Risk of biochemical recurrence in patients with a positive surgical margin after radical prostatectomy.

INTRODUCTION: Serum prostate specific antigen (PSA) is an irreplaceable marker in the detection and follow-up of patients with prostate cancer. In our analysis we addressed factors that could indicate the likelihood of biochemical recurrence (BCR) early after radical prostatectomy. We mainly focused on the positive surgical margin (R1). METHODS: Retrospective evaluation and analysis of the database of patients with prostate cancer after radical prostatectomy from 2001 to 2019. In total 1529 patients were enrolled in the study. The median follow-up was 48 months. The age of the patients ranged from 49 to 76 years. We used pre-operative PSA values, and the monitoring of the dynamics of 3rd generation PSA progression (detection limit 0.003 ng/ml) at month 1 and month 3 after surgery and then in 3-month intervals. We monitored the surgical margin positivity (R0 negative, R1 positive) and the Gleason score (GS) based on histological samples and we analysed the relationship to biochemical recurrence of the disease. RESULTS: The pre-operative PSA value did not show a direct relationship to the R1 risk. Patient values in the groups R1 and R0 differed only by 1.159 ng/ml (p=NS). The 3rd generation PSA value at month 1 after surgery was 50.82% higher in R1 patients (p>0.001). 50% of patients with R1 (29.5% patients of the total) did develop BCR during the follow-up period, while in patients with R0 (70.5% patients of the total) this proportion was 30% (p>0.001). Among those with GS 67, 47% developed BCR. The GS 810 group relapsed in 75% of the cases (p>0.001). CONCLUSION: According to our analysis 33% of the patients reached the stage of biochemical recurrence. We demonstrated a direct dependency between the risk of recurrence and the final Gleason score. The presence of R1 should not be viewed as a direct indication for adjuvant radiotherapy.

Ferroelectret-based Hydrophone Employed in Oil Identification-A Machine Learning Approach.

This work focuses on acoustic analysis as a way of discriminating mineral oil, providing a robust technique, immune to electromagnetic noise, and in some cases, depending on the applied sensor, a low-cost technique. Thus, we propose a new method for the diagnosis of the quality of mineral oil used in electrical transformers, integrating a ferroelectric-based hydrophone and an acoustic transducer. Our classification solution is based on a supervised machine learning technique applied to the signals generated by an in-home built hydrophone. A total of three statistical datasets entries were collected during the acoustic experiments on four types of oils. The first, the second, and third datasets contain 180, 240, and 420 entries, respectively. Eighty-four features were considered from each dataset to apply to two classification approaches. The first classification approach is able to distinguish the oils from the four possible classes with a classification error less than 2%, while the second approach is able to successfully classify the oils without errors (e.g., with a score of 100%).

The Effect of Water Temperature during Cold-Water Immersion on Recovery from Exercise-Induced Muscle Damage.

This study investigated the effects of 5 and 15°C cold-water immersion on recovery from exercise resulting in exercise-induced muscle damage. 42 college-aged men performed 5×20 drop-jumps and were randomly allocated into one of 3 groups: (1) 5°C; (2) 15°C; or (3) control. After exercise, individuals from the cold-water immersion groups had their lower limbs immerged in iced water for 20 min. Isometric knee extensor torque, countermovement jump, muscle soreness, and creatine kinase were measured before, immediately after, 24, 48, 72, 96 and 168 h post-exercise. There was no between-group difference in isometric strength recovery (p=0.73). However, countermovement jump recovered quicker in cold-water immersion groups compared to control group (p<0.05). Countermovement jump returned to baseline after 72 h in 15°C, 5°C group recovered after 96 h and control did not recovered at any time point measured. Also, creatine kinase returned to baseline at 72 h and remained stable for all remaining measurements for 15°C group, whereas remained elevated past 168 h in both 5°C and control groups. There was a trend toward lower muscle soreness (p=0.06) in 15°C group compared to control at 24 h post-exercise. The result suggests that cold-water immersion promote recovery of stretch-shortening cycle performance, but not influence the recovery of maximal contractile force. Immersion at warmer temperature may be more effective than colder temperatures promoting recovery from strenuous exercise.

Role of Shp2 in forebrain neurons in regulating metabolic and cardiovascular functions and responses to leptin.

OBJECTIVE: We examined whether deficiency of Src homology 2 containing phosphatase (Shp2) signaling in forebrain neurons alters metabolic and cardiovascular regulation under various conditions and if it attenuates the anorexic and cardiovascular effects of leptin. We also tested whether forebrain Shp2 deficiency alters blood pressure (BP) and heart rate (HR) responses to acute stress. DESIGN: Forebrain Shp2(-/-) mice were generated by crossing Shp2(flox/flox) mice with CamKIIα-cre mice. At 22-24 weeks of age, the mice were instrumented for telemetry for measurement of BP, HR and body temperature (BT). Oxygen consumption (VO2), energy expenditure and motor activity were monitored by indirect calorimetry. RESULTS: Shp2/CamKIIα-cre mice were heavier (46±3 vs 32±1 g), hyperglycemic, hyperleptinemic, hyperinsulinemic and hyperphagic compared to Shp2(flox/flox) control mice. Shp2/CamKIIα-cre mice exhibited reduced food intake responses to fasting/refeeding and impaired regulation of BT when exposed to 15 and 30 °C ambient temperatures. Despite being obese and having many features of metabolic syndrome, Shp2/CamKIIα-cre mice had similar daily average BP and HR compared to Shp2(flox/flox) mice (112±2 vs 113±1 mm Hg and 595±34 vs 650±40 b.p.m.), but exhibited increased BP and HR responses to cold exposure and acute air-jet stress test. Leptin's ability to reduce food intake and to raise BP were markedly attenuated in Shp2/CamKIIα-cre mice. CONCLUSION: These results suggest that forebrain Shp2 signaling regulates food intake, appetite responses to caloric deprivation and thermogenic control of body temperature during variations in ambient temperature. Deficiency of Shp2 signaling in the forebrain is associated with augmented cardiovascular responses to cold and acute stress but attenuated BP responses to leptin.

Inhibition of soluble epoxide hydrolase reduces food intake and increases metabolic rate in obese mice.

BACKGROUND AND AIMS: This study evaluated the responses to soluble epoxide hydrolase (s-EH) inhibition, an essential enzyme in the metabolism of arachidonic acid, on food intake, body weight and metabolic parameters in mice fed a high fat-high fructose diet (HFD) for 10 weeks. METHODS AND RESULTS: After 5 weeks of HFD, mice were divided into two groups: 1) s-EH inhibitor (AR9281, 200mg/kg/day by gavage twice daily), and 2) vehicle (0.3ml per gavage). Food intake, body weight, oxygen consumption (VO(2)), carbon dioxide production (VCO(2)), respiratory quotient (RQ), and motor activity were measured weekly for more 5 weeks. HFD increased body weight (37±1 vs. 26±1g), and plasma of glucose (316±8 vs. 188±27mg/dl), insulin (62.1±8.1 vs. 15.5±5.0µU/ml), and leptin levels (39.4±3.6 vs. 7.5±0.1ng/ml) while reducing VO(2), VCO(2) and motor activity. s-EH inhibition for 5 weeks decreased caloric intake by ~32% and increased VO(2) by ~17% (42.8±1.4 vs. 50.2±1.5ml/kg/min) leading to significant weight loss. Inhibition of s-EHi also caused significant reductions in plasma leptin levels and visceral fat content. Uncoupling protein 1 (UCP1) content in brown adipose tissue was also elevated by ~50% during s-EH inhibition compared to vehicle treatment. CONCLUSION: These results suggest that s-EH inhibition with AR9281 promotes weight loss by reducing appetite and increasing metabolic rate, and that increased UCP1 content may contribute to the increase in energy expenditure.

The α2,3-selective potentiator of GABAA receptors, KRM-II-81, reduces nociceptive-associated behaviors induced by formalin and spinal nerve ligation in rats.

Clinical evidence indicates that positive allosteric modulators (PAMs) of GABAA receptors have analgesic benefit in addition to efficacy in anxiety disorders. However, the utility of GABAA receptor PAMs as analgesics is compromised by the central nervous system side effects of non-selective potentiators. A selective potentiator of GABAA receptors associated with α2/3 subunits, KRM-II-81(5-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepin-3-yl)oxazole), has demonstrated anxiolytic, anticonvulsant, and antinociceptive effects in rodents with reduced motoric side effects. The present study evaluated the potential of KRM-II-81 as a novel analgesic. Oral administration of KRM-II-81 attenuated formalin-induced flinching; in contrast, diazepam was not active. KRM-II-81 attenuated nociceptive-associated behaviors engendered by chronic spinal nerve ligation (L5/L6). Diazepam decreased locomotion of rats at the dose tested in the formalin assay (10 mg/kg) whereas KRM-II-81 produced small decreases that were not dose-dependent (10-100 mg/kg). Plasma and brain levels of KRM-II-81 were used to demonstrate selectivity for α2/3- over α1-associated GABAA receptors and to define the degree of engagement of these receptors. Plasma and brain concentrations of KRM-II-81 were positively-associated with analgesic efficacy. GABA currents from isolated rat dorsal-root ganglion cultures were potentiated by KRM-II-81 with an ED50 of 32 nM. Measures of respiratory depression were reduced by alprazolam whereas KRM-II-81 was either inactive or produced effects with lower potency and efficacy. These findings add to the growing body of data supporting the idea that α2/3-selective GABAA receptor PAMs will have efficacy and tolerability as pain medications including those for neuropathic pain. Given their predicted anxiolytic effects, α2/3-selective GABAA receptor PAMs offer an additional inroad into the management of pain.

Gravimetric composition of the rejects coming from the segregation process of the municipal recyclable wastes.

Rejects from selective collection are municipal solid waste (MSW) not used for recycling and are, therefore, destined for the landfill in Brazil. Knowledge of the composition and generation of this waste is important for strategically planning public policies that minimize its generation and its negative environmental impacts. However, this portion of MSW is not very well known. Therefore, the aim of this study was to analyze the rejects from the sorting process of the selective waste collection in the municipality of Blumenau, in the State of Santa Catarina, southern Brazil. The studied rejects came from the largest cooperative in the city, and its composition was sorted into 17 categories of 101 samples over the course of one year, with a total of 3893 kg of analyzed rejects. The waste collected by the selective collection of the municipality was evaluated monthly to determine which part of this quantity became rejects and to determine the composition and seasonality of these rejects. The study found that 30.5% of the waste sorted by the cooperative was rejected. Among these rejects, the presence of materials that could be marketed by the cooperative was verified. Hazardous and/or legally prohibited waste were also identified, as were organics, construction and demolition waste, health care waste, electronics, textiles, footwear, batteries, and bulbs. Seasonal analysis indicated a concerning constant generation of health care waste. Aside from that, there was an increase in the generation of waste from electrical and electronic equipment (EEE) during the Christmas period, when a large part of the population discards their EEE. This information is important for the enforcement of the MSW management structure as well as for educational campaigns aimed at the correct separation of waste that should be sent for selective collection.

Infrared single mode chalcogenide glass fiber for space.

An important measuring technique under study for the DARWIN planet finding mission, is nulling interferometry, enabling the detection of the weak infrared emission lines of an orbiting planet. This technique requires a perfect wavefront of the light beams to be combined in the interferometer. By using a single mode waveguide before detection, wavefront errors are filtered and a virtually perfect plane wavefront is obtained. In this paper the results on the development and the optical characterisation of suitable infrared transmitting chalcogenide glasses and mid-IR guiding optical fibers are reported. Two different perform techniques for manufacturing core-cladding chalcogenide fibers are described. Two types of step index fibers, prepared with Te(2)As(3)Se(5) chalcogenide glasses, offer single mode guidance at 10.6 mum.

Confounding factors in water EMG recordings: an approach to a definitive standard.

This work presents a study on the influence of the aqueous environment on the surface EMG (sEMG) signal recorded in bipolar montage from the abductor pollicis brevis muscle, when only the forearm is immersed in water. Ten men, 30.1+/-4.0 (mean +/- SD) years old, performed ten 2-s 40% MVC isometric contractions of the abductor pollicis brevis muscle in two controlled environments (air and water, at a temperature of 32 degrees C). They were always equipped with electrodes protected with a waterproof adhesive tape. No significant variations (paired Wilcoxon test) due to the environments were observed in the median frequency of the power spectrum (MDF) and in the root mean square (RMS) value of the sEMG signal. These results allow us to assess the methodological criteria to properly record sEMG signals in water and provide the basis to explain different findings obtained by other authors.

Control of respiratory and cardiovascular functions by leptin.

Leptin, a peptide hormone produced by adipose tissue, acts in brain centers that control critical physiological functions such as metabolism, breathing and cardiovascular regulation. The importance of leptin for respiratory control is evident by the fact that leptin deficient mice exhibit impaired ventilatory responses to carbon dioxide (CO2), which can be corrected by intracerebroventricular leptin replacement therapy. Leptin is also recognized as an important link between obesity and hypertension. Humans and animal models lacking either leptin or functional leptin receptors exhibit many characteristics of the metabolic syndrome, including hyperinsulinemia, insulin resistance, hyperglycemia, dyslipidemia and visceral adiposity, but do not exhibit increased sympathetic nerve activity (SNA) and have normal to lower blood pressure (BP) compared to lean controls. Even though previous studies have extensively focused on the brain sites and intracellular signaling pathways involved in leptin effects on food intake and energy balance, the mechanisms that mediate the actions of leptin on breathing and cardiovascular function are only beginning to be elucidated. This mini-review summarizes recent advances on the effects of leptin on cardiovascular and respiratory control with emphasis on the neural control of respiratory function and autonomic activity.

Activation of the brain melanocortin system is required for leptin-induced modulation of chemorespiratory function.

UNLABELLED: Melanocortin receptors (MC3/4R) mediate most of the metabolic and cardiovascular actions of leptin. AIM: Here, we tested if MC4R also contributes to leptin's effects on respiratory function. METHODS: After control measurements, male Holtzman rats received daily microinjections of leptin, SHU9119 (MC3/4R antagonist) or SHU9119 combined with leptin infused into the brain lateral ventricle for 7 days. On the 6th day of treatment, tidal volume (VT ), respiratory frequency (fR ) and pulmonary ventilation (VE ) were measured by whole-body plethysmography during normocapnia or hypercapnia (7% CO2 ). Baseline mean arterial pressure (MAP), heart rate (HR) and metabolic rate were also measured. VE , VT and fR were also measured in mice with leptin receptor deletion in the entire central nervous system (LepR/Nestin-cre) or only in proopiomelanocortin neurones (LepR/POMC-cre) and in MC4R knockout (MC4R(-/-) ) and wild-type mice. RESULTS: Leptin (5 µg day(-1) ) reduced body weight (~17%) and increased ventilatory response to hypercapnia, whereas SHU9119 (0.6 nmol day(-1) ) increased body weight (~18%) and reduced ventilatory responses compared with control-PBS group (Lep: 2119 ± 90 mL min(-1)  kg(-1) and SHU9119: 997 ± 67 mL min(-1)  kg(-1) , vs. PBS: 1379 ± 91 mL min(-1)  kg(-1) ). MAP increased after leptin treatment (130 ± 2 mmHg) compared to PBS (106 ± 3 mmHg) or SHU9119 alone (109 ± 3 mmHg). SHU9119 prevented the effects of leptin on body weight, MAP (102 ± 3 mmHg) and ventilatory response to hypercapnia (1391 ± 137 mL min(-1)  kg(-1) ). The ventilatory response to hypercapnia was attenuated in the LepR/Nestin-cre, LepR/POMC-cre and MC4R(-/-) mice. CONCLUSION: These results suggest that central MC4R mediate the effects of leptin on respiratory response to hypercapnia.

Differential cellular reactivity to adult worm antigens of patients with different clinical forms of schistosomiasis mansoni.

Analysis of the proliferation in vitro of peripheral blood mononuclear cells and the production of interferon-gamma (IFN-gamma) in individuals infected with Schistosoma mansoni and showing different clinical forms of the disease, as well as normal putatively immune individuals from an endemic area, was undertaken using total and fractionated soluble adult worm antigens (SWAP). A higher frequency of detectable response to fractionated antigens in T cell Western blot assays was observed in individuals with the more severe forms of the disease. Analysis of variance showed that, in the Western blot assays, there was a statistically significant difference in the level of cellular proliferation to antigens with low molecular weight (less than 21 kDa) between hepatosplenic patients and those with intestinal and hepatointestinal forms of the disease. No correlation between cellular proliferation and IFN-gamma production was observed. Most of the normal individuals from an endemic area failed to show significant proliferative responses to SWAP T cell Western blot assays or to antigen immobilized on nitrocellulose; they did show significant proliferative responses to whole soluble SWAP with positive IFN-gamma production. The results are consistent with the hypothesis that variations in the cellular immune responses to SWAP influence both the development of pathology and resistance to infection in schistosomiasis mansoni.

Parenteral nutrition and cyclosporine: do lipids make a difference? A prospective randomized crossover trial.

AIMS: This prospective, controlled, randomized crossover trial was conducted to assess the effects of parenteral nutrition, with or without lipids, in cyclosporine (CyA) pharmacokinetics. METHODS: 10 adult patients were randomized on the day of allogeneic bone marrow transplantation to receive isocaloric and isonitrogenous parenteral nutrition admixtures without (regimen A) or with lipids (regimen B). Admixtures were started on average by day + 7.4; 5 patients received regimen A followed by B, 5 in reverse order. Blood samples were collected at day 4 after transplantation, under oral diet, and 4 days after the initiation of each regimen as the sole nutrition support. At each time point, 8 whole blood samples were analysed for CyA to evaluate: area under the curve (AUC), trough concentration and systemic clearance. Clinical/laboratory events were recorded until 31 months of follow-up. RESULTS: There was no evidence of a period or treatment-by period interaction, thus results were combined for further analysis. There were no statistically significant differences between regimens in any CyA pharmacokinetic parameters; there were no significant differences from baseline values, except for a higher systemic clearance of CyA with regimen A (0.40+/-0.09 vs 0.29+/-0.06 L/Kg/h, p=0.03). CONCLUSIONS: The provision of 0.8 g/Kg/d of a 50:50 mixture of medium and long chain triglycerides did not affect CyA parameters, which were closer to baseline. In the short or long term there were no attributable side effects.

Clinical profile of patients with Chagas' disease before and during sustained ventricular tachycardia.

Sustained ventricular tachycardia was diagnosed in 15 patients undergoing ordinary activity with Chagas' disease seen at our Institute from 1978 to 1989. Palpitations were observed in 11 (66%) of the patients, dyspnea in 7 (46%), atypical chest pain in 5 (33%) and syncope in 2 (13%). Cardiac arrhythmia was detected in 4 (26%) on physical examination. The resting electrocardiogram showed premature ventricular contractions in 13 (86%) patients, ST-T changes in 12 (80%), left axis deviation in 9 (60%) and right bundle branch block in 4 (26%). Chest X-rays showed mild cardiomegaly in 8 (53%) and moderate cardiomegaly in 3 (20%) patients. Mild left ventricular dysfunction was detected echocardiographically in 1 (10%), moderate in 3 (30%) and severe in 1 (10%) of the 10 patients studied. During sustained ventricular tachycardia, dyspnea was found in 7 of 15 (46%) patients, palpitations in 6 (40%), atypical chest pain in 6 (40%), syncope in 1 (6%), systemic arterial hypotension in 3 (20%) and cardiogenic shock in 2 (13%). The electrocardiographic findings were as follows: mean heart rate was 201 bpm; mean QRS lengthening was 0.16 sec; right bundle branch block plus right axis deviation was seen in 5 of 15 (33%) patients; right bundle branch block plus left axis deviation in 4 (26%); and a positive concordance of all precordial leads in 5 (33%) patients. Based on these findings, we conclude that the majority of patients with Chagas' disease who develop sustained ventricular tachycardia do not have severe myocardial disease, show an uncommon electrocardiographic pattern of this arrhythmia, and most importantly, have a benign clinical course.

Clinical characteristics of acute myocardial infarction in patients with Chagas' disease.

From 1981 to 1988, 404 patients at our institution were found to have acute myocardial infarction. Of them, 18 (4%) had a positive fixation test for Chagas' disease. Patient age ranged from 41 to 80 years (median = 59). Eleven patients were males. Eighteen nonchagasic patients were matched by 2 year age intervals and sex with each chagasic patient. Before acute myocardial infarction, there were no differences between chagasic and nonchagasic patients with regard to the proportion of stable angina, unstable angina and coronary risk factors. Atypical chest pain occurred in 8 of 15 (53%) chagasic patients for whom this information was found in the medical records and in 1 of 18 (5%) nonchagasic patients (p = 0.003); dyspnea and palpitations occurred in 6 of 15 (40%) chagasic and 1 of 17 (5%) nonchagasic patients (p = 0.025). There were no differences between chagasic and nonchagasic patients with respect to both clinical characteristics and cardiac complications of acute myocardial infarction. Nonetheless, 4 of 11 (36%) chagasic patients for whom this information was listed in the medical records but none of 16 nonchagasic patients had normal coronary arteries (p = 0.019). Thus, chagasic patients who develop acute myocardial infarction have some peculiarities both in the clinical profile before the acute event and in the anatomy of the coronary arteries.

[Action-oriented information systems: subsidies for activities by workers' health programs at the local level]. / Sistema de informação para a ação: subsídios para a atuação prática dos programas de saúde dos trabalhadores a nível local.

Over the course of recent decades, Brazil has become an industrialized society. From an epidemiological perspective and considering changes that have been occurring in the Brazilian population, particularly concerning demographic and epidemiological transitions, this paper discusses the need to adapt the epidemiological surveillance system in order to incorporate the surveillance of non-transmissible diseases. The authors analyze the information system for work-related accidents in the Workers' Health Program, under SUDS (the Unified Decentralized Health System) for the Mandaqui Region (in the Northern part of the city of São Paulo), based on data from a local metalworking industry identified by the information system as a high-risk site for work-related accidents. The article also focuses on the importance of organized workers participating in actions to control work-related accidents. Although such participation is not always possible, the health sector must incorporate the workers' own concrete experience in order to develop more effective actions to prevent accidents at the workplace.

[Epidemiological surveillance system for occupational accidents: experience in the northern area of the municipality of São Paulo (Brazil)]. / Sistema de vigilância epidemiológica para acidentes do trabalho: experiência na zona norte do município de São Paulo (Brasil).

The epidemiological approach to occupational accidents and diseases adopted in Brazil is inadequate for many reasons, among them being: 1) the fact that only employers may notify work accidents, thus permitting notorious undernotification of these occupational hazards; 2) the available information does not permit a better understanding of the causal relationship between work accidents and diseases; 3) the official policy exists only for purposes of insurance compensation. The official documents for occupational disease and accident registration are the CTA (Work accident report) and FTA (Casualty treatment card). The Worker's Health Program of SUDS-R-6 proposed, in October, 1988 a method for the codification, registration in a micro-computer data bank and analysis of this information, based on the records presently in use (CAT) for public health service planning and accident prevention purposes. The major interest was in identifying the most common types of accidents in the region and the work environments in which they most frequently occur. The target population were the workers who attended the health units lisenced to deal with work accidents and diseases, in the Northern region of S. Paulo City. The data presented below refer to the months of October, November and December, 1988, the first three months of the project. During that period a total of 2,339 accidents were registered. They were classified as: typical work accidents - 87%: commuting accidents which occurred between the home and the work-place--18% and work diseases (only 2 cases). The majority of workers (50%) were between 25 and 45 years of age, approximately 7% were under 18. Male workers represented 83.2% of accident cases.(ABSTRACT TRUNCATED AT 250 WORDS)

[Unusual form of presentation of acute monocytic leukemia. Report of a clinical case that developed endocarditis]. / Forma pouco habitual de apresentação de leucemia monocítica aguda. A propósito de um caso clínico que evoluiu com endocardite.

The authors describe an acute monocytic leukemia (M5) developed in a 16-year-old boy with febril syndrome, aortic valve vegetations, bicytopenia and dismyelopoieses.

[Acute promyelocytic leukemia. The therapeutic advances]. / Leucemia promielocítica aguda. Avanços terapêuticos.

Acute promyelocytic leukemia (APL) is a rare subtype of acute myelogenous leukemia. It is frequently associated with a life-threatening hemorrhagic diathesis, often aggravated by induction cytotoxic chemotherapy. Patients with APL have bone marrow infiltration by abnormal promyelocytes, usually with prominent cytoplasmic granulation. These patients have a unique cytogenetic abnormality, a balanced reciprocal translocation between the long arms of chromosomes 15 and 17. The nuclear retinoic acid receptor alpha gene, on chromosome 17, is translocated to the PML gene region, on chromosome 15, resulting in the synthesis of two fusion messenger ribonucleic acids, PML/RAR-alpha and RAR-alpha/PML, easily detected by the reverse transcriptase polymerase chain reaction. This assay is extremely useful in the diagnosis and detection of minimal residual disease in APL patients. All trans-retinoic acid (ATR) differentiates the malignant cell clone and corrects the coagulopathy associated with this disease. The most important adverse effect is a respiratory distress syndrome, treatable with steroids, if detected at its onset. ATR yields durable remissions in patients with APL, after consolidation with cytotoxic chemotherapy.

[Treatment of acute promyelocytic leukemia with trans-retinoic acid. Experience of the Santa Maria Hospital, Medical School of Lisbon]. / Terapêutica da Leucemia promielocítica aguda com ácido Trans-Retinóico. Experiência do Hospital de Santa Maria, Faculdade de Medicina de Lisboa.

Acute promyelocytic leukemia (APL) is a rare subtype of acute myelogenous leukemia that is usually associated with a fatal hemorrhagic diathesis. All trans-retinoic acid (ATRA) is an active metabolite of vitamin A that differentiates the malignant cell clone, corrects the coagulopathy, and induces complete remission in the vast majority of patients with APL. Between June 1992 and September 1993, 8 patients with APL (4 previously untreated, 3 in first relapse and 1 in second relapse) received ATRA. Complete remission was achieved in 7 patients; in 5 with ATRA alone and in 2 with ATRA followed by cytotoxic chemotherapy due to the development of asymptomatic hyperleukocytosis. The earliest signs of response were the correction of the coagulopathy and an increase in the white blood cell count. Sequential morphological and immunophenotypical analyses of the bone marrow revealed differentiation of the malignant cell clone, in the absence of bone marrow hypoplasia. 4 of 5 patients treated only with ATRA until complete remission had late leukopenia. The most frequent adverse effects were dryness of skin and mucosae, hypertrigliceridemia and hypercholesterolemia, and a moderate increase in liver transaminases. An increase in the white blood cell count was common, and in two cases exceeded 35.0 x 10(9)/l. One of these patients developed multiple thrombosis of the extremities after cytotoxic chemotherapy. We frequently observed an increase in lactic dehydrogenase levels that was concomitant with the peak in the white blood cell count. The only patient on whom complete remission was not achieved was 60 years old, had chronic obstructive pulmonary disease, and died in the third week of therapy with a pulmonary distress syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)