Survival after biochemical failure in prostate cancer treated with radiotherapy: Spanish Registry of Prostate Cancer (RECAP) database outcomes.

INTRODUCTION: The clinical course in patients with prostate cancer (PCa) after biochemical failure (BF) has received limited attention. This study analyzes survival time from recurrence, patterns of progression, and the efficacy of salvage therapies in patients treated with radical or postoperative radiotherapy (RT). METHODS: This is a multicenter retrospective comparative study of 1135 patients diagnosed with BF and treated with either radical (882) or postoperative (253) RT. Data correspond to the RECAP database. Clinical, tumor, and therapeutic characteristics were collected. Descriptive statistics, survival estimates, and comparisons of survival rates were calculated. RESULTS: Time to BF from initial treatment (RT or surgery) was higher in irradiated patients (51 vs 37 months). At a median follow-up of 102 months (14-254), the 8-year cause-specific survival (CSS) was 80.5%, without significant differences between the radical (80.1%) and postoperative (83.4%) RT groups. The 8-year metastasis-free survival rate was 57%. 173 patients (15%) died of PCa and 29 (2.5%) of a second cancer. No salvage therapy was given in 15% of pts. Only 5.5% of pts who underwent radical RT had local salvage treatment and 71% received androgen deprivation (AD) ± chemotherapy. The worst outcomes were in patients who developed metastases after BF (302 pts; 26.5%) and in cases with a Gleason > 7. CONCLUSIONS: In PCa treated with radiotherapy, median survival after BF is relatively long. In this sample, no differences in survival rates at 8-years have been found, regardless of the time of radiotherapy administered. AD was the most common treatment after BF. Metastases and high Gleason score are adverse variables. To our knowledge, this is the first study to compare outcomes after BF among patients treated with primary RT vs. those treated with postoperative RT and to evaluate recurrence patterns, treatments administered, and causes of death. The results allow avoiding overtreatment, improving quality of life, without negatively affecting survival.

Protective effect of Ginkgo biloba extract on liver damage by a single dose of CCl(4) in male rats.

Functional and morphological alterations were generated by p.o. (per os) administration of a single oral dose of carbon tetrachloride (CCl(4); 0.125 mL/kg b.w., equivalent to 293 mg/kg) to adult male Wistar rats. CCl(4) significantly increased (p < 0.05) the serum activities of alanine aminotransferase (ALT; 7478 ± 1044%) and aspartate aminotransferase (AST; 6964 ± 833%), compared to control rats; CCl(4) also significantly decreased serum concentration of albumin (23 ± 5.5%) and increased the concentration of malondialhdeyde (MDA) in liver (300 ± 33%). Furthermore, CCl(4) down-regulated the mRNA steady-state level of tumor necrosis factor a(TNF-a). CCl(4) produced necrosis in the central lobe area, extended to the periphery, nuclear alterations (pycnosis, karyolysis and karyorrhexis), and cytoplasmic acidophilia. The pretreatment with 4 mg/kg (p.o.) of Ginkgo biloba extract (GbE), for 5 days, prevented most of the damage caused by CCl(4): significantly decreased the serum activities of ALT and AST (54 and 65%, respectively), compared to CCl(4)-treated rats; GbE partially prevented the increase of liver MDA (55 ± 14%) and the decrease of albumin concentration to 12 ± 0.2%. This pretreatment prevented the down-regulation of TNF-a and up-regulated the interleukine 6 (IL-6) mRNA steady-state level. Moreover, the GbE reduced the amount of necrotic areas in the central lobe area, compared to CCl(4)-treated rats.

Genetic diversity analysis of common beans based on molecular markers

A core collection of the common bean (Phaseolus vulgaris L.), representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico) Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions) was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each), as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP) +3/+3 primer combinations and seven simple sequence repeats (SSR) loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA) and molecular variance (AMOVA) analyses. AFLP analysis produced 530 bands (88.5 percent polymorphic) while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus). AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

The ATP levels in kidneys and blood are mainly decreased by acute ingestion of tullidora (Karwinskia humboldtiana).

Our previous acute toxicity studies with Karwinskia humboldtiana (Kh) in rats showed renal hemodynamic changes with a marked increase in the fractional excretion of sodium and morphological damage. To analyse the effects of Kh or 'tullidora' on energetic metabolism, a single dose of an oral preparation from the seed fruits was given to Wistar rats (1.25 g/kg). In tullidora-treated rats there was 8% mortality. ATP concentrations in renal tissue decreased significantly (control: 53.85+/-3.34, tullidora 38.28+/-5.31 micromol/g fresh tissue, P<0.05). Total blood (54.8+/-0.96, tullidora: 40.2+/-1.55 micromol/dL, P<0.01) and haemoglobin-ATP concentrations (3.69+/-0.12, tullidora: 2.56+/-0.11 micromol/g, P<0.01) were also significantly diminished. Moreover, the total protein in renal cortex from tullidora-treated rats decreased as compared to control group (control: 71.43+/-2.88, tullidora: 55.20+/-4.06 mg/g fresh tissue, P<0.05). In contrast, Na+-K+-ATPase activity in tullidora-treated animals was not different from control rats. These findings might partially explain the acute effects and mortality observed in the Kh treated rats.

Pathologic rupture of the spleen during induction with ATRA in a patient with acute promyelocytic leukemia.

Pathological rupture of the spleen is a rare but well recognized complication in hematological malignancies. Early clinical recognition of this life-threatening complication is necessary for rapid intervention. Here, we report on the case of a 26-year-old woman with acute promyelocytic leukemia who presented rupture of the spleen on day +2 of treatment with ATRA plus idarrubicin. In patients with acute leukemia, the presence of a painful abdomen and a sudden drop in hemoglobin levels, should alert of a possible splenic rupture, even without additional symptoms. This would facilitate an early treatment intervention with no modification to the chemotherapy schedule.

Synthesis and antineoplastic activity of cyclolignan aldehydes.

Several aldehydes related to methyl 9-deoxy-9-oxo-alpha-apopicropodophyllate, a selective antitumour agent against the HT-29 colon carcinoma, have been prepared and evaluated for their cytotoxic activities on four neoplastic cell lines (P-388, A-549, HT-29 and MEL-28). All of them lacked the lactone ring but maintained their cytotoxicity at, or under, the microM level.

DNA unpacking in guinea pig sperm chromatin by heparin and reduced glutathione.

The kinetics of nuclear decondensation and DNA unpacking induced by the action of a physiological concentration of heparin and glutathione of guinea pig spermatozoa was studied. Sperm (acrosomeless) suspensions were incubated at several different temperatures (37, 40, 43, and 46 degrees C), with a constant concentration of either heparin (50 microM) or reduced glutathione (12.5 mM) and increasing concentrations of the other reagent. Nuclei spermatozoa remained highly condensed when incubated in the medium alone or in either GSH or heparin alone for up to 72 h. Swelling of nuclei spermatozoa was initially observed during the first 20 min of incubation. The sperm nuclei initiate decompaction at the central part of the nuclear structure while at the periphery there remain numerous residues of densely packed chromatin. The swollen chromatin pattern presents the characteristic organization into "hub-like" nuclear bodies that measured 10-100 nm diameter joined by a network of chromatin fibers. At full nuclei decondensation chromatin end fibers are loose, probably meaning that DNA is not organized into loop domains. DNA presence was verified by the use of ethidium bromide and acridine orange.

Effect of heparin-reduced glutathione on hamster sperm DNA unpacking and nuclear swelling.

This study examined the kinetics of sperm nuclear decondensation induced by the action of physiological concentrations of heparin and glutathione in hamster sperm nuclei as a chromatin model that contains protamine P1 and P2. Sperm suspension was incubated at different temperatures (37, 40, 43, and 46 degrees C) in media, keeping constant the concentration of either heparin or GSH and increasing concentrations of the other reagent. Spermatozoa nuclei without any treatment, incubated for 72 h, appear densely condensed. Swelling of hamster spermatozoa nuclei was observed after 30 min of incubation in the presence of efficient concentrations of heparin-GSH. The extent of this time lag was significantly reduced at higher temperatures. DNA presence was verified by the use of ethidium bromide, acridine orange, and Feulgen stain. Phase-contrast microscopy shows that nuclear decondensation begins at the equatorial levels, with DNA highly condensed at the acrosome pole, and the basal pole as the DNA attachment point. Electron microscopy observations showed that hamster sperm nuclei initiates its decompaction at the peripheral regions and this behavior remains until late stages of decondensation, nevertheless, the chromatin is organized into "hub-like" nuclear bodies that measured 10-100 nm in diameter, joined by a network of chromatin fibers with apparent reduction in number. At the decondensation full stage, the network seems to be wide open with a reduced number of hub-like nuclear bodies present in the interlace. DNA is not organized into topologically constrained loop domains and is attached to the basal plate instead of to the nuclear matrix or any other structure.

Differential decondensation of class I (rat) and class II (mouse) spermatozoa nuclei by physiological concentrations of heparin and glutathione.

The kinetics of sperm nuclear decondensation induced by the action of physiological concentrations of heparin and glutathione was studied by comparing two rodents: the rat, with very stable protamine P1 containing chromatin (class I nuclei), and the mouse, with protamine P1 and protamine P2 (class II nuclei). Sperm suspensions were incubated at different temperatures (37, 40, 43, and 46 degrees C) in media while keeping a constant concentration of either heparin or GSH and increasing concentrations of the other reagent. Spermatozoa nuclei without any treatment incubated for 72 h appear densely condensed. Swelling of mouse spermatozoa nuclei was observed after 30 min of incubation in the presence of efficient concentrations of heparin-GSH. The extent of this time lag was significantly reduced at higher temperatures. This behavior was also observable in the rat, but required time lags of 3-4 h. Electron microscopy observations showed that the pattern of nuclear decondensation was different in both animal species. Mice sperm nuclei initiates its decompaction by the peripheral regions and this behavior remains until late stages of decondensation. On the contrary, rat spermatozoa nuclei decondense initially at the central part of the nuclei while the periphery remains condensed, showing numerous residues of densely packed chromatin. In both cases, the chromatin is organized into "hub-like" nuclear bodies joined by a network of chromatin fibers.

Synthesis and evaluation of pyrazolignans. A new class of cytotoxic agents.

A series of fused pyrazole derivatives of cyclolignans have been prepared through simple chemical routes and evaluated for their cytotoxic activities in culture cells of P-388 murine leukemia, A-549 lung carcinoma and HT-29 colon carcinoma. Despite the lack of the lactone moiety in their structures, they show IC50 values at microM levels.

Histiocytic cytophagic panniculitis: a rare late complication of allogeneic bone marrow transplantation.

Histiocytic cytophagic panniculitis (HCP) is the name given to the hemophagocytic syndrome when subcutaneous fat is involved. Histologically, it is characterized by phagocytosis of blood elements by histiocytes that appear to be benign. We report this rare skin disease in a 46-year-old patient that occurred 32 months after an allogeneic bone marrow transplantation. This skin disease could be a manifestation of graft-versus-host disease, although the connection remains speculative.

Energy metabolism of spermatozoa during pronucleus formation induced in vitro by heparin-reduced glutathione. I. Glucose uptake.

Glycolitic metabolism under basal conditions and its modifications by the combined action of heparin and GSH were studied in human sperm. Respirometric data indicated that the amount of U. L. [14C]-glucose converted to 14CO2 increased with the incubation time, being almost linear for up to 60 min and then leveling off at 120 and 150 min (594 and 620 nmol of [14C]-glucose/10(8) spermatozoa, respectively). When spermatozoa were incubated in the presence of heparin-GSH such behavior completely changed, showing a decrease (approximately 50%) in glucose metabolism with values of 254 and 366 nmol of [14C]-glucose/10(8) spermatozoa at the same incubation times as the basal consumption. When these results were compared with the kinetic of the swollen nuclei it was seen that at 30 min 44% of the spermatozoa have its nuclei swollen with a glucose uptake value of 91 nmol/10(8) spermatozoa, and at 150 min when nearly all the spermatozoa nuclei are swollen (95%) the glucose uptake increases fourfold more than the initial rate at 30 min. Therefore, it is possible to suggest the existence of an energy contribution by the sperm to the male pronuclei formation mechanism.

[Design of an expert system for decision-making in an emergency situation]. / Diseño de un sistema experto para toma de decisiones en situación de urgencia.

OBJECTIVES: To study the clinical applicability of the expert system URGSANT as a help in making up decisions in emergencies. MATERIAL AND METHODS: URGSANT is an expert system implemented in INSIGT 2+ which is structured in a modular and hierarchical form. It contemplates 44 urgent situations relating to the central nervous system, hematopoietic, cardiovascular, respiratory, gastrointestinal, genitourinary, endocrinological, and miscellaneous group. Validation of the program was made by four anesthesiologists who evaluated the performance of the program in 25 emergency cases and in 25 other situations that were treated by other specialists. RESULTS: The rationale of the system was basically correct. In most cases the program was considered efficient or very efficient during the different clinical situations and only in one case its guidance was wrong. CONCLUSIONS: The URGSANT expert system is an efficient and useful method for the clinician during emergency situations.

[The first operations performed with chloroform in Spain. More facts and new contributions]. / Las primeras operaciones efectuadas con el cloroformo en España. Más datos y nuevas aportaciones.

Although the issue of clinical introduction of chloroform in Spain was rather controversial, we can assure now with no doubt that first news of its discovery reached our country by the end of November and beginning of December of 1847. The cities first receiving those first news were Cádiz, Madrid, Barcelona, and Santiago de Compostela; in the latter two cities, during the first days of December, the new anesthetic agent was already available and the first experiments on dogs were conducted in 19th Sunday and first clinical assays in Barcelona and in Santiago de Compostela, the first experiments in Spain, were carried out in December 20th. Spanish scientific and daily press, particularly, press of Barcelona and Madrid promptly reflected the events and informed their readers about the discovery of chloroform as anesthetic. Our research deals with some of these aspects and we believe that will contribute to clarify not fully studied points to date.

[Non-traumatic rupture of the spleen in malignant hemopathies. 2 new cases]. / Rotura no traumática del bazo en hemopatías malignas. Dos nuevos casos.

Spontaneous splenic rupture is an unusual complication of hematologic malignancies with a high mortality rate. We report two cases of non-traumatic splenic rupture: the first one was a patient with myelomonocytic leukaemia and the second one a previously undiagnosed patient with non Hodgkin's lymphoma, both of them survived after splenectomy. Emphasis on the necessity of an early diagnosis and treatment are made.

Plasma levels of praziquantel decrease when dexamethasone is given simultaneously.

Treatment with praziquantel for neurocysticercosis frequently induces adverse reactions due to acute destruction of parasites; these reactions are suppressed by dexamethasone therapy. However, there is controversy about the most appropriate regimen with praziquantel and dexamethasone. We studied plasma levels of praziquantel in eight patients given the drug alone or with dexamethasone. Plasma levels of praziquantel were 50% lower in the same patient when dexamethasone was given simultaneously. Dexamethasone should not be added to praziquantel therapy as preventive treatment, but should be reserved for transient therapy of adverse reactions.