An automated, handheld biosensor for aflatoxin.

A new immunoaffinity fluorometric biosensor has been developed for detecting and quantifying aflatoxins, a family of potent fungi-produced carcinogens that are commonly found in a variety of agriculture products. They have also been cited as a biological agent under weapons development. The handheld, self-contained biosensor is fully automatic, highly sensitive, quick, quantitative, and requires no special storage. Approximately 100 measurements can be made before refurbishment is required, and concentrations from 0.1 parts per billion (ppb) to 50 ppb can be determined in <2 min with a 1 ml sample volume. The device operates on the principles of immunoaffinity for specificity and fluorescence for a quantitative assay. The analytic procedure is flexible so that other chemical and biological analytes could be detected with minor modifications to the current device. Advances in electro-optical components, electronics, and miniaturized fluidics were combined to produce this reliable, small, and versatile instrument.

Centering mechanism for soft contact lenses.

A soft contact lens, because of its elasticity, can re-center itself over the cornea after it has been displaced by a blink. In this paper, a potential energy method is used to simulate the centering mechanism. Specifications for commercially available soft contact lenses and realistic eye shapes are used for the examples. With this technique we can compare the centering attributes of different lens and eye geometries.

A microplate allele-specific oligonucleotide hybridization assay for detection of factor V Leiden.

Factor V Leiden is the most common genetic risk factor for thrombosis. Currently, the determination of factor V Leiden genotype is limited to laboratories with expertise in molecular methods to develop "home brew" assays using polymerase chain reaction (PCR) to amplify genomic DNA, followed by analysis of Mnl I restriction fragments. These methods are not standardized, are labor intensive, and have low throughput. We describe a method for determination of factor V Leiden genotype using allele-specific oligonucleotide capture probes coated onto 96 well plates, requiring only a thermal cycler and a microplate spectrophotometer to perform. With an automated strip washer and plate reader, genotypes could be determined in 80 min from completion of PCR. Within-run and between-run coefficients of variation for the assay were < 10%. In all 160 cases studied, the microplate assay correctly identified the factor V genotype. The microplate oligonucleotide hybridization assay is a simple and reliable system for determination of factor V Leiden genotype. The assay offers an automatable, high-throughput alternative to current testing methodologies.

The conformity of a soft contact lens on the eye.

An axisymmetric elastic shell deformation model has been created to predict the conformity of a soft contact lens when pressed against the eye. Regions of contact and gap may be predicted, and the nonuniform reaction pressure between the lens and eye may also be found. This is important for issues like abrasion and comfort. Bending, membrane and transverse shear loads within the lens are also computed. Commercial soft contact lenses and a representative eye shape are used for the examples. We find that the uniformity of loading against the eye is strongly affected by the degree to which the lens is shaped to fit the eye, and relatively unaffected by the thickness of the lens.

Treatment of penile fibrosis with prosthetic implantation and flap advancement with tissue debulking.

PURPOSE: Even after successful penile prosthesis implantation in patients with extensive penile fibrosis, a subset will have insufficient penile length for satisfactory sexual intercourse. We report a combined surgical approach to gain additional functional length in these patients. MATERIALS AND METHODS: During the last 18 months 11 patients with extensive cavernous fibrosis underwent penile prosthesis implantation with a modified suprapubic V-Y advancement flap and lower abdominal tissue debulking. RESULTS: After prosthesis implantation the accompanying procedures allowed these patients to gain an additional 3.5 to 6.5 cm. in functional length. All patients had a functional device after a mean followup of 12 months. No prosthesis became infected and no patient required an additional flap procedure. CONCLUSIONS: This surgical approach allows patients to gain additional functional length for satisfactory intercourse after treatment of extensive penile fibrosis.

Sensitivity and specificity of the APC resistance assay in detection of individuals with factor V Leiden.

Resistance to activated protein C (APC) is the most common cause of familial thrombophilia. The partial thromboplastin time (PTT)-based test for resistance to APC has been widely employed as a screening test for this disorder. However, the utility of this test for screening is not well characterized. More than 90% of patients with resistance to APC have the G1691A mutation in factor V (factor V Leiden). The authors studied the ability of a commercial APC resistance assay to correctly identify the factor V Leiden genotype in 130 individuals. At the recommended assay cut-off value of 2, the sensitivity of the APC resistance assay was 50%, with a specificity of 98%. Increasing the cut-off value increased the sensitivity but decreased the specificity of the test. Receiver operating characteristic (ROC) curve analysis indicated that the test was of intermediate utility. There was considerable overlap in APC ratios in the range of 2 to 3 between subjects with a normal factor V genotype and heterozygotes for factor V Leiden. The authors conclude that the APC resistance assay in its present form is not a useful screening test for factor V Leiden heterozygotes. Until the performance of this assay is improved, patients should have molecular diagnostic testing performed to determine their factor V Leiden status.

A randomized crossover study using yohimbine and isoxsuprine versus pentoxifylline in the management of vasculogenic impotence.

PURPOSE: We evaluated the efficacy and safety of yohimbine and isoxsuprine or pentoxifylline in the management of vasculogenic erectile dysfunction. MATERIALS AND METHODS: A total of 20 patients diagnosed with arterial insufficiency and cavernous venous leakage by pharmacological penile duplex scanning underwent nonhormonal oral therapy. A randomized crossover study was performed using 5.4 mg. yohimbine plus 10 mg. isoxsuprine or 400 mg. pentoxifylline 3 times daily. Response to therapy was assessed by a sexual questionnaire and repeat penile duplex ultrasonography. RESULTS: No patient in either phase of the study in either group had a complete response to the oral regimen(s) and there was no improvement in the pre-injection or post-injection cavernous arterial peak systolic flow velocities or resistance indexes. CONCLUSIONS: Our study suggests that these oral agents, although well tolerated, were not effective in the management of these patients with mixed vasculogenic erectile dysfunction.

Management of nondilatable cavernous fibrosis with the use of a downsized inflatable penile prosthesis.

The basic underlying cause of inability to implant a penile prosthesis is cavernous fibrosis resulting in unsatisfactory cavernous dilation. During the last 3 years, 20 patients with severe cavernous fibrosis underwent penile prosthetic implantation with a downsized inflatable penile prosthesis, obviating the need for additional cavernous reconstruction. After a mean followup of 20 months 19 of the 20 patients had a functional device with only 1 requiring explantation for infection. We believe that this downsized penile prosthesis is a valuable addition to the urological armamentarium when considering reimplantation or implantation in a patient with intracavernous fibrosis and scarring.

Inflatable cavernosal body device: feasibility and acute safety study in the canine model.

OBJECTIVES: To determine the feasibility, safety, and acute mechanical reliability of a two-piece, implantable, inflatable cavernosal body compression device in the canine model. METHODS: Six large male dogs underwent implantation of an inflatable cavernosal compression device consisting of an inflatable cuff and a pump reservoir. The device was implanted around the corpora cavernosa excluding the corpus spongiosum near the crura. RESULTS: All devices were cycled three times a week for 2 months and radiographic evaluation found them to be mechanically reliable. Infusion cavernosometry with inflation of the device demonstrated greater than a 100% increase of intracorporeal pressure from baseline levels. Histologic assessment showed no adverse tissue effects on the penile tissue underlying the cuff or remote from the cuff in the penis and there was no development of distant thromboembolism. CONCLUSIONS: The results from this study will form the basis of long-term canine studies to investigate physiologic changes on the canine erection and chronic safety and reliability of the device.

The use of flutamide in hormone-refractory metastatic prostate cancer.

In a recent intergroup study under the auspices of the National Cancer Institute, 603 eligible patients with newly diagnosed disseminated adenocarcinoma of the prostate were prospectively randomized in a double-blinded clinical trial to receive either a gonadotropin-releasing hormone analogue (leuprolide) and a nonsteroidal antiandrogen (flutamide) or leuprolide and placebo. Of the 603 eligible patients, 300 were in the leuprolide and placebo arm and 303 were in the leuprolide and flutamide arm. At the time of disease progression, the code was broken: Those patients in the placebo arm were given the opportunity to receive flutamide, and the patients in the flutamide arm were treated at their physician's discretion. There was no survival time distribution difference, based on survival measured from the progression data, between the patients who were received flutamide after progression and those who were treated at their physician's discretion after progression. Furthermore, the addition of flutamide to leuprolide at the time of disease progression resulted in a survival-time distribution that is similar to other treatments of hormone-refractory prostate cancer.

The titanium intraprostatic stent: the United States experience.

This multicenter, cooperative study represents the initial United States experience using an expandable, titanium intraprostatic stent in 68 patients (60 to 93 years old). The stents were inserted under direct vision and expanded to 33F using a balloon catheter. All patients had a symptom score analysis, and underwent measurement of peak urine flow and rate and post-void residual urine volume as part of the initial evaluation. Patients were seen at approximately 1, 3, 6 and 18 months after stent insertion (mean followup 16 months). Of the 68 patients 38 presented in urinary retention. The type of anesthesia used included general anesthesia in 6 patients, spinal or epidural anesthesia in 24, intravenous sedation in 20 and intraurethral lidocaine only in 18. All patients were able to void spontaneously within 36 hours after stent insertion. Symptom scores decreased from 16.8 to 3.9, 6.3, 5.0, 5.7 and 3.2 at approximately 1, 3, 6, 12 and 18 months, respectively. Peak urine flow rate increased from 3.9 to 13.8, 11.5, 11.2, 12.4 and 14.4 ml. per second at approximately 1, 3, 6, 12 and 18 months, respectively. Post-void residual urine volume decreased from 74.4 to 30.1, 29.2, 19.8 and 40.2 ml. at approximately 1, 3, 6 and 12 months, respectively. Of the initial 68 patients 5 died of the underlying disorder (all voiding satisfactorily with the stent in place) and 17 underwent uneventful stent removal (10 for technical failure and 7 for treatment failure). Technical failures were secondary to either inaccurate positioning or improper stent sizing. Of the 58 patients with proper placement of the stent and no technical failures 46 (79%) had improvement in symptom scores and urine flow rate. Transient hematuria was noted in 43 patients (63%) and usually resolved within 48 hours. None of the 6 urinary tract infections (9%) was recurrent. In conclusion, the titanium intraprostatic stent, when properly placed, is a promising therapeutic alternative to prostatectomy or long-term catheterization in high risk obstructed patients or those in urinary retention. Studies are currently in progress to determine the long-term efficacy of this therapeutic modality.

Workshop summary: approaches to radical prostatectomy.

The retropubic approach has recently become the method of choice for radical prostatectomy. This has been particularly evident since the 1970s, when open staging lymphadenectomy became an important part of the diagnostic workup, as both procedures could be carried out concurrently via the anterior approach. However, the development and rapidly increasing use of laparoscopic lymphadenectomy may signal a return to the perineal approach in certain cases. Alternatives to radical prostatectomy, including radiotherapy and interstitial brachytherapy, may also have their place. The audience was asked to comment on their own practices and the factors that would influence their decisions.

Total androgen blockade: the United States experience.

Maximal androgen blockade may improve the effectiveness of treatment of prostate cancer. To test this hypothesis we conducted a randomized, double-blind trial in patients with disseminated and previously untreated prostate cancer (stage D2). All patients (n = 603) received leuprolide, 1 mg/day s.c. in combination with either placebo (n = 300) or flutamide 250 mg p.o. t.i.d. (n = 303). The median progression-free survival times were estimated at 14 months for the leuprolide plus placebo group and 17 months for leuprolide plus flutamide patients: median times for overall survival were 29 vs. 35 months, respectively. Patients with minimal disease and good performance status did particularly well on combination therapy. Median progression-free survival for this subgroup was 19 months for leuprolide plus placebo patients vs. 48 months for patients on combined therapy (p = 0.035) Flutamide appeared to reduce the disease flare associated with leuprolide monotherapy. Combined androgen blockade with leuprolide and flutamide is superior to leuprolide treatment alone in patients with disseminated prostate cancer.

Penile venous ligation surgery for the management of cavernosal venous leakage.

Forty-one patients underwent penile venous ligation surgery for pure cavernosal venous leakage diagnosed by infusion cavernosometry and cavernosography. Before surgery, arterial integrity was assessed by pelvic angiography, and all patients were found to have a normal penile arterial system. The patients were divided into two groups on the basis of the type of venous operation performed. The overall complete-potency success rate was 46% (19 of 41 patients). Postoperative complications were minimal. Our experience shows that penile venous surgery remains an acceptable option for treatment of carefully selected patients with documented pure cavernosal venous leakage of a mild degree who have no evidence of arterial insufficiency and who do not prefer, or are not suitable for, other medical or surgical treatment options. Patients who had more severe degrees of cavernosal venous leakage had a poor result from this procedure. For patients with moderate to severe venous leakage, we now perform a combined surgical procedure, deep dorsal vein arterialization and venous ligation.

A rationale for the use of non-steroidal anti-androgens in the management of prostate cancer.

Flutamide is a non-steroidal anti-androgen which has been used to treat prostate cancer. Results to date indicate that flutamide is as effective as other conventional therapy. It has only moderate activity in patients in whom conventional hormonal therapy has previously failed, but appears to be beneficial when combined with an LHRH agonist.

National Cancer Institute study of luteinizing hormone-releasing hormone plus flutamide versus luteinizing hormone-releasing hormone plus placebo.

A randomized, double-blind trial in patients with disseminated, previously untreated prostate cancer (stage D2) was designed to test the hypothesis that maximal androgen blockade improves the effectiveness of the treatment of prostatic cancer. Six hundred three men received leuprolide in combination with either placebo or flutamide, and were followed for a minimum of 5 years. The 303 patients randomly assigned to receive leuprolide and flutamide had a longer progression-free survival and an increase in the median length of survival compared with the 300 patients receiving leuprolide plus placebo. Differences between the treatments were particularly evident for men with minimal disease and good performance status.

The incidence of Peyronie's disease in Rochester, Minnesota, 1950 through 1984.

Peyronie's disease was diagnosed in 101 male residents of Rochester, Minnesota between 1950 and 1984. Mean patient age at diagnosis was 53 years. The average age-adjusted annual incidence rate of 25.7 and a prevalence rate of 388.6 per 100,000 male population were noted. The steady increase in incidence with time may reflect an increasing tendency to obtain medical help. However, the possibility of a true increase in the incidence rate cannot be ruled out. An effort was made to identify possible risk factors and other disease associations. Rheumatoid arthritis and hypertension were more common among the patients compared to the Rochester population. In contrast, no excess of diabetes mellitus was observed among patients with Peyronie's disease.

MR imaging of fetal anomalies.

MR imaging can be used to confirm the presence of most gross fetal anomalies detected by sonography in the second and third trimesters. The MR imaging findings in 25 cases of fetal anomalies first identified on sonography are illustrated.

[Use of photodynamic therapy in the treatment of refractory carcinoma in situ]. / Die Anwendung der photodynamischen Therapie zur Behandlung des therapieresistenten Carcinoma in situ.

Photodynamic therapy (PDT) is a new and innovative approach to the treatment of malignant disease. This treatment modality involves administration of a photosensitizer, which is retained in malignant tissue, followed by exposure of that tissue to light corresponding to one of the absorption bands of the drug, with resultant cell death. Several photosensitizers are currently under study, but haematoporphyrin derivative (HPD) is the drug that has been used almost exclusively in clinical urological trials. Both direct and indirect methods have been used to document the preferential concentration or retention of HPD in malignant urothelium. Although this drug is not a perfect tumour localization aid, it is perhaps the best that has thus far been studied for transitional cell carcinoma of the bladder. Over the past decade of investigation, PDT has become established to the point that it is now being tested in phase II and III trials against standard and approved drugs for the treatment of noninvasive transitional cell carcinoma of the bladder.

Malignant potential of the cryptorchid testis.

A follow-up study of 224 male patients from Rochester, Minnesota, diagnosed with cryptorchidism during the period from 1935 through 1974 was conducted to assess the frequency of subsequent testicular neoplasms. Age-specific rates for testicular neoplasm in this community were used to estimate an expected number for comparison with that observed. Two malignant testicular neoplasms have occurred in this cohort; thus, the standardized morbidity ratio was 11.4 (95% confidence interval, 1.4 to 41.1). Of the 158 patients born in the community, 11% were known to have birth weights of less than 2,500 g, approximately twice the expected occurrence. Increased risks were also noted for inguinal hernia, hypospadias, Down's syndrome, cleft lip or palate (or both), clubfoot, and congenital heart disease, for which the standardized morbidity ratios were 3.6, 4.7, 17.8, 11.3, 11.7, and 2.7, respectively. The increased risk for malignant neoplasms observed in this cohort of patients with cryptorchidism is consistent with that found in earlier studies.