New imaging techniques in prostate cancer

Correct staging of prostate cancer at initial diagnosis, as well as accurate staging and tumor localization with biochemical recurrence, remains generally inaccurate with current imaging techniques. Newer modalities are being investigated to accurately identify patients with prostate cancer at different stages of disease. Identification of locally recurrent disease or distant metastasis at the time of biochemical failure after local therapy will help guide treatment options and avoid potentially toxic salvage therapies in patients who will not benefit. A review of prostate cancer imaging literature over the past 12 months was performed to identify emerging imaging modalities that may be beneficial in the management of prostate cancer. Enhanced transrectal ultrasonography modalities, including ultrasound contrast agents, color and power Doppler, and elastrography, have demonstrated incremental benefit when combined with standard grayscale ultrasonography to accurately target and diagnose prostate cancer. Endorectal MRI, with contrast enhancement and spectroscopic imaging, shows promise in the initial staging of prostate cancer prior to local therapy. The use of positron-emission tomography scan for prostate cancer remains to be defined, but may help delineate the site of recurrence with biochemical failure after local therapy. Several new imaging modalities show promise for the evaluation of the patient with prostate cancer. Enhanced ultrasonography techniques may prove to be more accurate in diagnosing prostate cancer over standard gray-scale ultrasonography. Accumulating evidence supports the use of endorectal MRI and spectroscopy to help treatment planning with either surgical or radiotherapeutic approaches. Although intriguing, the available data for positron-emission tomography in prostate cancer remains too shallow to advocate routine use.     

The nitric oxide pathway in pre-eclampsia: pathophysiological implications

Pre-eclampsia, one of the most significant health problems inhuman pregnancy, complicates 6-7% of all gestations and is theleading cause of fetal growth retardation, infant morbidityand mortality, premature birth and maternal death. Recent researchimplicates free radicals in the pathophysiology of pre-eclampsia.This review covers the biochemistry of nitric oxide (NO) andpossible interactions with other free radicals. Studies in therat show that pregnancy is associated with enhanced productionand responsiveness to NO in both reproductive tissues and bloodvessels. Rats infused with N^G-nitro-L-arginine methyl ester(L-NAME, a NO synthase inhibitor) have been used as an animalmodel of pre-eclampsia, and the effects of steroid hormoneson blood pressure in this model have been tested. Results suggestthat pre-eclampsia may be a state of NO deficiency. However,in humans there seem to be contradictions regarding the involvementof NO in maternal adaptation to pregnancy. It is suggested thatNO may be one of several systems that act in concert to maintaina symbiotic relationship between mother and fetus. However,the input of each system may be genetically determined.     

Surgical sperm retrieval and intracytoplasmic sperm injection as treatment of obstructive azoospermia

Male genital tract obstructions may result from infections, previous inguinal and scrotal surgery (vasectomy) and congenital bilateral absence of the vas deferens (CBAVD). Microsurgery can sometimes be successful in treating the obstruction. In other cases and in cases of failed surgical intervention, the patient can be treated by microsurgical or percutaneous epididymal sperm aspiration (MESA, PESA) or testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). We present the results of 39 ICSI procedures for obstructive azoospermia in 24 couples. The aetiology of the obstruction was failed microsurgery in 11 patients, CBAVD in nine and genital infections in four. Sperm retrieval was accomplished via MESA in four cases, PESA in 18 cases and via TESE in 11 cases. TESE was only applied when PESA failed to produce enough spermatozoa for simultaneous ICSI. In six patients, the ICSI procedure was performed with cryopreserved spermatozoa after an initial PESA procedure. Fertilization occurred in 47% of the metaphase II oocytes; embryo transfer was performed in 92% of procedures and resulted in a clinical pregnancy in 13/39 procedures. Ongoing pregnancy was achieved in 10/39 procedures. One pregnancy was terminated early after prenatal investigation showed a cytogenetic abnormality (47,XX+18, Edwards syndrome). The other nine pregnancies resulted in the live birth of 10 children, without any congenital abnormalities. Epididymal and testicular retrieved spermatozoa were successfully used for ICSI to treat obstructive azoospermia, and resulted in an ongoing pregnancy in 10 of 24 couples (41.6%) after 39 ICSI procedures, a success rate of 25.6% per treatment cycle and of 27.7% per embryo transfer.      

Comparing food intake using the Dietary Risk Assessment with multiple 24-hour dietary recalls and the 7-Day Dietary Recall

The Dietary Risk Assessment (DRA) is a brief dietary assessment tool used to identify dietary behaviors associated with cardiovascular disease. Intended for use by physicians and other nondietitians, the DRA identifies healthful and problematic dietary behaviors and alerts the physician to patients who require further nutrition counseling. To determine the relative validity of this tool, we compared it to the 7-Day Dietary Recall (an instrument developed to assess intake of dietary fat) and to the average of 7 telephone-administered 24-hour dietary recalls. Forty-two free-living subjects were recruited into the study. The 7-Day Dietary Recall and DRA were administered to each subject twice, at the beginning and the end of the study period, and the 24-hour recalls were conducted during the intervening time period. Correlation coefficients were computed to compare the food scores derived from the 3 assessment methods. Correlations between the DRA and 7-Day Dietary Recall data were moderate (r = .47, on average, for postmeasures); correlations between the DRA and 24-hour recalls were lower. The ability of the DRA to assess dietary fat consumption and ease of administration make it a clinically useful screening instrument for the physician when counseling patients about dietary fat reduction.     

The optical properties of the anterior segment of the eye: implications for cortical cataract.

Epidemiological studies have correlated cortical cataract with exposure to light and have suggested that this is due primarily to relatively short wavelengths of ultraviolet radiation (UV-B). In addition, some cellular and animal models also implicate UV-B. In order to evaluate the likely role of different wavelengths of light in the etiology of cortical cataracts, the optical characteristics of several animal models were ascertained and compared to the primate. This study shows that the mouse model absorbs UV-B almost exclusively whereas other animal models such as the rabbit and the guinea pig also contain chromophores that absorb UV-A. The absorptive characteristics of the human lens varies drastically with age. The young lens absorbs primarily UV-A, whereas with age, there are increases in absorptions at 320 nm and out to wavelengths as long as 550 nm. By sectioning human lenses it was found that these changes in absorption properties increased toward the central and the nuclear regions.These absorptive characteristics were then compared to the amount of light reaching the surface of the lens. It was found that UV-B is a minor component of total energy reaching the surface of the human lens and old human lens proteins absorb 2 orders of magnitude more UV-A and visible light than UV-B. It is concluded that it is premature to exclude UV-A or even visible light in the etiology of human cortical cataracts.     

Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy.

PURPOSE: To assess the efficacy of the marine-derived alkaloid ecteinascidin 743 (ET-743) in patients with soft tissue sarcomas that progressed despite prior conventional chemotherapy and to characterize the pharmacokinetic profiles of ET-743 in this patient population. PATIENTS AND METHODS: Thirty-six previously treated soft tissue sarcoma patients from three institutions received ET-743 as a 24-hour continuous intravenous (IV) infusion at a dose of 1,500 microg/m(2) every 3 weeks. Pharmacokinetic studies were also performed. Patients were restaged every two cycles for response by objective criteria. RESULTS: Objective responses were observed in three patients, with one complete response and two partial responses, for an overall response rate of 8% (95% CI, 2% to 23%). Responses were durable for up to 20 months. Two minor responses (43% and 47% tumor reduction) were observed, for an overall clinical benefit rate of 14%. The predominant toxicities were neutropenia and self-limited transaminitis of grade 3 to 4 severity in 34% and 26% of patients, respectively. The estimated 1-year time to progression and overall survival rates were 9% (95% CI, 3% to 27%) and 53% (95% CI, 39% to 73%), respectively. The maximum observed plasma concentration and total plasma clearance of ET-743 (mean +/- standard deviation), 1.04 +/- 0.48 ng/mL and 35.6 +/- 16.2 L/h/m(2), respectively, were consistent with previously reported values from phase I studies of the drug given as a 24-hour IV infusion. CONCLUSION: ET-743 is a promising new option for the management of several histologic subtypes of sarcoma. Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy. Additionally, the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent.