenotype for tumour cell proliferative activity after suicide-gene therapy in animal models of human prostate cancer. MATERIALS AND METHODS: Using a replication-defective adenoviral vector (cytomegalovirus, CMV) containing the beta-galactosidase gene (Ad-CMV-beta-gal) as a control and Ad-CMV-TK as the therapeutic vector under the transcriptional control of the CMV promoter, transduction efficiency was assessed in vitro by infecting LNCaP and PC-3 androgen-dependent and independent human prostate cancer cells with Ad-CMV-beta-gal, and using X-gal staining. The TK activity in prostate cancer cells infected with Ad-CMV-TK was determined by measuring TK-mediated [3H]-gancyclovir phosphorylation. The sensitivity of LNCaP and PC-3 cells to Ad-CMV-TK in vitro was determined after infection with the therapeutic vector with or without acyclovir. The inhibition of PC-3 tumour growth in vivo induced by the Ad-CMV-TK/acyclovir suicide-gene system was assessed in separate and controlled experiments using human prostate cancer mouse models. Ki-67 proliferative antigen and proliferating cell nuclear antigen (PCNA), both useful proliferative indices, were evaluated using immunohistochemical staining (MIB-1 monoclonal antibody and monoclonal anti-PCNA antibody) in formalin-fixed, paraffin-embedded tissues from gene therapy-treated and control animals. RESULTS: The mean TK activity was significantly higher in LNCaP and PC-3 cells infected with Ad-CMV-TK than in cells infected with Ad-CMV-beta-gal, used as a control (P < 0.05). The growth of human prostate cancer cells with Ad-CMV-TK was significantly inhibited by adding acyclovir in vitro (P < 0.05). In the in vivo experiments using the PC-3 human prostate cancer mouse model, tumour volume and growth was lower in mice treated with Ad-CMV-TK/acyclovir than in those treated with Ad-CMV-TK only, acyclovir only or untreated (controls) (P < 0.05). Histochemical staining of tumour tissues showed that Ad-CMV-TK/acyclovir destroyed PC-3 tumours through tumour cell death and apoptosis, with local lymphatic infiltration. The mean PCNA labelling index in prostate cancer cells of mice treated with Ad-CMV-TK/acyclovir was significantly lower than that in untreated controls (P < 0.05, Mann-Whitney U-test). The Ki-67 labelling index in prostate cancer cells of mice treated with Ad-CMV-TK/acyclovir was also lower than that in untreated controls (P < 0.05, Student's t-test). Adenovirus-mediated suicide-gene therapy using the HSV-TK gene decreased the proliferative activity of PC-3 human prostatic cancer cells in vivo. CONCLUSIONS: Adenovirus-mediated suicide-gene therapy using an HSV-TK/acyclovir system provided effective therapy in an experimental human prostate cancer mouse model, by significantly inhibiting tumour growth and decreasing the proliferative activity of human prostate cancer cells. Such therapy could be developed as a novel method for treating patients with androgen-independent prostate cancer.

Allium sativum potentiates suicide gene therapy for murine transitional cell carcinoma.

This study evaluated the synergistic effect of Allium sativum (AS) with suicide gene therapy for transitional cell carcinoma (TCC) of the bladder. Subcutaneous TCCs were established in syngeneic C3H/He mice with 1 x 10(5) MBT-2 cells. AS liquid extract was injected at the site of tumor transplantation on Day 1 for three weeks (Experiment I) and into the established tumors weekly for five weeks (Experiment II) in combination with or without gene therapy using a replication-defective adenoviral vector containing a herpes simplex virus thymidine kinase (HSV-TK) gene under the transcriptional control of Rous sarcoma virus (RSV) promoter (Ad-RSV-TK, 5 x 10(8) plaque-forming units) plus ganciclovir (20 mg/kg/day i.p.). AS demonstrated a statistically significant reduction in incidence of TCC (cumulative dose 25 mg of AS). Combination AS-suicide gene therapy significantly inhibited the tumor growth compared with the controls, which was evidenced by apoptosis on histomorphological and immunohistochemical studies. These results suggest that AS had a definite antitumor effect in inhibiting tumorigenesis and growth of TCC in a murine model. AS treatment combined with suicide gene therapy had significant additive antitumor effects on TCC and may provide a novel and effective treatment modality for TCC of the bladder.

Prostate-specific antigen adjusted for the transition zone volume versus free-to-total prostate-specific antigen ratio in predicting prostate cancer.

BACKGROUND: We performed this study to assess the efficacy of prostate-specific antigen adjusted for the transition zone volume (PSATZ) and free-to-total prostate-specific antigen (PSA) ratio (F/T ratio) in predicting prostate cancer in men with intermediate PSA levels of 4.1-10.0 ng/mL. METHODS: Between March 1997 and September 1998, PSATZ was obtained from 67 patients who underwent ultrasonography guided systemic sextant biopsies and had a PSA of 4.1-10.0 ng/mL. PSATZ was compared with F/T ratio via receiver operating characteristic (ROC) curves. RESULTS: Of 67 patients, 22 (32.8%) had prostate cancer and 45 (67.2%) had benign prostatic hyperplasia (BPH) on pathologic examination. Mean PSA, PSA density, F/T ratio and PSATZ were 7.96+/-2.01ng/mL, 0.28+/-0.14 ng/mL/cc, 0.10+/-0.06 and 0.70+/-0.28 ng/mL/cc in patients with prostate cancer and 6.39+/-1.68 ng/mL, 0.16+/-0.06 ng/mL/cc, 0.15+/-0.05 and 0.29+/-0.10 ng/mL/cc in patients with BPH, respectively. The ROC curve analysis demonstrated that PSATZ predicted the biopsy outcome significantly better than F/T ratio in all 67 patients (P<0.01) and in a subset of 53 men with normal digital rectal examination (P<0.01). With a cut-off value of 0.35 ng/mL/cc, PSATZ had a sensitivity of 86% and a specificity of 89% for predicting prostate cancer. CONCLUSIONS: These results suggest that PSATZ and F/T ratio may be useful in diagnosing prostate cancer with intermediate levels of PSA. Prostate-specific antigen adjusted for the transition zone volume is more accurate than F/T ratio in distinguishing benign prostatic disease from prostate cancer. But large prospective studies are required to assess the precise role of PSATZ and F/T ratio in early prostate cancer detection.

The role of nitric oxide in vivo feline erection under hypoxia.

Previous in vitro studies have demonstrated that the cavernous relaxation under hypoxia does not involve the endothelium dependent mechanism. However, the mechanism of nitric oxide pathway under hypoxia are not fully evaluated or understood yet in vivo. The changes of intracavernous pressure to various vasoactive substances were monitored in 45 mature male cats in vivo under normoxia and hypoxia (pH: 7.03, PO2: 25.52 mmHg, PCO2: 84.66 mmHg). L-arginine and SNAP (s-nitroso-n-acetyl-penicillamine) produced cavernous relaxation under normoxia, but not under hypoxia (n = 19, P < 0.01). The L-arginine-induced relaxations were inhibited by L-NAME (N omega-nitro-1-arginine-methyl-ester) or methylene blue under normoxia (n = 19, P < 0.01). The cavernous relaxation was 58% suppressed under hypoxia compared to normoxia with 10(-3) M/0.2 ml of acetylcholine (n = 22, P < 0.01). Moreover, L-NAME attenuated the acetylcholine-induced relaxation under normoxia, but not under hypoxia (n = 22, P < 0.05). Epinephrine suppressed the acetylcholine-induced relaxation in both conditions (n = 10, P < 0.01), while indomethacin significantly potentiated the acetylcholine-induced relaxation under normoxia compared to hypoxia (n = 6, P < 0.05). However, none of these substances responded in severe hypoxia (PO2 < 15 mmHg, n = 3). These results suggest that erectile and contractile responses are attenuated under hypoxia. The endothelium derived relaxation via nitric oxide does not play a role in cavernous relaxation under definitive hypoxia with acidosis like in ischemic priapism (PO2 < 30 mmHg, pH < 7.25).

Inhibitory effects of interleukin-4 on human renal cell carcinoma cells in vitro: in combination with interferon-alpha, tumor necrosis factor-alpha or interleukin-2.

BACKGROUND: Immune cytokines have been shown to play important roles in regulating the growth of neoplastic cells, as well as the function of immune cells. The present study assessed the effects of interleukin (IL)-4 alone, and in combination with recombinant interferon (IFN)-alpha 2b, or with IL-2, or with tumor necrosis factor (TNF)-alpha on the in vitro proliferation of human renal cell carcinoma (RCC) cell-lines. METHODS: Growth-inhibitory effects of IL-4 alone, and in combination with other cytokines, on three human RCC cell-lines, Caki-1, CURC-II, and A-498, were measured by the [3H]thymidine incorporation assay. RESULTS: IL-4 inhibited proliferation of all three human RCC cell-lines (P < 0.001). The maximum growth inhibition of RCC cell-lines by IL-4 alone was observed at the concentration of 1 to 3 ng/mL, depending on the cell-line. Antihuman IL-4 antisera was able to reverse the growth-inhibitory effects of IL-4 on Caki-1 in a dose-dependent manner, proving that the growth inhibition was mediated by IL-4 itself. When other cytokines were added in combination with IL-4, only IFN-alpha 2b resulted in significant additional growth inhibition (P < 0.005). However, when the proliferation was compared to that of RCC cells that were not treated with any cytokine, all combinations produced marked growth inhibition. CONCLUSION: Our data suggest that IL-4 alone, or in combination with IFN-alpha 2b, can be used to develop new strategies for treatment of human RCC.

Malignant inverted papilloma of the urinary bladder: the histopathological aspect of malignant potential of inverted papilloma.

To investigate the histopathological characteristics of inverted papillomas of the urinary bladder, including the possibility of malignant transformation, we studied the indicators of cellular proliferation activity in 7 inverted papillomas of the bladder including two cases of malignant inverted papilloma of the bladder. PCNA expression rates in two cases of malignant inverted papilloma were higher than in benign inverted papillomas. Mean numbers of AgNORs per nucleus in malignant inverted papillomas were much more than in benign inverted papillomas. The c-erbB-2 oncoprotein was expressed only in malignant inverted papillomas. These results suggest that PCNA expression rate, mean number of AgNORs per nucleus and c-erB-2 oncoprotein expression may be merited as good indicators to detect the inverted papilloma with more proliferative and aggressive lesions, and with the potential of malignant transformation.

Spinal bone mineral density of normal and osteoporotic women in Korea.

In order to define osteoporosis on the basis of bone mineral measurements, one must define an acceptable normal range or fracture threshold. It is clear that the normal range cannot be compared between different ethnic groups. We have measured spinal bone mineral density (BMD) by dual photon absorptiometry in 277 women without spinal fracture, aged 30-91 years, and in 53 women with asymptomatic spinal fracture to provide such a database for normal Korean women. Peak bone mass at the 3rd decade was 1.24 g/cm2. BMD from age 40-69 was strongly correlated with age (r = -0.7) and the annual decrease averaged 0.018gm/cm2. The rate of annual loss slowed by 50% in women after 70% years of age. Fracture threshold was evaluated at the 90th percentile for spinal BMD in patients with vertebral fractures. The fracture threshold of the vertebra was 0.94 g/cm2. Approximately 50% of normal women over 50 years of age had values below this threshold. These findings suggest that the way of developing low bone mass in Korean women is to peak high and lose fast.

Incidence estimation of genitourinary cancer in Korea.

A nation-wide study was performed to estimate the incidence of bladder, kidney, renal pelvis and ureter, prostate, testicular and other genitourinary cancer among Koreans in Korea using medical records of the inpatients of the beneficiaries of the Korea Medical Insurance Corporation (KMIC) from Jan. 1, 1989 to Dec. 31, 1989. The crude incidence rate of bladder cancer (ICD-9 188) is estimated to be 4.43 and 0.98 per 100,000 in males and females, respectively. Around 1,093 new cases of bladder cancer (895 male and 198 female) are estimated to occur in a year. The adjusted rate for the world population is 7.76 in males and 1.19 in females which is similar to that of Japanese in Osaka and Chinese in Shanghai, but lower than in American whites and blacks. The crude incidence of kidney, renal pelvis and ureteral cancer (ICD-9 189) is estimated to be 1.61 and 0.87 in males and females, respectively. Around 507 new cases of kidney, renal pelvis and ureteral cancer (332 male and 175 female) are estimated to occur in a year. The adjusted rate for the world population is 2.69 in males and 1.04 in females. In the prostate (ICD-9 185), the crude incidence rate of cancer is estimated to be 1.36. Around 274 new cases of prostate cancer are occurring in a year. The adjusted rate for the world population is 2.98 which is similar to the Chinese rate. The incidence of genitourinary cancer continuously increases with age.

A survey of externally recognizable genitourinary anomalies in Korean newborns. Korean Urological Association.

To estimate the incidence of externally recognizable genitourinary anomalies and associated anomalies in the newborns in Korea, retrospective and prospective studies have been performed. Thirty eight of 48 urology training hospitals participated in this nationwide survey. In this study we have included minor defects or variations in the anomaly to evaluate the incidence of the recognizable genitourinary conditions in the newborns. The incidence of genitourinary anomaly in 1,000 newborn delivery in a year was 11.0 in the prospective study and this figure is about three times higher than the retrospective study and is considered to be close to the true incidence. The incidence of genitourinary anomaly in 1,000 male newborn was 20.4. Hydrocele, cryptorchidism and hypospadias were most commonly observed. The incidence of hydrocele in 1,000 male newborn was 9.89 and the incidence of cryptorchidism was 7.26 and the incidence of hypospadias was 2.13. The incidence of associated anomaly in 100 genitourinary anomaly was 7.9. Congenital heart diseases and anorectal anomalies were commonly associated anomalies. In the newborns with genitourinary anomalies, premature infants account larger portion than is usually reported in total delivery.

A study of the effectiveness of inosine in renal transplantation.

Kidneys preserved with cold Collins' solution only function satisfactorily if there is no significant preceding period of warm ischaemia. This paper reports an attempt to provide protection to renal function during such a warm ischaemic episode using the nucleotide inosine. In these experiments inosine given intravenously to dogs followed by 15 min of warm renal ischaemia and by either 12 or 24 h of cold preservation with Collins' solution did not protect renal function against the warm ischaemic insult.