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Biomedical subjects

A Miguel

Publications and source records attributed to A Miguel.

At least 19 recordsLinked to original sources
PubMed2006

Classification and scoring systems in myelodysplastic syndromes: a retrospective analysis of 311 patients.

The main objective of this study was to evaluate the role of the recent World Health Organization (WHO) classification for assessing prognosis in patients with myelodysplastic syndromes (MDS). To this effect, we analyzed the prognostic impact of the WHO and French-American-British (FAB) morphologic classifications and of four different scoring systems in a series of 311 patients with primary MDS diagnosed between October 1990 and June 2001. Both the FAB and WHO classifications identified groups with different prognoses (p<0.0001), those presenting refractory anemia (RA) and refractory anemia with ringed sideroblasts (RARS) showing the best prognosis. The WHO classification subdivided RA into RA with only red cell dysplasia, and refractory cytopenia with multilineage dysplasia (RCMD), and RARS into RARS plus refractory cytopenia with multilineage dysplasia and ringed sideroblast (RCMD-RS). In our population, we have shown that the two subtypes characterized by dysplasia affecting exclusively the erythroid population (RA and RARS) have a better prognosis, with a median survival of 122.2 and 81.9 months, respectively, than those with multilineage dysplasia (RCMD and RCMD-RS) with a median survival of 32.3 and 43.2 months, respectively. There were no significant differences in median survival comparing RA with RAS (p<0.95), or comparing RCMD with RSCMD (p<0.97). Besides, the four scoring systems discriminated our MDS patients in terms of survival, and an increase in prognostic capacity was achieved on adding the score to the morphological classifications. Risk scoring had a greater prognostic impact than the FAB and WHO classifications. Prognostic scoring systems may be an important tool for risk stratification in hematological practice, and add significance to morphological classification. Combined application of the WHO classification and score system is useful for improving the identification of patients with a poorer prognosis. The WHO classification establishes more homogeneous subcategories than the FAB classification and is also able to identify groups with different prognoses.

Adult↗
PubMed2006

[Effect of oxidative stress in patients with chronic renal failure].

BACKGROUND: Cardiovascular disease remains the single most common cause of excess morbidity and mortality in end-stage renal disease (ESRD) patients and the traditional risk factors can't explain the high incidence of these events. New "non-traditional" risk factors are analysed in uremic patients and the increased oxidative stress is postulated to be an important contributor to uremic cardiovascular risk. METHODS: In order to evaluate the effects of the hemodialysis treatment, a complete oxidative stress study was performed in fifteen uremic patients. Representative antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), together with oxidized/reduced glutathione ratio (GSSG/GSH) and other oxidation indicators including malondialdehyde (MDA) and 8-oxo-2'-deoxyguanosine (8-oxo-dG), were analysed to assess oxidative stress status in normal control volunteers and in uremic patients treated with hemodialysis (HD). In the latter group blood samples were taken prior and after HD to evaluate the effect of the session of HD over the oxidative markers. RESULTS: Low levels of antioxidant enzyme activities were observed in the uremic patients as compared with normal control subjects. HD treatment results in a significant recovery of these enzyme activities but remain lower as compared with control values. Levels of GSSG and GSH concentrations were increased and reduced respectively in uremic patients. These differences were even higher before the HD and were reduced upon treatment to levels closer to those observed in controls. MDA levels and 8-oxo-dG levels were also increased in uremic patients with the highest values observed in the pre-treated HD group. Even though HD treatment decreases the levels of oxidation products in mononuclear cells of uremic patients the values of the control group are not reached. CONCLUSIONS: Our results suggest that hemodialysis by itself could correct the oxidative status in these patients. The possible mechanisms involved in the oxidative stress changes with the hemodialysis treatment will be discussed below.

Adult↗
PubMed2006

[Guidelines of the Spanish Society of Nephrology. Clinical practice guidelines for peritoneal dialysis].

In Spain and in each of its autonomous communities, the dialysis treatment of chronic renal disease stage 5 is totally covered by public health. Peritoneal dialysis, in any of its modalities, is established as the preferred home dialysis technique and is chosen by high percentage of patients as their choice in dialysis treatment. The Spanish Society of Nephrology has promoted a project of creation of performance guides in the field of peritoneal dialysis, entrusting a work group composed of members of the Spanish Society of Nephrology a with the development of these guides. The information offered is based on levels of evidence, opinion and clinical experience of the most relevant publications of the topic. In these guides, after defining the concept of << peritoneal dialysis>>, the obligations and responsibilities of the sanitation team of the peritoneal dialysis unit are determined, and protocols and performance procedures that try to include all the aspects that concern the patient with chronic renal disease in substitute treatment with this technique are developed. They propose prescription objectives based on available clinical evidence and, lacking this, on the consensus of the experts' opinions. The final aim is to improve the care and quality of the of the patient in peritoneal dialysis, optimizing in this way the survival of the patient and of the technique. In Spain, as in other neighbouring countries, peritoneal dialysis has an incidence and prevalence that is much lower than that of hemodialysis, ranging in the last evaluation by the Spanish Society of Nephrology between 5 and 24% in the different autonomous communities. The great majority of peritoneal dialysis units form part of the public network of the Spanish state, with special representation as a Satellite Unit or Concerted Center related to the public hospital of reference, on which it must depend.

Humans↗
PubMed2005

[Fungal peritonitis episodes in a peritoneal dialysis centre during a 10-year period: a report of 11 cases].

Fungal peritonitis is a rare cause of peritonitis, but it is associated to poorer prognosis and higher mortality than bacterial peritonitis. Until now, predisposing factors and treatment have not been well established. We retrospectively reviewed all the cases of fungal peritonitis diagnosed for ten years in 218 patients undergoing continuous ambulatory peritoneal dialysis. In all we detected 11 episodes of fungal peritonitis in 11 patients, that means the 4% of continuous ambulatory peritoneal dialysis peritonitis. All the cases of fungal peritonitis were caused by Candida species. As a result of fungal peritonitis 36% of the patients died, 55% had to change to long-term hemodialysis because of failure in peritoneal dialysis technique. Only one case (9%) managed to continue peritoneal dialysis. The factors associated with the development of fungal peritonitis were: the presence of antibiotic use within 1 month before fungal peritonitis, patient older than 70 years old, low levels in albumine plasmatic and long permanence in continuous ambulatory peritoneal dialysis. The treatment consisted in intraperitoneal fluconazol combined with oral 5-flucytosine for 4 to 6 weeks. In the two last cases we associated intravenous caspofungine too. Given that no improvement was seen within 72 hours of treatment, the catheter must be removed in all the cases.

Administration, Oral↗
PubMed2004

Sepsis and SOFA score: related outcome for critically ill renal patients.

AIMS: To evaluate the influence of sepsis in critically ill patients with acute renal failure (ARF), and to analyze the value of the sequential organ failure assessment (SOFA) score for assessing the morbidity and related mortality of these patients. MATERIAL AND METHODS: A prospective observational study developed in a medical intensive care unit (ICU) of a tertiary care university hospital. Data were collected from January 1, 2001 - July 31, 2002. The inclusion criterion was either a creatinine plasma level > or = 2 mg/dl on ICU admission or increases > or = 30% from its initial value. Sepsis was evaluated at the time of study inclusion, and patients were distributed into 2 groups (septic and nonseptic patients). RESULTS: Two hundred patients with ARF were prospectively enrolled in the study (91 (45.5%) septic and 109 (54.5%) nonseptic patients). Median age was 68 years in septic patients and 72 in nonseptic ones while the percentage of males in both groups was 66% vs 69%, respectively. Septic patients showed more organ failures and more respiratory, cardiovascular and coagulation failures at the time of study admission as well as a worse mean SOFA score during the first 4 days after inclusion (p < 0.01). Mortality rate at the ICU was significantly higher in the septic group when compared to the nonseptic one (55% vs 19.3%, OR = 2.21 (1.65 - 2.97)). Using stepwise logistic regression, acute tubular necrosis and oliguria in septic patients as well as cardiovascular failure (evaluated by SOFA score) in nonseptic patients were identified as independent risk factors for mortality. CONCLUSIONS: Septic and nonseptic ICU patients with ARF have an increased risk of ICU mortality depending on the type of organ failure. Although SOFA score does not predict outcome, it is a useful tool to categorize these patients and to describe a sequence of complications in critically ill patients.

Acute Kidney Injury↗
PubMed2004

[Hypokalemic metabolic alkalosis: apropos of a case of Gitelman's syndrome].

We present a case of Gitelman's Syndrome in a 20 year-old woman who came to our service with weakness, asthenia, leg cramps and tetany. Laboratory studies revealed metabolic alkalosis with hypokalemia, hypomagnesemia and low calcium in a 24-hour urine test. The diagnosis of this syndrome is made in some cases during adult life because this syndrome is asymptomatic over several years. Gitelman's Syndrome is autosomal recessive as is Bartter's Syndrome. The gene is located in chromosome 16q, which encodes the cotransporter Na/Cl sensitive to thiazide in the distal convoluted tubule. The defect of cotransporter produces an alteration of sodium reabsorption that causes electrolytic disorders typical of this Syndrome and different from Bartter's Syndrome. The typical electrolytic alterations are hypocalciuria and hypomagnesemia secondary to high urinary magnesium excretion. The prognosis of this syndrome is excellent and treatment consists in correction of serum electrolytes with oral administration of magnesium and potassium. In spite of this treatment, in some cases it is very difficult to reach normal serum levels of magnesium because of the high doses of oral magnesium, which produce common crises of diarrhea that increase magnesium gastrointestinal losses.

Alkalosis↗
PubMed2003

A randomized study of intermediate as compared with high doses of interferon-alpha for chronic myeloid leukemia: no differences in cytogenetic responses.

Interferon-alpha (IFN-alpha) is a therapy of unquestionable efficacy in chronic myeloid leukemia (CML) patients. The best dose of IFN-alpha in the treatment of CML still remains controversial. Our primary objective was to compare cytogenetic responses in patients treated with intermediate versus high doses of IFN-alpha. A multicenter randomized controlled trial was conducted involving 109 patients with untreated CML in chronic phase from 26 Spanish hospitals. Patients were assigned to receive either an intermediate (2.5 MU/m(2) per day) or high (5 MU/m(2) per day) target dose of IFN-alpha. Hydroxyurea was allowed in both groups. In total, 108 patients were analyzed, 53 in the intermediate- and 55 in the high-dose group. Median follow-up was 47.5 months. The dose of IFN-alpha actually given was lower in the intermediate-dose group (3.83 MU/day) than in the high-dose group (6.6 MU/day) ( p<0.001). The rate of complete cytogenetic response was 24.5% in the intermediate- and 12.7% in the high-dose group (NS). A partial cytogenetic response was obtained in 7.5% and 10.9%, respectively. Cox analysis did not reveal any influence of the randomization arm on cytogenetic response rate. Ten patients in each group discontinued IFN-alpha because of toxicity. Albeit not our primary objective, no differences were found in terms of survival or transformation rate between both groups. Median survival was 73 months; 64% of patients remained free of transformation at 5 years. In terms of cytogenetic response, intermediate doses of IFN-alpha are as effective as high doses in the treatment of CML.

Adult↗
PubMed2002

[Analysis of survival in dialysis: hemodialysis versus peritoneal dialysis and the significance of comorbidity].

To choose the best possible dialysis technique for those patients with end-stage renal disease continues to be a matter of debate. Even after putting aside the evident influence that economic and geographic factors as well as the health politics may have in the selection of the technique, different studies comparing survival between hemodialysis (HD) and peritoneal dialysis (PD) have shown contradictory results which could be explained by the differing methodological and statistical methods used together with the different influence assigned to the comorbidity found when starting the treatment, a situation that has increased the confusion about this topic. Based on this we performed a retrospective analysis with a follow-up time of seven years including all those patients who started dialytic treatment in our area, with a final number of 3.106 hemodialysis patients and 542 peritoneal dialysis patients. Those patients who were transferred to another treatment technique during the time of the study were excluded. Age higher than 70 years, cardiovascular disease, liver disease, diabetes mellitus and the presence of dyslipidemia were included as comorbidity factors. Peritoneal dialysis patients were younger than those treated by hemodialysis (54.53 vs 60.1 years), but suffered from higher cardiovascular comorbidity and were more often diabetic. The global survival was the same in both groups up to 32 months of treatment. Although no differences were found when comparing those patients without comorbidity factors, those with comorbidity had better survival on hemodialysis. Age higher than 70 years was the only comorbidity factor with statistically significant difference for a better survival in hemodialysis.

Adolescent↗
PubMed2001

A predictive formula of the contraction stress in restorative and luting materials attending to free and adhered surfaces, volume and deformation.

OBJECTIVES: To find a predictive formula of stress, considering the surfaces (free, adhered) involved, the volume and characteristics of material and the deformation of the measuring system. MATERIALS AND METHODS: 231 samples of five chemically cured restoratives (Silar (SIL, 23), Clearfil F2 (CLE, 39), P10 (P10, 33), Concise (CON, 30), Isopast (ISO, 28)) and four luting (3M Experimental 241 (EXM, 20), Variolink II (VAR, 13), Vitremer LC (VTM, 20) and Dyract Cem (DYR, 25)) materials were allowed to polymerize until they reached a maximum tension (T(max), 25 min) between six pairs (null 5.81, 8.5, 11.26, 12.42, 17.02, 23.14 mm) of polished metallic discs (range of distances: 0.02-5.9 mm) mounted in a tension machine. The deformation of the measuring system was measured for the recorded forces. RESULTS: A descriptive non-linear formula T(max)=KVol(-3.267)FS(3.283)AS(0.642)Def(0.561) was found that individualizes the material's characteristics (K) that considers volume (Vol), free (FS) and adhered (AS) surfaces and deformation (Def) of the system for each force. This formula renders good correlation (material K (r(2) coefficient)): SIL 0.9998 (0.995), CLE 1.0062 (0.989), P10 1.0224 (0.990), CON 0.9908 (0.992), ISO 0.9648 (0.974), EXM 1.0083 (0.991), VAR 0.9777 (0.996), VTM 0.9925 (0.993), DYR 0.9971 (0.997) between actual T(max) and calculated Tension. There are statistically significant differences (p=0.002) between K values of both (restorative and luting) groups. SIGNIFICANCE: Predictive parameters have influence in a different way to what is actually considered, if the system is allowed to have deformation, as occurs naturally and volume and material's characteristics are considered.

Acrylic Resins↗
PubMed2001

Porosity of resin cements and resin-modified glass-ionomers.

PURPOSE: To quantify the internal free surface in various resin cements and glass-ionomer-based materials. MATERIALS AND METHODS: Materials tested were Nexus fluid (NXF) and viscous (NXV), Vitremer (VTM), Fuji II LC (FII), Vitremer Luting Cement (VLC), Dyract (DYR) and Compoglass (COM). Samples (n=5) were made of each material between two microscopic glass slides under same weight. With a transmitted light microscopy, four zones of each sample were evaluated, finding the number of porosities per mm2 (NP), the average radius of porosities (RP), the ratio of total area of surface porosities (micron2) to area (mm2) of specimen surface (TA) and the ratio of total volume of porosities (micron2) to area (mm2) of material surface (VP). RESULTS: Median test was used. NP: NXV, NXF and DYR had smaller NP than VTM and FII and (likely) than VLC (P> 0.0000001). RP was smaller for DYR than for VLC and (likely) than for NXV (P= 0.00019). TA: NXV, NXF and DYR had smaller TA than VTM, FII and VLC (P< 0.0000001). VP: NXV and DYR had smaller VP than FII and (likely) than VTM and VLC (P< 0.0000001).

Chi-Square Distribution↗
PubMed2000

Induction of heme oxygenase-1 expression in macrophages by diesel exhaust particle chemicals and quinones via the antioxidant-responsive element.

Diesel exhaust particles (DEP) contain organic chemicals that contribute to the adverse health effects of inhaled particulate matter. Because DEP induce oxidative stress in the lung and in macrophages, effective antioxidant defenses are required. One type of defense is through the expression of the antioxidant enzyme, heme oxygenase I (HO-1). HO-1 as well as phase II detoxifying enzymes are induced via antioxidant response elements (ARE) in their promoters of that gene. We show that a crude DEP total extract, aromatic and polar DEP fractions, a benzo(a)pyrene quinone, and a phenolic antioxidant induce HO-1 expression in RAW264.7 cells in an ARE-dependent manner. N-acetyl cysteine and the flavonoid, luteolin, inhibited HO-1 protein expression. We also demonstrate that the same stimuli induce HO-1 mRNA expression in parallel with the activation of the SX2 enhancer of that gene. Mutation of the ARE core, but not the overlapping AP-1 binding sequence, disrupted SX2 activation. Finally, we show that biological agents, such as oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine, could also induce HO-1 expression via an ARE-dependent mechanism. Prior induction of HO-1 expression, using cobalt-protoporphyrin, protected RAW264.7 cells against DEP-induced toxicity. Taken together, these data show that HO-1 plays an important role in cytoprotection against redox-active DEP chemicals, including quinones.

Acetylcysteine↗
PubMed2000

Can the creatinine dialysate-to-plasma ratio from the peritoneal equilibration test be replaced by the sodium dialysate-to-plasma ratio and the sodium level in the dialysate?

The peritoneal equilibration test (PET) is a useful tool that categorizes peritoneal transport. However, the method has some inconveniences. Some authors suggest that measuring the sodium level in the dialysate (NaD) or the dialysate-to-plasma ratio for sodium (D/PNa) can substitute for the PET. We applied a mathematical analysis [Fisher intraclass correlation coefficient (FICC)] to 43 PETs performed in 43 peritoneal dialysis patients (29 males, 14 females) with a mean age of 55.3 years (range: 28-85 years). Determinations of NaD, of sodium level in plasma (NaP), and of D/PNa at times 0, 30, 60, 120, and 240 minutes were added to the usual PET determinations. After using the NaD240 and the D/PNa240 values to calculate the cut-off values for the various peritoneal transport categories, we obtained a transport distribution very similar to that of the PET dialysate-to-plasma ratio for creatinine after 240 minutes (D/PCr240). At the same time, the FICC showed good (0.69) and excellent (0.77) correlation of NaD240 and D/PNa240 respectively with the D/PCr240. Therefore either of these two methods, which are cheaper and quicker than a PET, can be used to categorize peritoneal transport with a high degree of reliability.

Adult↗
PubMed2000

A prospective multicenter comparison of peritonitis in peritoneal dialysis patients aged above and below 65 years. Levante PD Multicenter Group.

Various authors have found peritonitis rates in older peritoneal dialysis (PD) patients to be higher, similar, or even lower when compared to rates in younger populations. We prospectively analyzed all episodes of peritonitis registered in the 381 patients (219 males, 162 females; mean age, 55.5 +/- 17.0 years) who were treated with PD during four years (1993-1996) in our multicenter group. Patients were distributed into two groups. Group A included 138 patients aged 65 years or over (mean age: 72.3 +/- 5.1 years); group B included 243 patients aged below 65 years (mean age: 46.0 +/- 13.6 years). No differences were seen in general PD characteristics. Normalized protein catabolic rate (nPCR) was higher in younger patients (p = 0.001). Patients in group A experienced more peritonitis (135 episodes; 1 episode per 16.7 patient-months) than patients in group B (198 episodes; 1 episode per 21.7 patient-months; p = 0.01). Although no differences were seen in the general characteristics of the peritonitis episodes, gram-negative peritonitis and peritonitis not achieving a cure were more commonly secondary to enteric bacteria in group A (p = 0.03). We conclude that PD patients aged 65 years or over are at higher risk of peritonitis. Also, in this age group, gram-negative peritonitis and peritonitis with any evolution except cure are more likely to be due to enteric bacteria.

Age Factors↗
PubMed1999

Delta9-tetrahydrocannabinol induces apoptosis in human prostate PC-3 cells via a receptor-independent mechanism.

The effect of delta9-tetrahydrocannabinol (THC), the major psycho-active component of marijuana, in human prostate cancer cells PC-3 was investigated. THC caused apoptosis in a dose-dependent manner. Morphological and biochemical changes induced by THC in prostate PC-3 cells shared the characteristics of an apoptotic phenomenon. First, loss of plasma membrane asymmetry determined by fluorescent anexin V binding. Second, presence of apoptotic bodies and nuclear fragmentation observed by DNA staining with 4',6-diamino-2-phenylindole (DAPI). Third, presence of typical 'ladder-patterned' DNA fragmentation. Central cannabinoid receptor expression was observed in PC-3 cells by immunofluorescence studies. However, several results indicated that the apoptotic effect was cannabinoid receptor-independent, such as lack of an effect of the potent cannabinoid agonist WIN 55,212-2, inability of cannabinoid antagonist AM 251 to prevent cellular death caused by THC and absence of an effect of pertussis toxin pre-treatment.

Annexin A5↗
PubMed1999

Importance of residual renal function in continuous ambulatory peritoneal dialysis: its influence on different parameters of renal replacement treatment.

OBJECTIVE: To study the influence of residual renal function (RRF) on different parameters of the renal substitutive treatment offered by peritoneal dialysis. METHODS: We analyzed the impact of RRF on dialysis dose, nutrition parameters, anemia and phosphocalcic metabolism in 37 patients with end-stage renal disease (ESRD) treated by continuous ambulatory peritoneal dialysis (CAPD). Analytical controls were done every 6 months after an initial assessment at the end of the first month of treatment. Multiple lineal regression models were used as the statistical method to analyze the influence of RRF on different theoretically dependent factors. RRF was calculated as a mean of creatinine and urea clearances. Three observations per patient were used: one at the end of the first month of treatment; a final one at the end of follow-up (mean time 24.2 +/- 11.4 months), and at a mean time between them (13.4 +/- 6.7 months), with a final number of 111 observations. RESULTS: Dialysis dose: RRF was the most important factor in terms of creatinine clearance (r(2) = 0.94; beta = 0.999), KT/V (r(2) = 0. 68; beta = 0.819) and beta(2)-microglobulin levels (r(2) = 0.46; beta = -0.489). Nutrition parameters: RRF was a determinant factor for normalized protein catabolic rate (r(2) = 0.53; beta = 0.471), percent lean body mass (r(2) = 0.45; beta = 0.446) and albumin levels (r(2) = 0.25; beta = 0.229). Anemia: RRF was the most important factor when studying hemoglobin levels (r(2) = 0.28; beta = 0.407). Phosphocalcic metabolism: Between the analyzed factors, RRF was the only one which reached significance on serum phosphate levels (r(2) = 0.19; beta = -0.594). RRF did not show any relationship with either calcium or PTH levels. CONCLUSIONS: Independent of other factors, RRF in CAPD is positively and directly related to dialysis dose, beta(2)-microglobulin levels, nutrition parameters (albumin, normalized protein catabolic rate and percent lean body mass, hemoglobin and serum phosphate levels.

Anemia↗
PubMed1999

Stage, percentage of basophils at diagnosis, hematologic response within six months, cytogenetic response in the first year: the main prognostic variables affecting outcome in patients with chronic myeloid leukemia in chronic phase treated with interferon-alpha. Results of the CML89 trial of the Spanish Collaborative Group on interferon-alpha2a and CML.

BACKGROUND AND OBJECTIVE: Interferon-a (IFN) is increasingly being used as the drug of choice in chronic myeloid leukemia patients. The main objectives of the study were to study the influence of the classic prognostic variables and response to IFN, and to assess the influence of this response on the course of the disease and survival. DESIGN AND METHODS: Single arm, prospective, multicenter study, without a control group. Only Ph1-positive CML patients were included. The treatment scheme was biphasic: the patients first received standard chemotherapy and thereafter IFN-a2a was used as monotherapy, with a target dose of 9 MU/d/s.c. RESULTS: Twenty-one centers in Spain enrolled 132 patients (72 men, 60 women). The median dose of IFN given was 5.8 MU/d, and the median treatment duration was 431 days (range: 18-2,597). Seventy-two percent of patients obtained a hematologic response in the first six months of IFN treatment. Genetic response was obtained in 47% of the patients, and the response was major or complete in 27% and 19%, respectively. The median time to obtain this response was 7, 9, and 18 months for minimal, partial and complete genetic response, respectively. Multivariant analysis showed that only a higher percentage of basophils at diagnosis was associated with a worse hematologic response at six months (p=0.001) (OR: 1.23) and with a worse cytogenetic response in the first year of IFN therapy (p=0.018) (OR: 1.4). Over an observation period of 8 years, 35.6% of the patients died, and 85 (64.4%) remained alive. With a median follow-up of 42 months (3.7-98), the 6-year projected probabilities of survival and transformation-free survival were 0.61+/-0.07 vs. 0.54+/-0.07, respectively. Patients with Kantarjian's stage 3 disease or in a high-risk Sokal group had lower probabilities of survival, but these systems did not adequately discriminate in our series. Obtaining a complete hematologic response in the first six months of IFN therapy was favorable in terms of overall survival (p=0.05; HR=0.33). Cox's analysis demonstrated that obtaining a cytogenetic response in the first year was independently associated with better overall survival (p=0.04; HR=0.19) and better transformation-free survival (p=0.0035; HR=0.11). INTERPRETATION AND CONCLUSIONS: Nearly half of the patients obtained some degree of Philadelphia suppression, which was major in 27%, and complete in 19%. A higher percentage of basophils at diagnosis was the only variable associated with a lower probability of cytogenetic response. Obtaining a cytogenetic response during the first year of IFN treatment was a favorable and independent variable in terms of survival and transformation-free survival. Obtaining a major cytogenetic response during this period decreased the risk of transformation twenty times. Our results suggest that the effect of IFN on survival is independent of the classic prognostic variables.

Adolescent↗
PubMed1998

Phase II study of estramustine and vinorelbine in hormone-refractory prostate carcinoma patients.

The purpose of this study was to evaluate the antitumor activity of vinorelbine and oral estramustine phosphate in patients with metastatic, hormone-refractory prostate cancer. We evaluated the activity of this association using the following schedule: estramustine phosphate 600 mg/m2/day orally days 1-42 and vinorelbine 25 mg/m1 days 1, 8, 22, 29 cycles repeated every 56 days. Twenty-five patients were included in the study, 24 being evaluable for response and 25 for toxicity. Out of 5 patients with measurable disease, none had an objective response. Of the 24 assessable patients with bone metastases, 9 patients had a > or = 65% decline in pretreatment prostate-specific antigen (PSA) level, stable disease was observed in 10 and 5 patients progressed. Toxicities were minimal. Anemia was observed in 5 patients, alopecia in 4 and nausea and vomiting was observed in 6 patients. Anorexia and weight loss of more than 10% were observed in 2 patients. This combination is active and well tolerated in hormone-resistant prostate cancer. These results support the therapeutic strategy of combining agents that impair microtubule function.

Adenocarcinoma↗