Intraarterial chemotherapy as the first-line therapy in penile cancer.

BACKGROUND: Limited literature on the role of intraarterial chemotherapy as first-line therapy for penile squamous cell carcinoma is available. METHODS: From 2005 to 2013, a total of 12 patients with various stages of penile squamous cell carcinoma received intraarterial chemotherapy. The chemotherapeutic agents used were methotrexate, mitomycin C, bleomycin, cisplatin, and 5-fluorouracil. Surgery was followed by the tumour responses. RESULTS: An objective tumour response was noted in 10 of 12 patients (83%, 4 complete responders and 6 partial responders). In node-negative patients (n=7), the response rate was 100% (4 complete responders and 3 partial responders). Even in advanced penile squamous cell carcinoma with nodal invasion, a response rate of 60% could be achieved. Grade 2 anorexia was the most frequent chemotherapy-related toxicity and no toxic death was noted. Recurrence-free survival was significantly better in patients without lymph node invasion (log-rank test, P=0.041). CONCLUSIONS: Neoadjuvant intraarterial chemotherapy displayed excellent responses for penile squamous cell carcinoma. This therapy could effectively shrink the tumour burden or even achieve complete response before surgery. It could be used as first-line strategy for penile cancer treatment because of low toxicity.

Toxicological analysis points to a lower tolerable daily intake of melamine in food.

Intensified food safety concern over melamine has prompted national authorities to assess its tolerable daily intake (TDI) for protection of general population including young children. TDI is calculated by dividing a no-observed-adverse-effect level (NOAEL) by a safety factor (SF). Based on appropriate choices of values, the US Food and Drug Administration determined two TDI values in the unit of mg per kg body weight per day as first 0.63 and then 0.063, while the World Health Organization, 0.5 and then 0.2, as a result of increasing the SF values in calculation. We used a similar procedure, with judicious selection of pertinent values, to obtain a TDI of 0.0081. Arguments in support of this lower TDI value were provided to alert the international community.

Continuous compression behaviors of selective laser melting Ti-6Al-4V alloy with cuboctahedron cellular structures.

Cellular structures often show fluctuating stresses in compression stress-strain curves. Such fluctuating stresses correspond to strut fractures. In this study, the cellular Ti-6Al-4V alloy with cuboctahedron structure was prepared by selective laser melting. The cuboctahedron cellular structures showed reduced fluctuations in their compressive stress-strain curves after the initial yielding peak. Their moduli were modulated via the porosity of the structure by changing the strut diameter. A compressive modulus of between 1.3 and 4.868 GPa can be achieved by varying the porosity in the cellular structures between 33% and 84%. Both heat treatment and hot isostatic press (HIP) treatment reduced the fracture strength of the struts during compression due to the conversion of the α' martensite phase into the more ductile α +â€¯ß phase. The cellular structure with HIP treatment produced a continuous stress-strain curve during compression, indicating uniform strain distribution behavior. The continuous compressive stress-strain curve can lead to reduced debris formation during compression processes. The deformation showed either bending or stretching mechanisms depending on whether the supports were included along the building direction. The design concepts of cellular structures demonstrated in this study will be valuable in future biomedical applications.

Human Polyomavirus Is Associated With Earlier Onset of Upper Urinary Tract Urothelial Carcinoma in Patients After Kidney Transplantation.

OBJECTIVES: Polyomavirus has been reported to be oncogenic due to viral integration into the human genome. A relatively high prevalence of upper urinary tract urothelial carcinoma (UTUC) was noted after kidney transplantation (KT) in Taiwan. However, little was known about the impact of polyomavirus on the urothelial cancer behavior. Therefore, the aim of this study is to analyze the characteristics of polyomavirus-related UTUC after KT. METHODS: From 2005 to 2014, 27 patients were found to have UTUCs after KT. All the patients underwent standard nephroureterectomy. Detailed perioperative parameters were obtained from chart records. A qualified pathologist who is blinded to the clinical outcome examined large T antigen expression and pathological features. All the patients were divided into two groups according to positive or negative expression of large T antigen. RESULTS: In the patient demography, a significantly younger median age was found in patients with large T antigen-positive UTUCs compared with the negative control group (48.1 ± 8.3 years versus 54.6 ± 4.1 years, respectively, P = .013). As for the pathological features and oncologic outcome, there were no obvious differences between these two groups. Non-organ-confined status and positive lymphovascular invasion are prognostic factors associated with systemic disease recurrence (P = .017 and .001, respectively). CONCLUSIONS: Although UTUC commonly develops in the elderly, earlier onset of post-KT UTUCs was observed especially in patients with positive large T antigen expression in our cohort. This preliminary result provides valuable experience suggesting more frequent upper urinary tract screening for polyomavirus infected patients after KT in Taiwan.

Molecular cloning and nuclear localization of a histone deacetylase homologue in Plasmodium falciparum.

Reversible acetylation of core histones plays an important role in transcriptional regulation, cell cycle progression and developmental events. The acetylation state of histones is controlled by a dynamic equilibrium between activities of histone acetylase and deacetylase enzymes. Histone deacetylase (HDAC) was recently suggested to be the target of a fungus-derived antiprotozoal agent exhibiting structural similarity to known HDAC inhibitors. We have initiated a study of HDAC of human malaria parasite, Plasmodium falciparum, to evaluate its potential as the target for novel antimalarials and its role in parasite development. We have isolated HDAC1 gene from the P. falciparum genomic and cDNA libraries. The nucleotide sequence contains no intervening sequence and its open reading frame (ORF) codes for a protein of 449 amino acid residues. We have named the protein, PfHDAC1, as the sequence shows significant homology to yeast, human and other eukaryotic HDACs. Northern blot analysis of the total RNA from different asexual and sexual stages of the parasite reveals the presence of single mRNA transcript, which is predominantly expressed in mature asexual blood stages and in gametocytes. Antiserum raised against a carboxyl terminal peptide immunoprecipitated an in vitro translated P. falciparum HDAC gene product and recognized an approximately 50 kDa protein in the Triton X-100 insoluble fraction of parasites. Immunoelectron microscopy analysis showed majority of the protein localized in the nucleus of P. falciparum. To our knowledge, this is the first HDAC gene isolated from the malaria parasite.

Tracking the assembly pathway of human immunodeficiency virus type 1 Gag deletion mutants by immunogold labeling.

The Pr55gag gene product of human immunodeficiency virus type 1 (HIV-1) is sufficient to direct the formation of retrovirus-like particles (RVLPs). Recent biochemical evidence has indicated the presence of Gag intermediates in the cytoplasm; however, the Gag assembly process into RVLPs remains incompletely defined. The authors present here the subcellular localization of Gag mutant proteins in BSC40 and Jurkat cells by immunoelectron microscopy (IEM). The full Gag/Pol and Gag precursors, a C-terminal deletion mutant lacking a portion of nucleocapsid (NC), and all p6Gag gave rise to similar levels of RVLPs at the cell surface. A C-terminal deletion of all NC and p6Gag abrogated particle formation, whereas p24 was found in patches at the cell surface. Deletion of matrix (MA) sequences from Gag resulted in intracellular particles, and myristylation was not required for particle formation in the context of the MA deletion. Matrix expression was enhanced with Gag/Pol or Env coexpression as determined by semiquantitative IEM. p24 protein was targeted at vacuolar and mitochondrial membranes, but not at Golgi cisternae. In addition, aggregations of Gag intermediates and RVLPs in the cytoplasm, rough endoplasmic reticulum, cisternae, and mitochondria were noted. These results provide defined in situ evidence that HIV-1 particle assembly occurs in the cytosol in addition to budding at most intracellular membranes.

Pilot study of transurethral needle ablation (TUNA) in treatment of nonbacterial prostatitis.

Transurethral needle ablation (TUNA) was performed on seven patients with chronic nonbacterial prostatitis who failed to respond to conventional treatments administered for more than half a year. The TUNA procedure heated the prostate to a temperature ranging from 90 degrees to 100 degrees C while the urethral temperature was maintained below 43 degrees C by a protective sheath and irrigation. After treatment, four patients showed complete resolution of symptoms and three a partial improvement. All patients had a decrease in the leukocyte count in expressed prostatic secretions (EPS) 1 month after treatment. Recurrence of abnormal inflammatory cells in the EPS was noted in two patients at 3 months after treatment. The subjective improvement has been maintained during the subsequent follow-up. From these results, TUNA is considered to be an effective, safe, and easy treatment for most patients with nonbacterial prostatitis.

Adenosine stimulates human sperm motility via A2 receptors.

The effects of adenosine and its analogues on human sperm motility were studied using a transmembrane migration method. Specific binding sites for adenosine in human sperm were also investigated. Adenosine and 5'-N-ethylcarboxamidoadenosine (NECA) stimulated human sperm motility with similar efficacies and the maximal amplitudes of motility increases were both about 70%. 3,7-Dimethyl-1-propargylxanthine (DMPX), a potent A2 antagonist, competitively antagonized NECA-induced motility stimulation. Successively higher concentrations of DMPX shifted the dose-response curve of NECA to the right in a nearly parallel fashion. Dipyridamole, an inhibitor of adenosine uptake, does not reduce the ability of adenosine to stimulate human sperm motility. In radioligand-binding studies, adenosine A1 selective analogues, cyclopentyl-1,3-dipropylxanthine and 1-methyl-2-phenylethyl adenosine, have little competitive effect on [3H]NECA binding in human sperm membrane. These results provide evidence that adenosine enhances human sperm motility via adenosine A2 receptors on the surface of sperm membranes.

Orthotopic bladder substitution in women using the ileal neobladder.

Before 1990, orthotopic bladder substitution was limited to men and urethrectomy was routinely performed in women--making orthotopic reconstruction impossible. Following studies on pelvic exenteration for transitional cell bladder cancer patients, and after anatomic studies of the female urethra, the first report on orthotopic bladder substitution was published in 1994. Here, we present our ileal neobladder technique, which was applied for the treatment of bladder cancer in three women, and sigmoid colon cancer with vesical metastasis in one woman. This surgical procedure preserves the urethral sphincter, the endopelvic fascia, and the pubourethral ligaments. The innervation of the sphincter is also maintained. A 45-cm segment is isolated from the distal ileum and arranged in a W-shaped configuration. An anastomosis between the ileal bladder and the urethra is made and an antireflux ureteroileal implantation is created. Postoperatively, all patients reported daytime continence. The average urinary flow rate was 13.5 +/- 2.1 mL/sec 3 months after surgery. The reservoir had low pressure and high capacity. There was no reflux or deterioration of renal function. In properly selected female patients undergoing radical cystectomy, an ileal neobladder is now an option.

Giant hydronephrosis: report of 4 cases with review of the literature.

Giant hydronephrosis is uncommon. In 1939, Stirling defined it as the presence of more than 1,000 ml of fluid in the collecting system [1]. We herein report 4 cases of giant hydronephrosis containing 1,900 ml, 3,400 ml, 2,100 ml and 3,200 ml, respectively. Only 6 cases with a malignant tumor have been reported in the literature. Our second case with multiple foci of transitional cell carcinoma with squamous metaplasia is presented. This is the first report of this kind of pathological morphology with giant hydronephrosis. An erroneous diagnosis is often made in cases of giant hydronephrosis. For example, 3 of our 4 patients were first diagnosed as ovarian cyst, retroperitoneal hamartoma and hepatic cyst, respectively. We have found 523 cases reported in the literature. It is seen more often in males than in females (2.4:1) and more often on the left side than on the right side (1.8:1). The amount of fluid in the hydronephrotic sac is often between 1 and 2 liters. It is usually secondary to ureteropelvic junction obstruction, stones or congenital abnormality. Nephrectomy is often performed due to severe impairment of renal function. Acute renal failure and cardiopulmonary distress developed in our second case after the operation. The reason may be the sudden decompression of the huge hydronephrotic sac, which resulted in a change in the hemodynamic balance. Therefore, a two-stage procedure with slow decompression by percutaneous nephrostomy before the nephrectomy is preferred in the compromised patient.

Intravesical mitoxantrone in superficial bladder cancer.

Twenty-five patients with Ta-T1 transitional cell carcinoma of the bladder were treated by transurethral resection (TUR) followed by intravesical chemoprophylaxis with mitoxantrone (10 mg diluted in 50 ml normal saline) administered weekly for 6 weeks. After a mean follow-up of 12 months, 76% of patients in the whole group, 69% in the newly diagnosed patients and 89% in the group of previously relapsed patients remained relapse free. These rates compare favorably with the other prophylactic agents available. Therapy was well tolerated in most patients, with only two patients reporting grade 3 local toxicity. We conclude that mitoxantrone is an effective and safe agent for intravesical chemotherapy.

Retroperitoneal laparoscopic nephrectomy in the treatment of incontinence from ectopic ureter with renal hypoplasia in the child--a case report.

Unilateral single vaginal ectopic ureteral opening with ipsilateral hypoplastic kidney is a rare disease. It is classically presented with continuous urinary incontinence, but a normal voiding pattern after successful toilet training. The kidneys associated with this condition are usually nonfunctional and nephrectomy is the treatment of choice to cure the incontinence. We present a 7-year old girl with such a problem successfully treated by retroperitoneal laparoscopy. The patient resumed her normal unrestricted activity level on postoperative day 3. She was free of symptoms related to the operation during a 6-year follow-up period. It is suggested from this case that despite the reduced working space in children, retroperitoneal laparoscopic nephrectomy in the treatment of small kidney with complications is a feasible procedure.

Transurethral needle ablation of the prostate (TUNA) in the treatment of chronic urinary retention.

The transurethral needle ablation (TUNA) of the prostate was performed in 8 patients in chronic urinary retention, all of whom were a poor surgical risk. A special catheter device was used to deliver low-level radiofrequency energy to heat tissue within the prostate to 100 degrees C. After treatment, uroflowmetry, symptom score and quality of life score were evaluated. Tolerance of the procedure with topical anesthesia was satisfactory. Of the 8 patients, 6 (75%) resumed voiding within a mean time of 9.2 days (range 1-21). The mean maximal flow rate was 9.8 +/- 3.2 ml/s (range 5.9-14). Failure to void was associated with a decompensated detrusor function. We conclude that TUNA is effective for patients with urinary retention due to benign prostatic hyperplasia. It seems particularly suitable for treating elderly patients with a high surgical risk.

Nerve-sparing radical cystoprostatectomy: 3-year experience.

From June 1993 through January 1996, ten men underwent nerve-sparing radical cystoprostatectomy for carcinoma of the bladder. We describe a modification of surgical technique in which the puboprostatic ligaments are left intact and dissection of neurovascular bundle is performed immediately after the ligation of dorsal vein complex. Rigiscan was performed in 7 patients and 4 patients had good rigidity. Color duplex sonography revealed 8 of 10 patients had peak systolic velocity over 30 cm/sec after the injection of prostaglandin E1. Maintenance of sexual function was stated by seven (70%) patients. These is no positive surgical margin. We conclude that the nerve-sparing modifications are possible to preserve potency in most men undergoing radical cystoprostatectomy and do not compromise cancer control.

Effects of adenyl purines in human uterine arteries and uterine myometrium.

This in vitro study was undertaken to investigate the effects of adenyl purines in human uterine myometrium and uterine arteries. Segments of uterine myometrium and uterine arteries obtained at hysterectomy were isolated and mounted in tissue chambers. The muscle activity was recorded by polygraph. Adenyl purines agonists, such as adenosine, N-[(R)-1-methyl-2 phenylethyl]-adenosine (R-PIA) and 5-N-ethylcarboxamide adenosine (NECA) produced concentration-dependent contraction in human uterine myometrium. The potency order was NECA = R-PIA > adenosine. Adenosine A1 receptor antagonist: 1, 3-dipropyl-8-cyclopentylxanthine (DPCPX) blocked the effect of adenosine in human uterine myometrium. Otherwise, adenyl purines induced dose-dependent relaxation in human uterine artery precontracted by phenylephrine (PE, 10(-5)M). The potency gradient was NECA > R-PIA > adenosine; the results indicate adenyl purine induces uterine myometrium contraction via A1 receptor. However, adenosine causes uterine artery relaxation by A2 receptor.

The experiences of rectosigmoid pouch as a continent urinary diversion after radical cystectomy.

Thirty-five patients receiving cystectomy underwent rectosigmoid pouch. The technique of ureteral submucous implantation was described. The follow-up results were analyzed. The relationship of postoperative voiding frequency and preoperative anal closure pressure was assessed. The day and night time continence rate is 97% (34/35). There were no hydronephrosis, no ureterocolonic stricture or reflux. The complications are not unique to rectosigmoid pouch and not high when compared with other forms of urinary diversion. When the preoperative anal closure pressure reaches nearly 100 cmH2O a postoperative outcome with good quality of life will be predicted. With the advantages of high continence rate and simplicity of performance the rectosigmoid pouch will become one of the alternative forms of continent urinary diversion. For obtaining the favorable results a patient with normal renal function, good hepatic function and anal closure pressure more than 50 cmH2O is required.

Survival benefits of metabolic syndrome among older men aged 75 years and over in Taiwan.

BACKGROUND: Metabolic syndrome (MetS) was common in the elderly, but its prognostic significance in older old population remained unclear. The main purpose of this study was to evaluate the survival impact of MetS among older men aged 75 and over in Taiwan. METHODS: From 2008, residents aged 75 years and older of Banciao Veterans Home were invited for study and were followed for 3 years. All participants received history taking, physical examinations, and laboratory tests. Mortality was determined by Veteran Affairs Death Registry, which was linked to the National Death Registry. RESULTS: Overall, 680 men (mean age: 82.5±4.7 years) were enrolled for study and the prevalence of MetS was 31.6%. During the follow-up period, 140 (20.6%) participants died, and the causes of death included infectious diseases (62, 9.1%), cardiovascular disease (37, 5.4%), cancer (20, 2.9%), and others (21, 3.1%). MetS subjects had a significantly higher prevalence of hypertension, diabetes mellitus, and having higher body mass index, waist circumferences, systolic blood pressure, fasting blood glucose, serum triglyceride and lower HDL-C level than non-MetS subjects. However, MetS subjects were less likely to die during study period (16.3% vs. 22.6%, P=0.059). Multivariate logistic regression showed that older age (OR:1.04, 95% C.I.: 1.00-1.08, P=0.04), diabetes mellitus (OR: 2.10, 95% CI: 1.34-3.30, P=0.001) were independent risk factors for mortality; and serum total cholesterol and triglyceride were protective factors (OR: 0.99, 95% CI: 0.99-1.00, P=0.037 for cholesterol; OR: 0.99, 95% CI: 0.99-1.00, P=0.013 for triglyceride). Adjusted for age, diabetes mellitus, serum levels of total cholesterol, and triglyceride, MetS played a potential trend of survival benefits among study subjects (HR: 0.71, 95% CI: 0.45-1.12, P=0.144). CONCLUSIONS: The prevalence of MetS among men aged 75 years and over was 31.6%, and the 3-year mortality rate was 20.6%. Older age, diabetes mellitus, lower serum cholesterol and lower serum triglyceride were independent risk factors for mortality. Further investigation is needed to clarify the prognostic impact of MetS in older adults.

M(1)-like muscarinic acetylcholine receptors regulate fast-spiking interneuron excitability in rat dentate gyrus.

Cholinergic transmission through muscarinic acetylcholine receptors (mAChRs) plays a key role in cortical oscillations. Although fast-spiking (FS), parvalbumin-expressing basket cells (BCs) are proposed to be the cellular substrates of gamma oscillations, previous studies reported that FS nonpyramidal cells in neocortical areas are unresponsive to cholinergic modulation. Dentate gyrus (DG) is an independent gamma oscillator in the hippocampal formation. However, in contrast to other cortical regions, the direct impact of mAChR activation on FS BC excitability in this area has not been investigated. Here, we show that bath-applied muscarine or carbachol, two mAChR agonists, depolarize DG BCs in the acute brain slices, leading to action potential firing in the theta-gamma bands in the presence of blockers of ionotropic glutamate and gamma-aminobutyric acid type A receptors at physiological temperatures. The depolarizing action persists in the presence of tetrodotoxin, a voltage-gated Na(+) channel blocker. In voltage-clamp recordings, muscarine markedly reduces background K(+) currents. These effects are mimicked by oxotremorine methiodide, an mAChR-specific agonist, and largely reversed by atropine, a non-selective mAChR antagonist, or pirenzepine, an M(1) receptor antagonist, but not by gallamine, an M(2/4) receptor antagonist. Interestingly, in contrast to M(1)-receptor-mediated depolarization, M(2) receptor activation by the specific agonist arecaidine but-2-ynyl ester tosylate down-regulates GABA release at BC axons-the effect is occluded by gallamine, an M(2) receptor antagonist. Overall, muscarinic activation results in a net increase in phasic inhibitory output to the target cells. Thus, cholinergic activation through M(1)-like receptor enhances BC activity and promotes the generation of nested theta and gamma rhythms, thereby enhancing hippocampal function and associated performance.

The role of trazodone in the treatment of erectile dysfunction.

The effects of trazodone on the nocturnal penile erection were demonstrated in 14 impotent patients by Rigiscan recordings. Trazodone significantly increased the total erectile time, per cent of sleep with erection and maximum rigidity, while it had no effect on increment of tumescence size. Trazodone (150 mg to 200 mg) was administered to 35 clearly organic impotent patients in a 5-week single-blind design. Patients were evaluated by questionnaire. The study showed an improvement in 68.6 per cent of the patients receiving trazodone versus 11.4 per cent receiving placebo. In vitro, trazodone could relax rabbit corporeal smooth muscle contractions induced by exogenous norepinephrine and inhibit contractions elicited by transmural electrical stimulation of adrenergic nerve endings. The effects of trazodone on penile erection may be due to a peripheral alpha adrenoceptor antagonism and central unknown mechanism. We conclude that trazodone may prove an effective treatment for impotent patients.