Transurethral needle ablation (TUNA) of the prostate using low-level radiofrequency energy: an animal experimental study.

Transurethral needle ablation of the canine prostate using low level radiofrequency energy was examined for efficacy and safety in a two-stage experimental study. Eleven mongrel dogs were treated via the bladder neck and prostatic urethra using a specially designed catheter through which needle antennas were advanced into the prostatic tissue. A radiofrequency energy source was connected to the catheter and used to create tissue ablation. In the first 5 dogs this was found to be feasible. Necrotic lesions were created around the needle antennas. Typically, lesions were 1 cm in diameter and conical in shape. The actual size of the lesion was directly related to power level used, time of ablation and length of needle deployment. In the next 6 dogs temperatures were simultaneously measured in the prostatic urethra and rectum. The dogs were sacrificed 0, 2, 2, 14, 28 and 30 days following the experiments and the bladder, prostate and anterior rectal wall were removed en bloc and examined macroscopically and histopathologically for any changes. It was found that urethral temperatures increased to 46.1 degrees C on the average while rectal temperature did not rise during the entire experiment. The lesions found in the prostate were similar to those found in the first 5 dogs. No macroscopic or histopathologic changes were noted at the bladder base, anterior rectal wall or in the distal prostatic urethra. It was concluded that prostatic tissue ablation in the canine model can be achieved safely and could justify the start of human trials.

Needle ablation using radio frequency current as a treatment for benign prostatic hyperplasia: experimental results in ex vivo human prostate.

Transurethral needle ablation of the prostate using low level radiofrequency (RF) energy was investigated in a human ex vivo model. RF power applications at a variety of power levels for various treatment times elicited marked thermal lesions of consistent sizes in prostatic adenomas. Tissue temperature was found to be the fundamental lesioning parameter. Lesions were created whenever tissue temperature exceeded 45 degrees C. Lesion size correlated with RF power delivery and electrode length. Monitoring of the tissue impedance assisted in controlling efficacious lesioning. RF power applications of 5-7.5 W for 3 min are suggested as the 'ideal' setting to treat human prostatic adenomas, taking into consideration the lesion size and time to achieve ablative temperatures.

Transurethral needle ablation (TUNA): thermal gradient mapping and comparison of lesion size in a tissue model and in patients with benign prostatic hyperplasia.

A new device has been development for treating benign prostatic hyperplasia (BPH) that is performed as an outpatient procedure. the device (transurethral needle ablation or TUNA) employs needles that deliver low-level radiofrequency (RF) power locally at high temperature to ablate hyperplastic prostate tissue. During the TUNA procedure the temperature proximal to the needle tips is measured with thermocouples within the needle's protective shields and urethral temperature is measured via a thermocouple contained within the catheter tip. Tissue impedance is also measured by the TUNA catheter since it is well known from other thermal treatment methods that thermal destruction of prostatic tissue depends upon a particular prostate's tissue composition and thermoregulation. Because of this variation in prostates, a nomogram guide for setting the TUNA device was created using a turkey breast tissue model. Lesion sizes created at particular settings in the turkey breast model were similar to those created at the same settings in patients with BPH. In addition, local thermal gradients within the TUNA lesions were visualized and mapped using an infrared thermal imaging system which demonstrated that central lesion temperature with the device is approximately 80-100 degrees C.

Transurethral needle ablation (TUNA): safety, feasibility, and tolerance of a new office procedure for treatment of benign prostatic hyperplasia.

Many attempts have been made to develop a method for treating benign prostatic hyperplasia (BPH) that is minimally invasive, efficacious, and low cost. The transurethral needle ablation (TUNA) device has recently been developed to treat BPH by selectively ablating hyperplastic prostatic tissue. A special catheter incorporates needles that deliver low-level radiofrequency power directly to a very localized area of the prostate. The needles have adjustable shields to protect the urethra if desired or necessary. It is positioned via transrectal ultrasound or direct vision. A pilot study was performed in patients to evaluate TUNA feasibility via histopathological measurement of thermal lesion size and TUNA safety by: (1) monitoring urethral and rectal temperatures; (2) assessing the ability to localize lesions, and (3) determining patient tolerance of the procedure without anesthesia. Twenty patients were treated using TUNA prior to scheduled retropubic prostatectomy. The surgical prostatic specimens were recovered from 1 day to 1 month after TUNA, were step-sectioned, and examined histologically. Patients were 68 years old on average with prostate weight varying from 14 to 88 g. The TUNA procedure averaged 27 min, 4 lesion treatments per prostate, and 4-15 W of power applied for 3 min. Proximal lesion temperature was about 40-50 degrees C with central lesion temperatures of about 80-100 degrees C. Urethral temperature averaged 37-42 degrees C and rectal temperature remained unchanged. Macroscopic examination of the specimens demonstrated localized lesions averaging 12 x 7 mm. Microscopic examination showed larger lesions of extensive coagulative necrosis averaging 30 x 15 mm. Specific immunohistochemical staining showed destruction of all tissue components.(ABSTRACT TRUNCATED AT 250 WORDS)

Significantly improved peripheral intravenous catheter performance in neonates: insertion ease, dwell time, complication rate, and costs.

A prospective, randomized, controlled study was performed in neonates in an intensive care nursery to compare the performance of a peripheral intravenous catheter made of Aquavene material (test catheter) with that of a conventional peripheral catheter made of Teflon material (control catheter). Aquavene is a newly developed biomaterial that softens and expands on contact with body fluids. A total of 105 catheters (50 test and 55 control) were inserted in 63 neonates. The median time to a catheter-related complication was 3.60 days for the test catheters and 1.75 days for the control catheters (p = 0.0007). Infiltration rate for the test catheters was 56% as compared with 78% for the control catheters (p = 0.03). The test catheters provided fewer catheter-related complications (p = 0.006), with 34% of the test catheters reaching end of therapy as compared with 9% of the control catheters (p = 0.004). On average, 1.8 test catheters were used per insertion versus 2.3 control catheters (p = 0.08). The test catheters were rated easier to insert (p = 0.05), with a shorter time required for insertion. Because of improved performance, cost savings were realized with the test catheters after the first day of therapy, even though the per unit cost of the test catheter was greater. These data indicate that the test catheter, made of Aquavene material, is superior to the Teflon catheter for peripheral intravenous therapy in neonates.

New peripherally inserted midline catheter: a better alternative for intravenous antibiotic therapy in patients with cystic fibrosis.

A study was performed on outpatients with cystic fibrosis (CF) to evaluate the performance of an over-the-needle peripherally inserted midline catheter for the delivery of 2-week courses of antibiotic therapy. The midline is a 7-inch catheter inserted in the antecubital region with the tip located in the axillary region. It is made of a newly developed biomaterial that softens and expands upon contact with body fluids. The hypotheses for the study were that the midline catheter: 1) is useful for intermediate-length therapies; 2) can prevent multiple 3-day conventional peripheral catheter restarts; 3) can prevent or delay the use of more invasive central devices; 4) is comfortable for patients; and 5) is economical. A total of 41 midlines were inserted in 27 patients with an average age and weight of 22 years and 109 pounds, respectively. Prior to this study implanted ports and primarily conventional short peripheral catheters were used to administer I.V. therapy to these patients; fifty percent of these short peripheral catheters failed within 2.6 days. At 2 weeks of dwell, 80% of the midline catheters placed in these patients were still indwelling. Also, 80% of all midline catheter removals were for non-catheter-related reasons. There were no cases of midline catheter phlebitis. In contrast, the phlebitis rates published for peripherally inserted central catheters (PICCs) and conventional short peripheral catheters at 7 days of dwell are 20% and greater than 51% respectively. The midline catheters were comfortable and well liked by most patients and became more economical than conventional peripheral catheters for therapies lasting approximately 6 days through 1 to 2 months.(ABSTRACT TRUNCATED AT 250 WORDS)

A new method for assessing right-sided heart pressures using encapsulated microbubbles--a preliminary report.

A new noncatheter method for measuring pressures of the right side of the heart uses specially manufactured microbubbles of carbon dioxide injected into the peripheral venous system. Sudden expansion of these bubbles in the cardiac chambers causes bubble oscillations at a frequency that is primarily a function of surrounding pressure. The oscillations are recordable by a microphone on the chest wall. The preliminary experience has been in dogs and further development is needed before we can begin clinical testing of the method. In its current form, the potential for measuring higher systolic pressures seems better than that for lower diastolic pressures.

Varying bioactive to immunoactive ratios of the human chorionic gonadotropin-like substance present in normal human tissues.

To further characterize the hCG-like substance found in normal nonpregnant human tissues, we compared the biological (B) and immunological (I) activities of the substance in extracts of 40 nontrophoblastic tissues and 7 placentas. B was measured in an in vitro mouse testicular interstitial cell bioassay, and I was measured in the beta hCG RIA. Highly purified hCG (CR 119) was used as a standard. B was detected in 92% of the nontrophoblastic nonpituitary tissues. Parallelism between serial dilutions of extracts and the hCG standard was found for 75% of the pituitary extracts, 86% of the placental extracts, and 53% of the other tissues. The correlation between B and I activities in the nontrophoblastic nonpituitary tissues was good (r = 0.8; P less than 0.001). Preincubation of the tissue extracts with anti-hCG serum before bioassay significantly reduced the B activity. There was wide variation in the B to I ratio between tissues and within the same tissues from different individuals. A B to I ratio less than 1 was found in 50% of the tissues, excluding placenta and pituitary, and may have been due to the presence of incomplete or altered hCG molecules, which are immunologically active but have reduced B activity.

Characterization of antihuman chorionic gonadotropin serum antibody appearing after ovulation induction.

After repeated im courses of menopausal gonadotropins and hCG, a factor was found in a woman's serum which preferentially bound the intact hCG molecule (nanograms or milliinternational units required for 50% displacement of [125I] hCG: hCG, 9.2 ng; APL, 74 mIU; Pergonal, 400 mIU; LER 960, 900 ng; and FSH and TSH alpha-subunits, hCG beta-subunit, and LH beta-subunit, greater than 1000 ng). This factor had a low affinity (Ka = 5.8 X 10(9) liters/M) and high capacity (binding capacity, 5.5 X 10(-11) M/liter) for hCG, was isolated with the immunoglobulin G fraction of the patient's serum, and coeluted with immunoglobulin G from a Sepharose CL-6B-200 column. Preincubation of hCG with this fraction did not reduce the in vitro biological activity of the hCG in the hypophysectomized rat ventral prostate weight assay. Similarly, there was no gonadal resistance to hCG in the patient, since ovulation could still be induced with hCG, and both progesterone and 17-hydroxyprogesterone levels as well as duration of the luteal phase increased after repeated hCG injections. This serum factor prolonged the half-life of injected hCG in the patient's circulation (t 1/2 = 9.4 days in patient vs. 1.3 days in controls). The titer of the factor transiently decreased with the exogenous administration of hCG. No binding of the serum factor to human placental tissue could be demonstrated by immunohistochemical techniques. Thus, this factor behaves similarly to the antibodies frequently found after the injection of other polypeptide hormones, in that it serves as a high capacity reservoir of the hormone but does not significantly reduce its biological activity. These results also indicate that the factor requires the intact tertiary structure of the hCG molecule for immune recognition.

An evaluation of 10 kits for determination of human choriogonadotropin in serum.

We compared 10 commercially available radioimmunoassay kits (American Diagnostics, Becton Dickinson, BioGenex, Clinical Assays, Hybritech, Leeco, Mallinckrodt, Microanalytic, Nuclear Medical Systems, and Radioassay Systems) for determination of human choriogonadotropin (hCG), using serum pools, hCG CR119 (NIH), 2nd I.S. (who), and 1st I.R.P. (who). Criteria were ease of performance, total assay time, sensitivity, potency, and parallelism as compared with reference standards and results for 15 serum pools. The Mallinckrodt kit exhibited the best overall performance, with good low-concentration sensitivity, parallelism with two of the three reference preparations, and good clinical correlation as compared with the reference kit from NIH. Because the antibodies used in the kits are occasionally changed by the manufacturers, these results are necessarily valid only for kits that include reagents identical to those in the kits that we tested.

PIP: As a result of better understanding of the biochemical and structural natures of the human choriogonadotropin (hCG) molecule and development of monoclonal antibody techniques, manufacturers of pregnancy determination kits have been able to produce antibodies against hCG or beta-hCG that are more sensitive and specific. This study evaluated 10 commercially available radioimmunoassay kits (American Diagnostics, Becton Dickinson, BioGenex, Clinical Assays, Hybritech, Leeco, Mallinckrodt, Microanalytic, Nuclear Medical Systems, and Radioassay Systems) for determination of hCG and compared the antisera in these kits with the National Institutes of Health (NIH) reference antibody SB-6. Serum pools, hCG CR119 (NIH), The World Health Organization (WHO) 2nd International Standard (IS), and the WHO 1st International Reference Preparation (IRP) were used for calibration. Criteria were ease of performance, total assay time, sensitivity, specificity, and parallelism as compared with reference standards and results for 15 serum pools. The Mallinckrodt kit exhibited the best overall performance, with good low-end sensitivity at the 80% binding dose, parallelism with 2 of the 3 reference preparations (hCG CR119 and WHO 1st IRP), and good clinical correlation against the NIH reference kit. The kit from Leeco also performed well in the clinical correlation category, but it failed the parallelism tests against all the reference standards. Because the antibodies used in these kits are continually changed by the manufacturers, these results are valid only for the kits that include reagents identical to those in the kits tested in this study. Caution should also be exerted in interpreting borderline titers of hCG (5-20 IU/L in serum relative to the 2nd IS) as indicative of pregnancy. Since samples with titers in this range are positive for hCG but not necessarily for pregnancy, 2nd specimens should be requested 1 week later.

Ultrasonic contrast enhancement of tissue by encapsulated microbubbles.

Pilot studies have shown that gelatin encapsulated microbubbles (GEM) are readily demonstrable ultrasonic contrast agents. GEM injected into hepatic and renal blood vessels resulted in increased echogenicity of the parenchyma in normal rabbits. VS carcinoma implanted in the rabbit liver and kidney showed significantly different echogenicity from that of normal parenchyma following GEM injection. Echogenic bubbles were delivered to different regions by varying the size of GEM.

Experimental brain abscess: enhanced sonography and pathologic correlation.

A new sonographic contrast agent, gelatin-encapsulated nitrogen microbubbles, was introduced intraarterially to enhance the high-resolution sonographic scan of an experimental brain abscess. The echogenicity produced by the microbubbles correlated closely to the site and distribution of abscess neovascularity. The contrast agent aided in the detection of small necrotic centers in the late stages of abscess evolution when these centers were not visualized on noncontrast sonograms. The echogenic effect of the microbubbles was maximum immediately after injection; it decreased by 5 min and had virtually disappeared at 15 min.

Interrelationships of human chorionic gonadotropin, human placental lactogen, and pregnancy-specific beta 1-glycoprotein throughout normal human gestation.

Human chorionic gonadotropin (hCG), human placental lactogen (hPL), and pregnancy-specific beta 1-glycoprotein (PSBG) were measured by radioimmunoassay in 270 samples of serum from women with uncomplicated pregnancies. All three proteins were significantly correlated with each other in individual samples of serum and with the estimated trophoblastic mass during the first trimester. No significant correlation could be demonstrated between the concentrations of hCG and PSBG in maternal serum during the second or third trimesters or between the concentrations of hCG and hPL during the second trimester. Levels of PSBG and hPL in serum were significantly correlated throughout all three trimesters. These findings suggest that the secretion of hCG, hPL, and PSBG may be regulated by similar control mechanisms during the first trimester of pregnancy. However, after this period, the factors that modulate the production of hCG differ from those that regulate the production of hPL and PSBG.

Maternal serum human chorionic gonadotropin concentrations and fetal sex prediction.

The feasibility of using maternal serum human chorionic gonadotropin (hCG) concentrations for prenatal sex prediction was examined. hCG was mesured in 822 serum samples from 560 women with uncomplicated pregnancies. Significantly higher hCG concentrations were found in the serum of women bearing female fetuses than in the serum of women bearing male fetuses during the third trimester, especially during the 10th lunar month. The data were utilized to construct probability graphs for fetal sex prediction based upon a single maternal serum hCG determination during the third trimester and during the 10th lunar month. However, the utility of these graphs is limited by the small proportion of pregnant women with serum hCG concentrations that were high or low enough to allow a prediction with high probability.

Widespread distribution of a chorionic gonadotropin-like substance in normal human tissues.

Recent studies have demonstrated that the normal human testes, colon, and liver contain a substance that resembles hCG. To extend these findings, we examined aqueous extracts of a variety of normal human tissues for the presence of this material. The beta-hCG RIA, rat Leydig cell radioreceptor assay, and a newly developed, highly specific hCG RIA were used to measure hCG activity in a serial dilutions of the extracts. Detectable concentrations of the hCG-like material were found in 146 of the 149 individual tissue samples studied. Parallelism was noted between the hCG standard and serial dilutions of extracts of testis, ovary, pituitary, lung, liver, kidney, spleen, stomach, placenta, and some small intestinal tissue samples in the beta-hCG RIA, radioreceptor assay, and the highly specific hCG RIA. An absence of parallelism was found between extracts of nonpituitary tissues and LH in the beta-LH RIA. Pancreatic extracts altered the [125I]hCG used as the labeled ligand in these assays, which led to spurious results. Chromatography of the extracts on Concanavalin A-Sepharose columns revealed that the hCG-like materials from different tissues varied widely in their adsorbtion to Concanavalin A, possibly reflecting differences in their carbohydrate contents. These results indicate that an hCG-like substance is widely distributed throughout normal human tissues and further supports the concept that the fetal genome responsible for hCG production is not completely suppressed in adult tissues.

Serum glycoprotein hormone alpha subunit levels in patients with cancer.

The serum glycoprotein hormone alpha subunit concentration was measured in 957 nonpregnant patients with benign disorders and 683 patients with unselected malignancies. Postmenopausal women had significantly higher alpha levels than premenopausal women or men. When the patients were subdivided according to age, sex or disease sites, significant population differences were found for women less than 50 years of age and patients with cancers of presumed neural crest origin. However, individual serum alpha levels in patients with benign disorders or malignancies demonstrated considerable overlap. No population differences in serum alpha concentrations were demonstrated between patients grouped according to stage of disease, suggesting that serum alpha were not directly related to tumor burden. Similarly, there was no statistical association between clinical improvement or deterioration and change in the serum alpha subunit concentration. These results indicate that measurement of the glycoprotein hormone alpha subunit concentration in the serum is not useful for screening patients for cancer or for monitoring the clinical course of patients with the vast majority of cancers.