Phase II prospective study of the use of conformal high-dose-rate brachytherapy as monotherapy for the treatment of favorable stage prostate cancer: a feasibility report.

PURPOSE: To evaluate the technical feasibility and tolerance of image-guided transperineal conformal high-dose-rate (C-HDR) brachytherapy as the sole treatment modality for favorable, localized cancer of the prostate, and to analyze possible intrafraction and interfraction volume changes in the prostate gland which may affect dosimetric quality. METHODS AND MATERIALS: Patients were eligible for this prospective Phase II trial if they had biopsy proven adenocarcinoma of the prostate with favorable prognostic factors (Gleason score < or =7, PSA < or =10 ng/ml and Stage < or =T2a). The technique consisted of a transperineal implant procedure using a template with transrectal ultrasound (TRUS) guidance. An interactive on-line real-time planning system was utilized with geometric optimization. This allowed dosimetry to be generated and modified as required intraoperatively. Prescription was to the minimum dose point in the implanted volume, assuring conformal coverage of the prostate at its widest dimension with no margin. Total dose was 3800 cGy in 4 fractions of 950 cGy each, delivered twice a day over 2 days. The dose to any segment of rectum and urethra was limited to < or =75% and < or =125% of the prescription dose, respectively. Before each fraction, needle positions were verified under fluoroscopy and adjusted as required. For the last 10 patients, the adjustments required were measured in a prospective fashion in representative extrema of the gland. TRUS images were recorded for all patients before any needle manipulation, again just before delivering the first fraction and immediately after the last fraction. This typically meant approximately 36 h to pass between the first and last measurements. Implant quality was assessed via dose-volume histograms (DVH). RESULTS: Between 3/99 and 6/00, 41 patients received C-HDR interstitial brachytherapy as their only treatment for prostate cancer at our institution. Median age was 64 years (range 51-79). Stage distribution was 27 T1c patients and 14 T2a patients. Three patients had Gleason score (GS) of 5; 34 had GS of 6; 4 patients had GS of 7. Median pretreatment PSA was 4.7 ng/ml (range 0.8-13.3). All patients tolerated the treatment well with minimal discomfort. For 23 patients, data on volume changes in the gland during the implant were tabulated. They demonstrated a mean prostate volume of 30.7 cc before any manipulation with needles, 37.0 cc at the end of fraction 1, and 38.2 cc at the end of fraction 4. In addition, for those 10 patients prospectively evaluated for required adjustments, the overall mean adjustment between fraction 1 and fraction 2 was 2.0 cm, between fraction 2 and 3 was 0.4 cm, and between fractions 3 and 4 was 0.4 cm. For 10 consecutive patients, the average prescriptions dose -D90 for fractions 1 and 4 were 104% and 100%, respectively. The corresponding average urethral D10 for fractions 1 and 4 were 122% and 132%. CONCLUSION: Our protocol using C-HDR interstitial brachytherapy as monotherapy for early cancer of the prostate was feasible and well tolerated by 41 patients treated. Changes in interfraction prostate volume do not appear to be significant enough to warrant modification of dosimetry for each fraction. Both excellent dose coverage of the prostate gland and low urethral dose are achieved as measured by DVH. However, paramount attention should be given to needle displacement before each fraction. Needle movement is most significant between fractions 1 and 2. Acute toxicity (RTOG) has been modest. Late toxicity and tumor control rates will be reported as longer follow-up allows.

Effects of orexins on the hypothalamic-pituitary-adrenal system.

The effects of the recently identified neuropeptides orexin-A and orexin-B on the hypothalamic-pituitary-adrenal (HPA) system were investigated. An in vivo system was used to assess the central effects of both orexin-A and orexin-B. Different doses of the orexins (2.8-560 pmol) were administered intracerebroventricularly (i.c.v.) to adult male rats, and plasma corticosterone was used as an index of the degree of the activation of the HPA system. Both peptides exhibited a clear dose-response action, although orexin-B proved to be less effective than orexin-A. Pretreatment with the corticotropin-releasing hormone (CRH) antagonist alpha-helical CRH9-41 completely prevented the action of the orexins. Orexin-A, orexin-B or adrenocorticotropic hormone (ACTH) was further administered intraperitoneally (i.p.). While ACTH evoked a significant adrenal response, the orexins did not influence the basal secretion. Adrenal slices, oxygenized and perifused with Krebs' solution, were also treated with orexin-A, orexin-B or ACTH. Both orexins failed to modify the release of corticosterone, but ACTH induced a marked adrenal response. This study suggests that these appetite-regulating peptides might activate the HPA system at a central level but neither orexin-A nor orexin-B appears to modulate directly the adrenal corticosterone release.

Isatin (Indole-2, 3-dione) inhibits natriuretic peptide-induced hyperthermia in rats.

The effects of an endogenous indole, isatin (indole-2, 3-dione), on the hyperthermia induced by atrial natriuretic peptide (ANP-28), brain natriuretic peptide (BNP-32), and C-type natriuretic peptide (CNP-22) were investigated in rats. Intracerebroventricular administration of each peptide in a dose of 1 microg caused elevations in colon temperature 30 and 60 min after injection. An intraperitoneal (i.p.) injection of isatin (50 mg/kg) abolished the natriuretic peptide-induced hyperthermia. These data reinforce the possible involvement of natriuretic peptides in thermoregulatory processes in the central nervous system, and suggest that isatin might counteract their hyperthermic effect in vivo.

Pituitary adenylate cyclase-activating polypeptide induces hyperthermia in the rat.

The effects of centrally administered pituitary adenylate cyclase-activating polypeptide (PACAP-38) on body temperature were investigated in rats. Intracerebroventricular (i.c.v.) administration of PACAP-38 in doses of 500 and 1000 ng induced a dose-related elevation in colon temperature 2, 3, 4, 5 and 6 h after injection. The i.c.v. pretreatment of the animals with different dilutions of PACAP-38 antiserum prevented the development of hyperthermia in PACAP-38-treated animals, whereas PACAP-38 antiserum alone did not modify the colon temperature. An intramuscular injection of noraminophenazone (a cyclooxygenase inhibitor) abolished the PACAP-38-induced hyperthermia. Our data indicate that PACAP may induce hyperthermia via the central nervous system, and this hyperthermic effect may be mediated via a cyclooxygenase-involved pathway.

Hyperthermic effect of centrally administered natriuretic peptides in the rat.

The effects of atrial natriuretic peptide (ANP-28), brain natriuretic peptide (BNP-32) and C-type natriuretic peptide (CNP-22) on body temperature were investigated in rats. Intracerebroventricular administration of each peptide in doses of 400 or 1000 ng caused a dose-related elevation in colon temperature 30 and 60 min after injection. A 40 ng dose of ANP-28 was also hyperthermic at 60 min. An intramuscular (i.m.) injection of noraminophenazone (a cyclooxygenase inhibitor) abolished the natriuretic peptide-induced hyperthermia. The results show that natriuretic peptides may participate in thermoregulatory processes in the central nervous system, and that their hyperthermic effect may be mediated via a cyclooxygenase-involved pathway.

Further evidence that nitric oxide modifies acute and chronic morphine actions in mice.

The effects of the nitric oxide (NO) synthase inhibitor, N(omega)-nitro-L-arginine (L-NNA, 2.5-10 microg i.c.v.), and the NO synthesis precursor, L-arginine (L-Arg, 2.5-10 microg i.c.v.), on morphine-induced analgesia, and on morphine-induced tolerance and dependence were examined in mice. Administration of L-NNA diminished the morphine-induced analgesia. L-Arg pretreatment increased the analgesic effect of morphine. Repeated pretreatment (three times, at 24-h intervals) with L-NNA diminished both acute and chronic tolerance to morphine, whereas both the acute and the chronic morphine-induced tolerance increased after the repeated (three times, at 24-h intervals) administration of L-Arg. Neither L-NNA nor L-Arg affected the signs of morphine dependence, as assessed by naloxone (1 mg/kg, s.c.)-precipitated withdrawal. Our data suggest that increased NO synthesis potentiates morphine analgesia and enhances the development of morphine tolerance in mice.

[Nosocomial ornithosis]. / Nosocomialis ornithosis.

Ornithosis is an occupational hazard to workers in the poultry industry, zoonosis. Own sporadic unusual case is appearing under the hospital circumstances as a nosocomial atypical pneumonia.

Assessment of cartilage volume in the femorotibial joint with magnetic resonance imaging and 3D computer reconstruction.

OBJECTIVE: Our goal was the development of an accurate and objective technique to depict and quantitate articular cartilage using magnetic resonance imaging (MRI) and 3D data processing. METHODS: A method of 3D image analysis has been developed that provides a noninvasive technique of measuring cartilage volume from standard diagnostic MR images. RESULTS: Using a computer workstation, cartilage from Fast Field Echo (FFE) MR images was reconstructed into 3 dimensions (3D). The accuracy and reproducibility of both thickness and volume measurements obtained from the existing computer software was tested using calibration test objects. We describe the sources of error we encountered when attempting to quantitate cartilage using the existing computer software, the methods developed to reduce these errors, and a preliminary cartilage volume study using healthy human volunteers. CONCLUSION: We have identified errors involved in attempting cartilage volume estimations using the existing 3D computer software and have developed a data processing technique that minimizes these errors. With these objective data processing techniques we have improved the reproducibility of the technique to +/- 10-15% error. This modified technique provides a promising new method for viewing and quantifying cartilage volume from standard diagnostic MR images.

Cervical and vaginal microflora of women under cancer screening.

Gynaecological cancer screening was supplemented with examination of the vaginal microflora and pH in women suffering from vaginal discharge and/or colpitis. In alkaline samples Escherichia coli, Staphylococcus aureus and Candida albicans and, in cervical epithelial cells, herpes simplex virus antigen were of common occurrence, while in samples with acid reaction Trichomonas and, in cervical cells mainly from pregnant women, adenovirus antigen were often detected. Since vaginal pH may be informative of the pathogenic agent(s), its estimation by a rapid, simple and painless procedure, like litmus paper reaction, is recommended.

Isolation of aerobic bacteria from the placenta.

Cultures for aerobic bacteria were prepared from 353 placentas. Specimens were taken from the chorion after removing the amnion. The specimens were immersed into Stuart transport medium. Microscopic examination of the placenta and cultures from the throat and ear of newborns were also done. The rate of positive bacterial cultures was 16%. Chorioamnionitis was found in 15%. The proportion of chorioamnionitis caused by aerobic bacteria was 44%. The rate of positive bacterial cultures from the placenta in the group of newborns with clinical signs of intrauterine infection was 63%. Bacteria can be present on the chorionic plate without any histological evidence of chorioamnionitis. Bacteriological examination of the placenta is therefore mandatory when amniotic fluid infection is suspected.