Effects of feeder cells (human cancer cell lines) on the development of mouse embryos by co-culture

The participation of apical membranes of uterine epithelial cells in the process of blastocyst adhesion makes them an interesting object in the study of changes occurring during early pregnancy. In the study of these changes alkaline phosphatase (AIP), a typical brush border enzyme, was chosen for demonstration with the scanning electron microscope (SEM) by means of a backscatter detector. Thus the temporal and spatial pattern of enzyme activity on the uterine luminal surface was made visible with lead salt procedures. AIP activity was shown to be located on apical membranes and microvilli of endometrial epithelial cells with high activity on day 2 of pregnancy decreasing to virtually no activity on day 5. This decrease in overall AIP activity was shown to be asymmetrical with respect to the uterine cavity. It begins on the antimesometrial half of the uterine lining on day 2. A distribution pattern demarcating a presumptive implantation site along the uterine horn was not found. However, on day 5 of pregnancy, a characteristic pattern of surface folds was found, dividing the uterine horn into 'implantation segments'. In addition, SEM investigation revealed a marked variation of AIP activity from one individual cell to the next on day 2 of pregnancy resulting in a mosaic-like pattern. This pattern is lost with the decrease of AIP activity on day 5. Thus heterogeneity of uterine epithelial cells in AIP activity is apparently a feature of nonreceptive epithelium in contrast to the homogeneous epithelium on day 5. It is proposed that epithelial cell homogeneity could be a marker for uterine receptivity.     

Case report: fracture of central intrauterine tube following insertion of high dose rate intracavitary applicator

We present a unique complication of high dose rate afterloading intrauterine brachytherapy occurring in a patient requiring treatment for carcinoma of the uterus. A high dose rate afterloading intrauterine insertion was performed under general anaesthetic, following which routine check films revealed that the central uterine tube had fractured at the level of the cervical os.     

Metabolism of oxytocin in rat uterus and placenta in late gestation

Concentrations of oxytocin (OT) peptide increase in rat uterine tissues at the time of parturition. We have measured the rate of OT metabolism in these tissues in late gestation to determine whether a decrease in OT catabolism is responsible for the increase in OT concentrations. Uterine and placental tissues were obtained from groups of rats at Days 16, 19, 21, 21.5, 22, and after delivery of the first pup. Delivery usually occurs in the early afternoon of Day 22. Some animals were treated with the estrogen receptor blocker tamoxifen, which will delay parturition by approximately 24 h. Cytosolic and microsomal preparations obtained using ultracentrifugation were incubated with radiolabeled OT. Metabolites were separated using HPLC, and enzyme kinetic parameters were calculated. OT was actively metabolized in both uterine and placental tissues. Total oxytocinase activity was similar in the two tissues. In uterine tissues, activity was greater in the cytosolic fractions. In placenta, activity was evenly distributed between the cytosolic and microsomal fractions. The cytosolic fractions of each tissue contained predominantly post-proline endopeptidase activity, whereas the microsomes contained predominantly aminopeptidase activity. There was a slight trend to decreasing oxytocinase activity with advancing gestation in both subcellular fractions, but this was statistically significant only in the microsomal fraction. The maximal decline in activity was only 25-50%. Tamoxifen treatment had no effect on oxytocinase activity. We conclude that rat uterine and placental tissues contain post-proline endopeptidase and aminopeptidase activities that metabolize OT. It is doubtful that changes in these activities are major factors in regulating the increase in OT concentrations measured in rat intrauterine tissues at the time of parturition.     

Extraordinary features in the Chlamydomonas reinhardtii chloroplast genome: (1). rps2 as part of a large open reading frame; (2). A C. reinhardtii specific repeat sequence

PURPOSE: To evaluate the clinical efficacy of local vaginal lidocaine application for pain relief during high-dose-rate (HDR) intracavitary brachytherapy for patients with cervical cancer, and to investigate sequential changes in serum levels of lidocaine during the procedures. METHODS AND MATERIALS: This prospective study was designed to examine the analgesic effect, physical response, and side effects of local anesthesia during HDR intracavitary brachytherapy. Forty patients were enrolled. All patients received 10-15 MV X-rays to the pelvis with a total dose of 45-59.4 Gy 5-6 weeks before undergoing HDR intracavitary brachytherapy. All patients underwent first intracavitary brachytherapy under general anesthesia. These patients were randomly allocated to receive one of two different treatment protocols as follows: (1) treatment session - control session - treatment session - control session; or (2) control session - treatment session- control session - treatment session. In the treatment sessions, topical anesthesia was administered using 4 ml of 10% lidocaine solution sprayed liberally on the cervix and vagina during intracavitary brachytherapy. In the control sessions, a placebo was administered in the same manner during brachytherapy. The Hensche's applicators for brachytherapy were inserted into the cervix and vagina 5 min after lidocaine application. The visual analogue scale (VAS) was used to assess pain and discomfort during brachytherapy. Blood pressure and heart rates were measured to evaluate the physiological response. Another prospective study was then performed to investigate the sequential changes of serum lidocaine levels during the anesthetic procedure. Eleven additional patients with similar disease state and demographic characteristics were enrolled and blood samples were obtained before, and 5, 15, 30, and 45 min after the initiation of lidocaine application. RESULTS: The mean VAS values recorded during the treatment sessions and control sessions were 49.9 +/- 24.1 versus 60.1 +/- 24.8, respectively. The value of VAS in the treatment session was significantly lower than that of the control session (p < 0.001). No statistically significant differences were found in the changes of blood pressure and heart rate and in the incidence of side effects during these two types of sessions (p > 0.05). In the drug-level study, serum levels of lidocaine reached a peak 5 min after the initiation of local anesthesia. The mean peak concentrations (Cmax) of lidocaine were 0.50 +/- 0.45 microg/ml. CONCLUSION: Local vaginal anesthesia with 10% lidocaine solution can significantly decrease the degree of painful sensation during HDR intracavitary brachytherapy, and is safe to administer for the procedure for cervical cancer.     

Dose-volume histogram analysis of high dose rate intracavitary brachytherapy for uterine cervix cancer

PURPOSE: We retrospectively analyzed the relationship between dose distribution and local control using a dose-volume histogram (DVH) in patients with cancer of the uterine cervix treated by definitive radiotherapy including intracavitary brachytherapy. METHODS AND MATERIALS: Twenty-five patients with squamous cell carcinoma of the uterine cervix who underwent definitive radiotherapy between August 1987 and April 1994 were selected for the present study. They included 15 patients with local control and 10 patients with local recurrence. In principle, these patients were treated with 50 Gy of external beam pelvic radiotherapy and a point A dose of 24 Gy, in four fractions, of intracavitary brachytherapy. The DVHs of tumor volumes were calculated by superimposing three-dimensional (3D) dose distributions on computed tomography (CT) images taken before brachytherapy. RESULTS: Differential DVHs revealed a tendency for the portion of the total tumor volume to which the delivered dose was low to be larger in patients with local recurrence. The tumor volumes and the absolute dose volumes of which the absorbed dose was less than 24 Gy [DV (< 24 Gy)] were significantly larger in patients with local recurrence than those in local control patients (p = 0.02 and 0.03, respectively). The percent DV (<24 Gy) was not significantly different in the two groups. In patients with larger tumor volume, the absolute DV (<24 Gy) was also larger and a strong linear correlation was noted between them. CONCLUSIONS: The analysis of dose distribution of brachytherapy using DVH was useful to evaluate the quality of dose distribution quantitatively. The absolute dose volume was considered more important than the percent dose volume for evaluation of the clinical outcome. Our study suggested that unfavorable dose distribution for the tumor volume in brachytherapy was one of the reasons of poor local control in patients with large tumor volume.     

Messenger RNA synthesis, transport, and storage in silkmoth ovarian follicles

The effect on liver microsomal enzyme activity of three steroid contraceptive drug (SCD) combinations was compared in rats, mice and guinea-pigs. Lynestrenol plus mestranol, norethisterone plus mestranol and norethynodrel plus mestranol were given orally for 4 consecutive days (acute treatment) or 30 days (chronic treatment) at various doses eliciting an experimentally controlled antifertility activity which varied in its extent. In rats and mice all the combined treatments (with the exception of norethynodrel plus mestranol in mice) were active as inducers of liver microsomal enzymes. This induction seems to be mediated mainly by the progestogenic compounds. Oestrogens showed a very poor effect bordering on significance only in a few cases. No effect on liver microsomal protein or cytochrome P 450 concentration was obtained after treatment with doses capable of increasing the microsomal enzyme activity. The activity of the liver microsomal enzymes did not appear to be reduced immediately (2 h) after the last administration of the SCD given during 4 or 30 days. Contraceptive treatments at doses capable of eliciting complete antifertility activity were inactive on liver microsomal enzyme activity in guinea-pigs.     

Salvage therapy of advanced squamous cell carcinoma of the mouth cavity and oropharynx. Results of interstitial high-dose-rate brachytherapy combined with ablative tumor surgery

PURPOSE: The clinical effect of high-dose-rate (HDR) interstitial brachytherapy combined with tumor resection was investigated in this retrospective study on patients with recurrent oral and oropharyngeal squamous cell carcinoma. PATIENTS AND METHODS: Oral and oropharyngeal squamous cell carcinoma in 38 patients were treated over a period of 7 years (1988-1994) by HDR interstitial brachytherapy using Gammamed 12i equipment. Pretreatment of patients in terms of irradiation and surgery differed (33 irradiated with a total dose between 60.0 and 75.6 Gy, including 8 patients with additional surgery; 1 patient with surgery alone, and 4 patients without any pretreatment). Indications for interstitial brachytherapy differed according to individual responses to treatment and medical histories. RESULTS: Interstitial brachytherapy was successful in the majority of patients, i.e. complete remission: 12, partial remission: 19, no change: 2, progression: 5. Local control and overall survival including patients with surgical treatment was 59% and 81% at 6 months and 47% and 49% after 12 months, respectively. CONCLUSION: Interstitial HDR brachytherapy with Iridium 192 is recommended in patients with local recurrences or second primary carcinomas after previous external radiotherapy in the head and neck region. Combination of interstitial brachytherapy and surgery is preferable for these patients.     

A pilot study on concurrent platinum chemotherapy and intracavitary brachytherapy for locally advanced cancer of the uterine cervix

This study aims to evaluate the feasibility, toxicity and efficacy of concurrent chemotherapy with platinum compounds and brachytherapy, for locally advanced carcinoma of the cervix (Stages IIA/B, IIIA). The hypothesis was that synchronous chemo-brachytherapy may be sufficient to cause down-staging of the tumour, to render it operable, and hopefully improve the prognosis. 36 women with locally advanced cervical cancer were treated with concomitant brachytherapy and chemotherapy before surgery and/or definitive external radiotherapy. All patients received two caesium-137 Selectron MDR applications, 1 week apart. The dose calculated to point A for each implant was 20-25 Gy. Chemotherapy consisting of continuous cisplatin infusion (50 mg m2) and of carboplatin (300 mg m-2) was given simultaneously with intracavitary irradiation during the first and second application, respectively. The combined therapy was followed when feasible by radical hysterectomy, pelvic lymphadenectomy and pelvic radiotherapy. Patients deemed ineligible for surgery because of poor response were given full dose external radiotherapy. 31/36 patients were treated by Wertheim hysterectomy of whom 10 had negative lymph nodes and resection margins. Definitive external radiotherapy was given in the remaining five patients. Overall, 83% were disease free at 2.8 years mean follow-up. The most frequent acute side-effects of chemobrachytherapy were nausea and vomiting. No renal toxicity was observed. Thrombocytopenia was seen in five patients and was responsible for delayed surgery in four patients. Concerning late effects, two patients developed grade 2 intestinal sequelae, two mild frequency and two vaginal stenosis. One rectovaginal and one vesicovaginal fistula developed in two patients; and a third patient had a fistula associated with tumour recurrence. Concurrent brachytherapy and chemotherapy with platinum compounds is well tolerated and effective in reducing tumour bulk before definitive local treatment (surgery or external radiotherapy), in patients with locally advanced carcinoma of the uterine cervix.     

Anthropometric measurements and vertebral deformities. European Vertebral Osteoporosis Study (EVOS) Group

BACKGROUND: Plasma levels of B-type natriuretic peptide (BNP) are markedly increased in patients with heart failure and acute myocardial infarction. The changes in plasma BNP levels in the treatment of acute myocardial infarction with angiotensin-converting enzyme inhibitors have not been examined well. This study was designed to examine the effects of early angiotensin-converting enzyme inhibitor therapy on plasma BNP levels in patients with acute myocardial infarction. METHODS AND RESULTS: We measured the plasma levels of B-type natriuretic peptide over the time course for 2 weeks in 30 patients with acute myocardial infarction in whom either imidapril (n = 15) or placebo (n = 15) was given at random immediately after admission. Plasma BNP levels increased and reached a peak of 192 +/- 28 pg/ML 16 hours after administration; thereafter, the levels decreased and then again increased, forming the second peak of 217 +/- 38 pg/ML on the fifth day (biphasic pattern). On the other hand, plasma BNP levels increased and reached a peak level of 190 +/- 22 pg/ML 16 hours after admission and then decreased from 2 days after admission until the second week in the imidapril group (monophasic pattern). Left ventricular ejection fraction measured in the second week was significantly higher in the imidapril group than in the control group (62.2 +/- 1.1% vs 51.2 +/- 3.6%, P < .01). CONCLUSION: It is concluded that plasma BNP levels followed a monophasic pattern after imidapril treatment, whereas a biphasic pattern was followed after placebo, and that plasma BNP levels constitute a marker of ventricular dysfunction in the treatment of acute myocardial infarction with angiotensin-converting enzyme inhibitors.     

Correction of postoperative metabolic alkalosis and renal failure by hemodialysis

Arylamidase activity in human endometrium tissue, uterine fluid, and serum in uterine dysfunction induced by a copper IUD, steroidal contraception, and lactational amenorrhea was investigated. Arylamidase activity in cell-free preparation of endometrium increased steadily from the early proliferative phase attaining the maximum level at the secretory phase. The activity in the uterine fluid and serum showed similar trends. In uterine dysfunction, the activity decreased in different conditions. The distribution of the enzyme activity in the particular and soluble fractions was within a close range (1.4 to 1.7), indicating the absence of transfer of enzyme from particulate to the soluble fraction. The administration (in vitro) of 10 -4 M estrogen and progesterone caused an increase in the activity. Substrate affinity values of the enzymes in both fractions remained unaffected while the catalytic phase values were altered indicating a qualitative difference in the 2 enzymes.     

Contribution of peroxidation products to oxidative inactivation of rat liver microsomal glucose-6-phosphatase

Exposure of rat liver microsomes to ascorbic acid/Fe(2+) caused decreases in the membrane-bound glucose-6-phosphate (G-6-Pase) activity and the protein thiols after a short lag period (4 min). Under the same conditions, the production of thiobarbituric acid-reactive substances and fluorescent products was also initiated from 4 min after the start of the treatment, although conjugated diene was formed immediately on incubation of the microsomes with ascorbic acid/Fe(2+). After centrifugation of the treated microsomes, the fluorescent products and the enzyme activity remained in the membrane fraction. The results of kinetic studies of the enzyme activity indicated that ascorbic acid/Fe(2+)-induced inhibition of the enzyme activity is mainly due to an increased Km value for the substrate. A decreased activity of the microsomal G-6-Pase was also observed when the microsomes were incubated with aldehydes such as malondialdehyde, n-heptaldehyde, acetaldehyde, and trans-2-nonenal. However, loss of protein thiols was detected only upon treatment of the microsomes with trans-2-nonenal. Glucose-6-phosphate (G-6-P)effectively prevented ascorbic acid/Fe(2+)- or trans-2-nonenal-induced inhibition of the enzyme activity, but the substrate failed to protect the protein thiols in both systems. The results of fluorescence anisotropy measurements of diphenylhexatriene-labeled microsomes suggested that changes in the lipid dynamics are not directly related to peroxidation- mediated inhibition of the enzyme activity. Based on these results, a possible reason for the inhibition of the microsomal G-6-Pase activity associated with ascorbic acid/Fe(2+) treatment is discussed.     

Mental symptoms in Parkinson''s disease during chronic treatment with levodopa

The influence of epidural block with bupivacaine (Marcaine-adrenalin) on fetal heart rate, uterine activity, and the frequency and intensity of contractions was studied in twenty-five nulliparae at term. Uterine activity was found to decrease during the first 30 minutes following epidural block. In the time interval 30 to 40 minutes after epidural block uterine activity increased again and attained the same level as during the last 10 minutes before analgesia. The frequency of uterine contractions did not decrease after the block. The lower levels of uterine contractility were due only to a lower amplitude of the contractions. The regularizing effect of epidural analgesia on incoordinate uterine action was noted. The recording of fetal heart rate in the time interval studied revealed no pathological findings. Mode of delivery, mean labour duration and Apgar scores after epidural block were comparable with earlier studies of a larger patient population. This study suggest that epidural analgesia does not induce any important changes in fetal heart rate but temporarily decreases uterine activity.     

Telomerase activity in ovarian tumors

BACKGROUND: Shortening of telomeres occurs with each cell division and eventually results in cell death. The activity of telomerase, an enzyme that catalyzes telomere elongation, has been detected in germ cell lines and cancer cells, and has been detected in immortal cell lines but not in normal somatic cells. The relationship between telomerase expression and ovarian carcinogenesis was investigated. METHODS: Ovarian tissue was obtained from 41 women with ovarian tumors (10 benign, 6 borderline-malignant, and 25 malignant tumors) and 6 with uterine disease (2 with uterine myoma and 4 with uterine carcinoma). These specimens were analyzed for telomerase activity and telomere length by the telomeric repeat amplification protocol and Southern blot hybridization, respectively. RESULTS: Telomerase activity was detected in 23 of 25 malignant ovarian tumors (92%), in 1 of 6 borderline-malignant tumors (16.7%), and in 2 of 10 benign tumors (20%) (both of which were germ cell tumors). Weak telomerase activity was present in the cortex of normal ovaries from premenopausal women, and appeared to be attributable to follicles. Telomerase activity in malignant and poorly differentiated tumors tended to be higher than that in other tumors. Terminal restriction fragment length ranged between 8 and 13 kilobase pairs (kbp) for normal ovaries, and was <8 kbp in 1 of 6 malignant Stage I tumors (16.7%), 1 of 2 Stage II tumors (50%), and 9 of 17 Stage III tumors (52.9%). CONCLUSIONS: Telomerase activity may be a useful marker for the diagnosis of ovarian tumors.     

Cystoscopic staging of carcinoma uterine cervix, revisited

Of the 378 cases of stage 3 carcinoma uterine cervix, only 10 showed vesical invasion, while 19 of 24 cases of stage 4 disease had vesical invasion. Results of this procedure did not alter the management of the disease in any of these cases. From the whole series it was concluded that cysto-urethroscopy is an unnecessary, cost ineffective, invasive procedure which has no role in either diagnosis or in planning the definitive treatment of carcinoma uterine cervix.     

United States Thrombotic Thrombocytopenic Purpura Apheresis Study Group (US TTP ASG): multicenter survey and retrospective analysis of current efficacy of therapeutic plasma exchange

PURPOSE: Clinical experiences in interstitial 192-iridium HDR brachytherapy for the treatment of unresectable pancreatic carcinoma are presented. Brachytherapy has been used as boost irradiation in a multimodality treatment concept together with external radiotherapy and simultaneous chemotherapy. Practicability during clinical routine, tolerability and toxicity of treatment are investigated. PATIENTS AND METHODS: Nineteen patients (9 female, 10 male, median age 67 years) with unresectable carcinoma of the pancreas have been treated with interstitial brachytherapy. Distribution according to UICC stages showed 4, 10 and 5 patients in stage II to IV respectively. In all cases afterloading technique with 192-iridium in HDR-modus was used. A total dose of 10 to 34 Gy to the reference isodose was delivered (single dose 1.88 to 5 Gy, median 2.5 Gy). Brachytherapy was followed by external radiotherapy, delivering an additional dose of 40 to 58 Gy. Nine patients received simultaneous chemotherapy (5-fluorouracil, leucovorin). Treatment planning was performed based on CT scans, allowing spatial correlation of isodose curves to the patient's anatomy. RESULTS: Median survival time was 6 months. A trend of lower survival rates with advanced stage of disease (median survival stage IV 4 months, stage II and III 6.5 months) was seen. Local control rate was 70%. Brachytherapy treatment was well tolerated, severe acute side effects were not observed. One patient developed pancreatic fistulae 4 months and 1 patient a gastric ulcer 7 months after treatment. Pain release was achieved in all patients. CONCLUSIONS: 192-iridium HDR-brachytherapy is an effective tool in the treatment of unresectable pancreatic carcinoma with a high rate of local control and a low rate of side effects and is comparable IORT or seed implantation.     

Strengthening the interdisciplinary education of nurses in violence prevention, detection, and intervention

The diagnostic significance of amylasuria in the early period of an acute biliary pancreatitis (ABP) course was estimated in 70 patients. High sensitivity of the test during 3 days of the disease course was ascertained as well as a lack of specificity of the criterion concerning differential diagnosis with an acute cholecystitis. The interrelationship between the enzyme activity and lethality was not revealed. It is necessary to take into account the peculiarities of the amylasuria diagnostic-prognostical significance while substantiation of diagnostic program and the treatment tactics for ABP.     

Quantitative changes of glyco- and mucoproteins in the serum of patients with carcinoma of the uterus during treatment

The mutations of serum glycoproteid and mucoproteid levels were examined in 40 patients with uterine cancer before, during and 4 years after treatment. In all the patients having become symptom-free the glycoproteid and mucoproteid concentration, that had shown an initial increase before, returned to normal in the course of successful treatment. There could be found no connection between the tumor extension and the otherwise increased serum values in carcinoma of cervix and uterus of stage I. and II.     

Ten-year disease free survival after transperineal sonography-guided iodine-125 brachytherapy with or without 45-gray external beam irradiation in the treatment of patients with clinically localized, low to high Gleason grade prostate carcinoma

BACKGROUND: The authors report observed 10-year brachytherapy results in the treatment of 152 consecutive patients with clinically organ-confined prostate carcinoma. METHODS: One hundred and fifty-two consecutive patients with T1-T3, low to high Gleason grade, prostate carcinoma were treated between January 1987 and June 1988 at Northwest Hospital in Seattle, Washington. Their median age was 70 years (range, 53-92 years). Of these 152 patients, 98 (64%) received an iodine-125 implant alone (Group 1), and the remaining 54 patients (36%), who were judged to have a higher risk of extraprostatic extension, also were treated with 45 gray (Gy) of external beam irradiation to the pelvis (Group 2). No patient underwent lymph node sampling, and none received androgen ablation therapy. Multivariate regression and the Mann-Whitney rank sum test were used for statistical analysis. Preoperative patient data with associated success or failure outcomes at 10 years after treatment were used for training and validating a back-propagation neural network prediction program. RESULTS: The average preoperative prostate specific antigen (PSA) value, clinical stage, and Gleason grade were 11.0 ng/mL, T2, and 5, respectively. The median posttreatment follow-up was 119 months (range, 3-134 months). Overall survival 10 years after treatment was 65%. At last follow-up only 3 of the 152 patients (2%) had died of prostate carcinoma. Ninety-seven patients (64%) remained clinically and biochemically free of disease at 10 years of follow-up and had an average PSA value of 0.18 ng/mL (range, 0.01-0.5 ng/mL). In these patients a period of 42 months was required to reach the average PSA (0.5 ng/mL). The median to last PSA follow-up was 95 months (range, 3-134 months). Postoperative needle biopsies were negative in 56% of patients, positive in 15% of patients, and not available in 29% of patients. Only 6% of patients developed bone metastasis. At 10 years there was no statistically significant difference in treatment outcome between patients who received iodine-125 alone, and those who received iodine-125 with 45-Gy external beam irradiation (P = 0.08). Nevertheless, in these two groups preoperative PSA, stage, and Gleason grade were significantly different (P < 0.01). In the artificial neural network analysis, pretreatment serum PSA was the most accurate predictor of disease-free survival. CONCLUSIONS: Percutaneous prostate brachytherapy is a valid and efficient option for treating patients with clinically organ-confined, low to high Gleason grade, prostate carcinoma. Observed 10-year follow-up documents serum PSA levels superior to those reported in several published external beam irradiation series, and comparable to those published in a number of published radical prostatectomy series.     

Recombinant phosphoglycerate kinase from the hyperthermophilic bacterium Thermotoga maritima: catalytic, spectral and thermodynamic properties

BACKGROUND: Results from localized prostate cancer series using seed implants have been most encouraging. However, with current techniques, inadequate dosimetry sometimes occurs. Remote afterloading high dose rate 192Iridium brachytherapy (HDR-Ir192) theoretically remedies some potential inadequacies of seed implantation by performing the dosimetry after the needles are in place. This study was undertaken to determine the feasibility of incorporating multifractionated HDR-Ir192 in the brachytherapy management of prostate carcinoma. METHODS: From October 1989 to August 1995, 104 patients were treated with a combination of multifractionated HDR-Ir192 and external beam. Patients ranged in age from 48-78 years, with a mean of 68.6 years. By TNM clinical stage, there were 1 T1b, 31 T1c, 28 T2a, 24 T2b, 9 T2c, 8 T3a, and 3 T3c lesions. For the group, the mean initial pretreatment PSA was 12.9 ng/ml (median 8.1), with 90% of the patients having had a pretreatment PSA greater than a normal value of 4.0 ng/ml. Patients with prostate volumes up to 105 cc were implanted. Treatment was initiated with perineal needle placement using ultrasound guidance. A postoperative CT scan was obtained to provide the basis for treatment planning. Four HDR-Ir192 treatments were given over a 40-h period, with a minimal peripheral dose (MPD) ranging from 3.00 to 4.00 Gy per fraction over the course of this study. Two weeks later, external beam radiation was added using 28 fractions of 1.80 Gy daily, to a dose of 50.40 Gy. Results: Follow-up ranged from 10 to 89 months, with a mean of 46 months and median of 45 months. At various follow-up points, the patient numbers at risk were: 1 year, 101; 3 years, 69; 5 years, 28. The technique proved to be uniformly applicable to a wide range of prostate volumes and was very well tolerated by patients. Nearly all significant late in-field treatment complications were genitourinary in nature. Of the patients, 6.7% developed urethral strictures that were readily manageable. Changes in technique implemented in 1993 appear to have significantly lessened the incidence of this complication. Two patients developed significant uropathy within the first treatment year, but both resolved; 1 of these 2 patients had a prior TURP. Other bladder or rectal complications have been minimal. Using PSA progression as a marker of tumor response, approximately 84% of patients whose initial PSA was less than 20 ng/ml were free of progression at 5 years by actuarial analysis. CONCLUSIONS: We found the use of transperineal ultrasonography, postimplant CT-based dosimetry, coupled with adjustable dose delivery inherent to remote afterloading technology, to give unparalleled control in performing this complex brachytherapy task. Thus, it may be advantageous in certain clinical situations where the resultant MPD is needed to reliably cover the target volume, such as in patients with carcinomas at base locales, when the possibility of moderate to extensive intraprostatic tumor exists, and in patients with large glands. Early PSA data suggest that it may be effective as a definitive treatment with rates of adverse late tissue effects that are acceptable using current technique and doses described herein. Longer follow-up is needed to ascertain its position among the various treatment regimens for prostate carcinoma.