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[Correlation between re-biopsy one year after endocrine therapy and long-term prognosis in localized prostate cancer].

PURPOSE: Even in the cases of localized prostate cancer, there are a substantial number of patients who undergo endocrine therapy, and their prognosis is affected by the treatment. We evaluated the histological effect of endocrine therapy and analyzed its correlation with prognosis. METHODS AND SUBJECTS: Seventy-seven cases with localized prostate cancer who underwent maximal androgen blockade (MAB) therapy 1 year or longer were pathologically evaluated using repeat biopsy specimens from November 1994 to October 2001. The relationship between clinical parameters and histological effect in repeat biopsy specimens was examined. Biopsy was conducted mainly by the 6-site systematic method, and the histological effect was judged in accordance with the General Rules for Clinical and Pathological Study of Prostate Cancer (3rd edition). The median re-biopsy and follow-up periods were 13 months and 41 months, respectively. RESULTS: Using this criteria for the histological effects of anti-cancer treatment, the histological effect of endocrine therapy was most frequently observed in class G3b with 61.0%, and correlations with PSA nadir and initial biopsy positive number before endocrine therapy were observed. After biopsy, radical prostatectomy was performed on 9 patients (endocrine therapy was concurrently performed on 4), endocrine therapy on 67 (intermittent administration on 21), and radiation therapy on 1 (MAB was concurrently performed). Outcomes included PSA failure in 14, of whom 2 died of cancer. Three-year and 5-year PSA-failure free survival rates were 91.1% and 76.3%, respectively. Pathological disease stage in radical prostatectomy specimens was examined by dividing it into class G0-2 and class G0-3. This revealed a significant correlation between histological effect and pathological disease stage (pT2-3). PSA-failure free survival was analyzed in 67 of the 77 patients who underwent endocrine therapy. A significantly large number of PSA-failures occurred in class G0-2. Multivariate analysis revealed that the histological effect alone was the influencing factor in PSA-failure. CONCLUSION: A strong histological effect by MAB 1 year or longer after treatment was observed on localized prostate cancer. Evaluation of the histological effect by the present method was considered to be a useful predictor for organ-confined disease after radical prostatectomy and endocrine therapy for PSA-failure.

Aged↗

[In vitro antifungal activity of itraconazole, a new triazole antifungal agent, against clinical isolates from patients with systemic mycoses].

The in vitro antifungal activity of itraconazole (ITZ), a new oral triazole antifungal agent, against clinical isolates from patients with systemic mycoses were compared with those of existing systemic antifungals, viz. ketoconazole (KCZ), miconazole or amphotericin B. The studies were performed with 65 isolates of pathogenic yeasts and 13 isolates of Aspergillus spp. using the agar dilution method on casitone agar. ITZ showed the most potent antifungal activities against isolates of pathogenic yeasts including several Candida spp. (Candida parapsilosis, Candida krusei, Candida guilliermondii), Cryptococcus neoformans, Trichosporon cutaneum (MIC less than or equal to 0.08 micrograms/ml) and Aspergillus spp. including Aspergillus fumigatus (MIC less than or equal to 5 micrograms/ml). On the other hand, activities of ITZ against isolates of other Candida spp. such as Candida albicans and Candida glabrata were lower than those of KCZ and other reference drugs. Some isolates of C. albicans and C. tropicalis were not completely inhibited by ITZ even at concentrations above 10 micrograms/ml on casitone agar. However, in the micro-broth dilution method using synthetic amino acid medium, fungal as the test medium, ITZ completely inhibited the growth of all these isolates at drug concentrations of less than or equal to 0.20 micrograms/ml.

Amphotericin B↗

Aspects of fluid dynamics applied to the larger arteries.

A review is given of some of the ideas from fluid mechanics which are considered essential background for researchers in cardiovascular flows. The paper links the topics discussed at a fundamental level with real problems which, in the experience of the author, occur in research. In particular, approximate equations governing the principal phenomena, and which help with understanding, are introduced. A description is given of the equations of motion and the significance of similarity parameters is discussed: it is shown how Reynolds number and the Womersley parameter arise from dimensionless forms of the equations. Steady flow equations and approximations are commented on, including illustrations of their use. Unsteady flow phenomena are introduced and it is shown how Stokes' first and second problems illustrate key aspects of unsteady viscous diffusion and boundary layers in the circulation. Important features of pulsatile pipe flow, as analysed by both Uchida and Womersley, are discussed and linked to Stokes' two-dimensional results. Entrance effects in steady and unsteady pipe flow are compared and contrasted. Other phenomena discussed include the effects of bends in vessels, transition to turbulence and the different time-scales associated with unsteady flows. Computational methods, which are assuming increasing importance in biological fluid mechanics, also receive a brief description. Finally, comments are made on pressure and other measurements and the need for an understanding of various fluid flow phenomena when planning measurements and interpreting the resulting data.

Animals↗

Magnetic resonance imaging of reticulo-endothelial system in patients with idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP) is characterized by accelerated platelet destruction in the reticulo-endothelial system (RES). We performed magnetic resonance imaging (MRI) to estimate the degree of activated RES. MRI was performed with a Gyroscan S-15 (1.5 tesla) in 7 healthy volunteers and 22 patients with ITP. The 22 patients included 19 who were at initial diagnosis or were nonresponders to the therapy (non-DX group), and 3 who were responders. For the non-DX group, the T1 relaxation time of the spleen was initially significantly shorter than for healthy volunteers, but normalized after responding to the therapy. The initially shorter T1 values of the spleen for ITP patients correlated with a low platelet count (P < 0.05). This condition may indicate foam cells or fatty components due to platelet destruction. There was no significant relationship between the sequestration in (111)In-scan and T1 values of the liver or spleen. However, MRI is a noninvasive method, and it may be a clinically useful tool in the evaluation of RES in patients with ITP.

Adolescent↗

Segmental embolotherapy for hepatic cancer: keys to success.

Transcatheter chemoembolization using Lipiodol (Lp) mixed with chemotherapeutic agents followed by Gelfoam particle injection only to the tumor-bearing hepatic segment (segmental Lp transcatheter hepatic artery embolization) (TAE) was applied to more than 100 patients with hepatocellular carcinoma and metastatic liver cancer. For segmental Lp-TAE, knowledge of the variations of intrahepatic arterial anatomy is important. Furthermore, the catheters and guidewires, volume of Lp, kinds and dose of chemotherapy, preparation of the mixture of Lp and chemotherapy (Lp-emulsion), method of injection of Lp-emulsion and Gelfoam particles, as well as the follow-up computed tomography examination are key items to the success of the procedure and are reviewed.

Antineoplastic Agents↗

Wavelet analysis for detecting body-movement artifacts in optical topography signals.

We have developed a wavelet-based method of detecting body-movement artifacts in optical topography (OT) signals. Although OT, which is a noninvasive imaging technique for measuring hemodynamic response related to brain activation, is particularly useful for studying infants, the signals occasionally contain undesirable artifacts caused by body movements, so data corrupted by body-movement artifacts must be eliminated to obtain reliable results. For this purpose, we applied a wavelet transform to automatically detect body-movement artifacts in OT signals. We measured OT signals from nine healthy infants in response to speech stimuli. After the continuous signals had been divided into blocks (a block is a time series of OT signal in a 30-s period including a 10-s stimulation period), they were classified into two groups (movement blocks and non-movement blocks) according to whether the participants moved or not by video judgment. Using those data, we developed a wavelet-based algorithm for detecting body-movement artifacts at a high discrimination rate being consistent with the actual body-movement state. The wavelet method has two parameters (scale and threshold), and a Monte Carlo analysis gave the mean optimal parameters as 9+/-1.9 (mean+/-standard deviation) for the scale and as 42.7+/-1.9 for the threshold. Our wavelet method with the mean optimal parameters (scale=9, threshold=43) achieved a higher discrimination rate (mean+/-standard deviation: 86.3+/-8.8%) for actual body movement than a previous method (mean+/-standard deviation: 80.6+/-8.7%) among different participants (paired t test: t(8)=2.92, p<0.05). These results demonstrate that our wavelet method is useful in practice for eliminating blocks containing body-movement artifacts in OT signals. It will contribute to obtaining reliable results from OT studies of infants.

Artifacts↗

Development of a kinetic assay for band 5b tartrate-resistant acid phosphatase activity in serum.

BACKGROUND: Band 5 tartrate-resistant acid phosphatase (TrACP; EC 3. 1.3.2) consists of two isoenzymes, bands 5a and 5b, of which band 5b TrACP is considered to be derived from bone. However, no kinetic method for the specific measurement of band 5b TrACP in serum is available. Our aim was to develop a kinetic assay method for the specific measurement of band 5b TrACP in serum. METHODS: Band 5b TrACP was measured kinetically in serum as tartrate-resistant fluoride-sensitive heparin-resistant ACP with 2, 6-dichloro-4-acetylphenyl phosphate as substrate at pH 6.6. RESULTS: Heparin inhibited band 5a TrACP but had no effect on band 5b TrACP in serum or in bone extract. The presence of EDTA or ascorbic acid had no effect, but dithiothreitol inhibited enzyme activity. The within-run (n = 20) and between-run (n = 20) CVs of band 5b TrACP activity were 3.3-5.8% and 5.0-7.3%, respectively. The mean +/- SD values of band 5b TrACP activity in males (n = 25) and females (n = 57) 20-29 years of age by this method were 8.0 +/- 2.2 U/L and 6.4 +/- 1.8 U/L, respectively. The band 5b TrACP value was significantly higher in females >50 years of age compared with the younger subjects (20-29 years). The highest band 5b TrACP values were among children younger than 15 years. CONCLUSIONS: This kinetic assay is a simple and specific method for the measurement of band 5b TrACP in serum samples and is useful in the evaluation of bone turnover activity.

Acid Phosphatase↗

[Effects of Nd:YAG laser irradiation on ventricular myocardium in dogs using an artificial sapphire tip contact laser catheter].

To apply Nd:YAG laser irradiation through a new sapphire tip contact laser method to catheter ablation in treatment of tachy-arrhythmias, effects of laser irradiation on ventricular myocardium were investigated in 10 mongrel dogs. Nd:YAG lase (1064nm) discharges were delivered to different sites on the endomyocardium at power of 5, 10, 15, 20 or 25w with duration of 3, 5, or 10 seconds (sec.) respectively in closed beating hearts. Histopathologically, the lesion irradiated was clearly demarcated from the normal myocardium by the construction band necrosis zone. The depth of injured myocardium was less than 2mm with 3 sec. irradiations, with 5 sec. from 1 mm to 4 mm in proportion to power increase, with 10 sec. from 3mm to 8 mm in proportion to the power from 5w to 15w and could not be measured in cases of more than 20w irradiations. Although with every irradiation duration, the depth of injury increased in proportion to the power increase. With the same total energy, a longer time of irradiation produced deeper injury than a shorter time. This method makes it easier to keep the laser positioned to target than bare laser, and is suitable for use in catheter ablation.

Animals↗

[Demonstration of PIVKA-II and AFP production by gastric cancer by indirect immunoenzymatic staining of paraffin sections].

The patient had elevated plasma PIVKA-II and serum AFP levels. However, no tumor was detected with an ultrasonography, angiography, abdominal computed tomography (CT), and magnetic resonance imaging (MR). Gastric endoscopic examination disclosed gastric cancer and then subtotal gastrectomy was done. Shortly after the surgery, both plasma PIVKA-II and serum AFP levels returned to each normal level. The extirpated tumor revealed histologically immature and mature cancer cells. It was pathologically diagnosed as IIc early cancer. The localization of PIVKA-II and AFP in gastric cancer cells was demonstrated by the immunostaining method using monoclonal antibody. Taken together, these results indicate that cancer cells may produce PIVKA-II or AFP in this patient.

Biomarkers↗

Isolation of cDNAs encoding the catalytic domain of poly(ADP-ribose) polymerase from Xenopus laevis and cherry salmon using heterologous oligonucleotide consensus sequences.

We have isolated and sequenced cDNAs encoding the catalytic domain of poly(ADP-ribose) polymerase (PARP) from Xenopus laevis and Oncorhyncus masou (cherry salmon). The cDNAs were amplified by polymerase chain reaction using heterologous oligonucleotides corresponding to the conserved sequences of mammalian cDNAs as primers. The deduced amino acid sequences of Xenopus laevis and cherry salmon cDNA showed 84.4% and 75.6% similarities to that of human PARP, respectively. In both species, mRNA for PARP was identified as a single band of 4 kb, and PARP mRNA was abundant in ovary and brain. Thus, mixed oligonucleotide-primed amplification is a useful method in the cloning of cDNAs from different species, and the catalytic domain of PARP is conserved structurally among phylogenetically different species, suggesting an importance of poly(ADP-ribosyl)ation.

Amino Acid Sequence↗

In vitro B-mode ultrasonographic criteria for diagnosing axillary lymph node metastasis of breast cancer.

Axillary lymph node status is an important factor for staging and treatment planning in breast cancer. Our study was performed in vitro on a node-by-node basis to evaluate the ability of B-mode ultrasonographic images to distinguish metastatic from nonmetastatic nodes. Immediately prior to histologic examination, individual dissected axillary nodes were scanned in a water bath using a 10 MHz B-mode ultrasonographic transducer. Four B-mode features (size, circularity, border demarcation, and internal echo) were evaluated for their ability to distinguish metastatic from nonmetastatic lymph nodes. Lymph node metastasis was indicated by (1) a large size (i.e., a length of the longest axis of 10 mm or greater); (2) a circular shape (i.e., the ratio of the shortest axis to the longest axis between 0.5 and 1.0); (3) a sharply demarcated border compared with surrounding fatty tissue; and (4) a hypoechoic internal echo, with obliteration of the fatty hilum. The sensitivity and specificity were compared for all combinations of features. We examined 84 histologically characterized axillary nodes from 27 breast cancer patients, including 64 nonmetastatic and 20 metastatic nodes. Of the criteria cited, circular shape was the best single feature for distinguishing metastatic from nonmetastatic nodes (sensitivity, 65%; specificity, 73%). The best combination of sensitivity (85%) and specificity (73%) was obtained using the criterion that a lymph node contained cancer when at least three positive features were present. The present in vitro study demonstrated that the sensitivity and specificity of B-mode ultrasonography for diagnosing lymph node metastasis were lower than 90%. Therefore, B-mode ultrasonography may not be an optimal noninvasive screening method for diagnosing axillary lymph node metastasis in breast cancer patients, particularly under in vivo clinical conditions.

Adult↗

Enzyme-histochemical method for identification of lymphatic capillaries.

Using 5'-nucleotidase (5'-Nase)-alkaline phosphatase (ALPase) double staining, lymphatic capillaries and blood capillaries were distinguished histochemically on cold glycol methacrylate (JB-4) sections of monkey intestines, on the basis of both enzyme characteristics. The specificity of the 5'-Nase reaction was obtained by inhibiting nonspecific ALPase in the 5'-Nase incubation medium including L-tetramisole. This double staining method demonstrated satisfactory isolated visualization of 5'-Nase activity in lymphatic capillaries and of ALPase activity in blood capillaries under light microscopy. The intensity and localization of 5'-Nase activity on the walls of lymphatic capillaries were also determined by the lead-based method under transmission electron microscopy. The intense reaction products of 5'-Nase activity were predominantly deposited on the outer surface of the plasma membrane of the lymphatic endothelial cells.

5'-Nucleotidase↗

Clonidine effects on all-night human sleep: opposite action of low- and medium-dose clonidine on human NREM-REM sleep proportion.

Norepinephrine (NE) is considered to play a permissive role in the occurrence of rapid eye movement (REM) sleep. Clonidine is an NE alpha-2-receptor agonist, which has been considered to act mainly on the autoreceptors of presynaptic noradrenergic neurons to reduce their release of NE. However, previous studies of clonidine effects on REM sleep have produced controversial results and the effects of clonidine remain uncertain. To clarify the pharmacological effects of clonidine on human sleep, the sleep electroencephalograms (EEG) recorded from 15 young normal subjects after a single administration of either a low (25 micro g) or medium (150 micro g) dose of clonidine were examined, and fast Fourier transformation (FFT) spectral analyses of the C3-A2 EEG were performed. Low-dose clonidine significantly increased the amount of REM sleep and decreased the amount of non-REM (NREM) sleep during the second one-third of the drug nights compared to the corresponding hours of baseline night recordings. In contrast, medium-dose clonidine significantly decreased REM and increased NREM on drug nights compared to baseline nights in the entire night. The opposite actions of low and medium doses of clonidine on NREM-REM proportion may indicate that low-dose clonidine mainly affects the alpha-2-receptors on locus coeruleus-NE neurons presynaptically, reducing the release of NE, whereas medium-dose clonidine acts more post-synaptically.

Adrenergic alpha-2 Receptor Agonists↗