Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium.

BACKGROUND: Advanced-stage mycosis fungoides (MF)/Sézary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. PATIENTS AND METHODS: This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). RESULTS: Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. CONCLUSION: This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach.

Platelet-activating factor (PAF) induces wheal and flare skin reactions independent of mast cell degranulation.

BACKGROUND: Platelet-activating factor (PAF) causes wheal and flare responses which are abrogated by H1-antihistamines giving rise to the hypothesis that PAF-induced wheal development is secondary to histamine release from dermal mast cells. But is this hypothesis correct? METHODS: Wheal and flare responses were induced by intradermal injection of PAF, codeine and histamine in 14 healthy volunteers. Dermal histamine and PGD2 contractions were measured using microdialysis. RESULTS: PAF, unlike histamine and codeine, did not cause a statistically significant rise in mean histamine levels with ten persons showing negligible histamine release. Codeine caused a significant but variable histamine release, ranging from 29 to 282 ng/ml. Codeine, but not PAF or histamine, caused a small but statistically significant release of PGD2. CONCLUSION: Wheal and flare reactions in human skin induced by PAF are not associated with histamine release and, therefore, appear to be independent of mast cell degranulation.

Effects of propranolol and timolol on left ventricular volumes during exercise in patients with coronary artery disease.

The hemodynamic effects of beta-receptor blocking agents on the ejection fraction of patients with coronary artery disease during exercise have been studied previously using radionuclide techniques. Left ventricular volume measurements and the peak systolic pressure/end-systolic volume (PSP/ESV) index have been shown to be variables of left ventricular function that are less influenced by preload and afterload than is ejection fraction. Left ventricular volumes and PSP/ESV were therefore measured in 18 patients with proven coronary artery disease in the control state and after 2 weeks of daily maintenance therapy with either 240 mg propranolol or 60 mg timolol. Values at rest and during symptom-limited upright exercise were compared using the first pass technique and a multicrystal scintillation camera. Left ventricular volumes were measured by the area-length method. Because there was no difference between the propranolol and timolol groups, the results for both groups were combined. The ejection fraction at rest after beta-receptor blocker treatment was not significantly different from pretreatment measurements because of an increase in both end-diastolic and end-systolic volumes (p less than 0.01). However, the value for peak systolic pressure/end-systolic volume (PSP/ESV) index at rest was lower after treatment. The exercise ejection fraction was greater after treatment (p less than 0.01), owing to an increase in end-diastolic volume and unchanged end-systolic volume. In addition, there was a significant improvement in the directional change in the PSP/ESV ratio between rest and exercise from pretreatment to treatment (-1.1 +/- 2.5 to +0.2 +/- 1.2, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Improved exercise ejection fraction with long-term prazosin therapy in patients with heart failure.

To study the effect of prazosin therapy on left ventricular function in patients with chronic stable heart failure, first pass radionuclide angiography at rest and during exercise was performed in 15 patients before the administration of prazosin and after seven to 12 weeks of prazosin therapy. There was no significant change in resting ejection fraction before and during prazosin therapy (36 +/- 14 per cent versus 37 +/- 14 per cent) (mean +/- standard deviation). However, exercise ejection fraction increased from 34 +/- 14 per cent to 42 +/- 17 per cent (p less than 0.01). The difference in ejection fraction from rest to exercise (ejection fraction response) changed significantly from -2 +/- 6 per cent before prazosin therapy to +5 +/- 7 per cent during prazosin therapy (p less than 0.01). Exercise duration increased from 368 +/- 82 seconds to 476 +/- 82 seconds (p less than 0.01). Total work capacity measured in kilojoules increased from 12.6 +/- 8.3 to 18.6 +/- 10.4 (p less than 0.01). The improved ejection fraction response during prazosin therapy correlated with the improved work capacity (r = 0.69, p less than 0.01) and exercise duration (p = 0.59, p less than 0.05). This improvement occurred despite a significant weight gain with prazosin from 72.2 +/- 20.8 kg to 73.5 +/- 20.8 kg (p less than 0.01). These data suggest that long-term prazosin therapy is effective in the treatment of heart failure. However, the beneficial effects of prazosin, an alpha 1 blocking agent, may be evident only during exercise.

Hemodynamic effects of labetalol in patients with combined hypertension and left ventricular failure.

To investigate the safety of labetalol in the treatment of hypertension in patients with heart failure, sixteen hypertensive patients with a history of congestive heart failure and an ejection fraction at rest less than 45%, had measurements of ejection fraction and cardiac output by first pass radionuclide angiography at baseline, at the end of 2 weeks maintenance with labetalol (titrated to the effective antihypertensive dose of 200-1600 mg daily), and in the post-treatment placebo period. On labetalol, heart rate and blood pressure were significantly lower than placebo at rest and the ejection fraction was higher (30 vs 25%) (p less than 0.05). At maximal exercise on labetalol the heart rate and blood pressure were lower than at placebo maximal exercise (p less than 0.05) and the ejection fraction was higher (32 vs 27%) (p less than 0.01). Exercise tolerance was not changed by labetalol. No patient was discontinued from the study because of worsening heart failure. Dizziness was reported in 5 of 16 patients usually at one visit. Dyspnea that was reported in 4 of 16 patients improved with minor adjustments in digitalis or diuretic dose. In conclusion, labetalol reduces blood pressure in hypertensive patients with left ventricular dysfunction without reducing cardiac performance.

The effect of captopril on renal, coronary, and systemic hemodynamics in patients with severe congestive heart failure.

The effects of captopril (CPT), an oral angiotensin-converting enzyme (ACE) inhibitor, on systemic failure (CHF). In 15 patients, CPT decreased mean arterial pressure from 75 +/- 3 to 60 +/- 3 mm Hg associated with a 16% increase in cardiac output, a 24% reduction in systemic vascular resistance, and a 36% decrease in pulmonary capillary wedge pressure (all p less than 0.01). Despite the improved cardiac output, renal blood flow, creatinine clearance, and sodium excretion did not rise during the first 2 days of CPT therapy. In eight patients, coronary sinus blood flow diminished from 98 +/- 11 to 82 +/- 9 ml/min (p less than 0.01) following drug administration in association with a fall in arterial pressure and heart rate but no change in coronary sinus oxygen inhibitor failed to improve renal hemodynamics. In addition, initial CPT administration produced a decrease in coronary blood flow that was related to a decrease in myocardial oxygen requirements.

Orquidopexia laparoscópica en el testículo intraabdominal del niño / Laparoscopic orchidopexy in intraabdominal testis in child

La laparoscopía es el método diagnóstico de elección para la localización del testículo no palpable del niño. Hemos empleado este procedimiento en 21 niños con una correlación de 100 por ciento con los hallazgos de la exploración quirúrgica. En 2 niños encontramos 4 testículos intraabdominales, realizando en ambos un clipaje laparoscópico de los vasos espermáticos. Entre 4 y 7 meses después se efectuó nueva exploración laparoscópica con sección de los vasos espermáticos y realizando una orquidopexia bilateral asistida por laparoscopía. En el niño con testículo no palpable, la laparoscopía constituye un método tanto diagnóstico como terapéutico