Waldenström macroglobulinaemia: presenting features and outcome in a series with 217 cases.

In this report we analyse the presenting features of a series of patients diagnosed with Waldenström macroglobulinaemia (WM) in Spain over the last 10 years. Criteria for diagnosis required a serum monoclonal IgM protein > or = 30 g/l and > 20% bone marrow lymphocytes. Two hundred and seventeen patients were included in the study, with a median age of 69 years and male/female ratio of 2:1. The most common symptoms at diagnosis were anaemia (38%), hyperviscosity (31%), B symptoms (23%), bleeding (23%) and neurological symptoms (22%). Sixty-one patients (27%) were asymptomatic at diagnosis and, to date, 32 of them have not received chemotherapy. Variables predicting a shorter survival free of therapy were haemoglobin < 12.5 g/dl and high beta2microglobulin (beta2M). The 83% of patients who did receive treatment were distributed as follows: chlorambucil/prednisone (43%), intermittent chlorambucil (11%), continuous chlorambucil (26%), cyclophosphamide/vincristine/prednisone (COP, 13.5%) and other (6.5%). Response to therapy was complete in 2%, partial in 48% and minor in 10%. Finally, 28% and 13% of patients presented stable and progressive disease, respectively, which was more common among patients treated with COP. Progression-free survival was 43% at 5 years, with three independent predictors for shorter progression-free survival (PFS): COP treatment, age > 65 and B symptoms at diagnosis. The 10-year projected overall survival (OS) was 55%. The two most frequent causes of death were development of second malignancies (31%), or infections (19%). The two main variables predicting a poor OS were hyperviscosity and high beta2M. In summary, this study favours the use of chlorambucil-based therapy as the standard treatment for WM, and describes a subset of patients who should be considered as suffering a smouldering form and who therefore do not require treatment for a long period of time.

[Regulation of cardiac output;an approximation at 3 levels: organic, cellular, and protein]. / Regulación del rendimiento cardíaco; una aproximación a tres niveles: órgano, células, proteínas.

The heart is the central point for adaptation of the organism to physical exercise because it is the center of the energy support system. Its activity is regulated at three levels; organ, cells and molecular and genetic components. During the development of the heart, the organ adapts in response to chronic and acute overloads by instantaneous functional and chronic changes, leading to a variable degree of cardiac growth. Physical exercise (acute and chronic) is the main example of physiologic overload. The acute response of the heart means a mechanical-hemodynamical and energetic modulation, driving to a final point where oxygen supply fits the increased need. Training, as response to chronic exercise, promotes an increase in energetic capacity (heart rate and stroke volume), structurally reflected in the physiological cardiac hypertrophy. Global functional and structural changes express what is happening at the cellular level. Different stimuli signal through specific receptors and second messengers to the nucleus, regulating gene expression and conditioning structural (size) and functional (contractile) changes. Changes in cellular size explain, by Starling mechanism, the increase in individual contractile strength and in reduction of the ventricular cavity in the systolic period. Other structural changes refer to the interstitium, myocardial vasculature and vascular reactivity. Changes in contractility affect the composition of the contractile elements (isoforms of heavy myosin, light myosin and/or modulatory proteins) and sarcoplasmic Ca2+ regulation, through the increase in Ca2+ flow. Many of the adaptations to chronic exercise studied in vivo in intact heart, isolated heart (Langendorf) or papillary muscle (multicellular preparation), are retained in the cardiomyocyte. Isolated cardiomyocytes can be precisely through the medium, temperature, ionic composition, active substances, etc. Shortening speed without load (Vmax), considered an inotropic index (Sonnenblick) can be measured independently of the initial length. Myocytes shorten against an internal load (restoration force) with viscous and elastic components, although they cannot be loaded externally (stretching is difficult). Cardiomyocyte isolation and maintenance requires strict and controlled conditions. This model offers many possibilities for studying dimensions, contraction-relaxation mechanics, Ca2+ and pH dynamics, beta-adrenergic receptors, electrophysiology, pharmacology, genetics, etc. This kind of studies can deal with normal myocytes or myocytes from trained animals, cardiomyopathies, etc.

[Simplified Ramírez urethropexy in the treatment of genuine stress urinary incontinence in women. Multicenter study of clinical and urodynamic results]. / Uretropexia simplificada de Ramírez en el tratamiento de la incontinencia urinaria de esfuerzo genuina en la mujer. Estudio multicéntrico sobre los resultados clínicos y urodinámicos.

OBJECTIVES: To evaluate the clinical and urodynamic data of a multicenter study on female urinary stress incontinence undergoing surgical repair with the Ramírez simplified urethropexy. METHODS: Clinical, urodynamic and videocystographic data were analyzed in a multicenter series of 340 female patients with urinary stress incontinence (mean age 51.7 +/- 9.7 years) before and after the Ramírez urethropexy technique (mean follow-up 21.7 months). RESULTS: Post surgical urinary continence was 78.4%. Cystocele repair was demonstrated in 57.7%. Urge incontinence decreased in 17.1%. Daytime frequency statistically significantly decreased in 19%. Urinary obstructive symptoms increased in 19.3%. Bladder instability significantly decreased posturethropexy. Peak urinary flow rate and mean urinary flow rate diminished in 65% and 59%, respectively. Postvoiding residual urine increased significantly. No statistical correlation between posturethropexy continence and videocystographic bladder neck morphology was observed. CONCLUSIONS: The clinical and urodynamic data obtained in our series indicate that the Ramírez urethropexy technique, a simple and fast procedure, may be considered an alternative treatment in female urinary stress incontinence.