Objectives To determine the efficacy of a three-fold reduced dose (RD, 27 mg) of intravesical bacille CalmetteGuérin (BCG) against the standard dose (81 mg) in patients with superficial bladder cancer, assessing recurrence, progression and differences in toxicity. Patients and methods Five hundred patients with superficial bladder cancer (Ta, T1, Tis) were enrolled and randomly assigned to be treated after transurethral resection of all visible lesions with intravesical BCG Connaught strain (weeklyrsix and thereafter fortnightlyrsix) either with the standard or RD instillation. Results All but one of the 500 patients were evaluable for efficacy and toxicity (252 in the standard arm and 247 in the RD arm). The median follow-up was 69 months (maximum 104); 71 (28%) patients in the standard arm and 76 (31%) in the RD arm developed recurrences; the median time to recurrence has not yet been attained, but at 5 years the mean (SD) percentage of recurrence-free patients was 70.5 (3.12) and 70.4 (3.1) for the standard and RD arms, respectively. In patients presenting with multifocal tumours, the standard dose was more effective against recurrences than the RD (P=0.0151). In those with G3 and high-risk tumours overall, the superiority of the standard dose was marginal (P=0.060 and P=0.082). Twenty-nine (11.5%) tumours in the standard arm and 33 (13.3%) in the RD arm progressed to invasive disease; the median time to progression has not yet been attained, but the percentage of progression-free patients at 5 years was 88.8 (2.23) and 86.9 (2.31) for the standard and RD arms, respectively. The standard dose was more effective than the RD against progression only in patients with multifocal disease (P=0.048). Twelve (4.8%) cystectomies were performed in the standard and 15 (6.1%) in the RD arm. Currently, 106 (21.2%) patients have died, but only 38 (7.6%) from bladder cancer, i.e. 20 (7.9%) in the standard and 18 (7.5%) in RD arm. Overall the disease-specific death rate was lower for those patients who completed the scheduled treatment. The cause-specific survival at 5 years did not differ between the arms (P=0.76) but there was a trend toward better cause-specific survival for patients with multifocal tumours in the standard arm. Toxicity differed between the arms, significantly more patients having no toxicity in the RD arm, and fewer having delayed instillations or withdrawing. However, severe systemic toxicity occurred even in patients treated with the RD, in a similar proportion to those receiving the standard dose. Conclusion Overall, the RD gave similar results for recurrence and progression but with significantly less toxicity. However, patients with multifocal tumours fared better with the standard dose and there was a trend towards better recurrence rates in patients with highrisk tumours. We recommend continuing to use the standard dose for high-risk tumours, while we consider the reduced dose safe and effective for intermediaterisk lesions and for maintenance schedules.
The physiological mechanisms, behavioral adjustments, and ecological associations that allow animal species to live in extreme environments have evoked the attention of many zoologists. Often, extreme environments are defined as those believed to be limiting to life in terms of water, energetic availability, and temperature. These three elements seem extreme in a number of arid and semi-arid settings that even so have been colonized by amphibians. Because this taxon is usually seen as the quintessential water-dependent ectotherm tetrapods, their presence in a number of semi-arid environments poses a number of intriguing questions regarding microhabitat choice and physiological plasticity, particularly regarding the ecological and physiological correlates of behaviors granting avoidance of the harshest conditions of semi-arid environments. Such avoidance states, generally associated to the concept of aestivation, are currently seen as a diverse and complex phenomena varying from species to species and involving numerous behavioral and metabolic adjustments that enhance survival during the drought. This chapter reviews the physiological ecology of anuran aestivation, mainly from the perspective of water and energy balance.
Aim To compare morphometric data of the eyelid fissure and the levator muscle function (LF) before and up to 6 months after transcutaneous injection with five units of Botox s in patients with upper lid retraction (ULR) from congestive or fibrotic thyroid eye disease (TED). Methods Twenty-four patients with ULR from TED were submitted to transcutaneous injection of 5 units (0.1 ml) of Botox in one eye only. Patients were divided into two groups: 12 with congestive-stage TED (CG), and 12 with fibrotic-stage TED (FG). Bilateral lid fissure measurements using digital imaging and computer-aided analysis were taken at baseline and at regular intervals 2 weeks, 1 month, 3 months and 6 months after unilateral Botox injection. Mean values taken at different follow-up points were compared for the two groups. Results Most patients experienced marked improvement in ULR, with a mean reduction of 3.81 mm in FG and 3.05 mm in CG. The upper eyelid margin reflex distance, fissure height and total area of exposed interpalpebral fissure were significantly smaller during 1 month in CG and during 3 months in FG. Reduction in LF and in the difference between lateral and medial lid fissure measurements was observed in both groups. The treatment lasted significantly longer in FG than in CG.Conclusions A single 5-unit Botox injection improved ULR, reduced LF and produced an adequate lid contour in patients with congestive or fibrotic TED. The effect lasts longer in patients with fibrotic orbitopathy than in patients with congestive orbitopathy.
INTRODUÇÃOA Unidade de Terapia Intensiva (UTI) tem sido caracterizada como um ambiente complexo, decorrente do uso crescente da tecnologia que visa atender melhor o paciente. O tratamento implantado nesse ambiente é considerado agressivo e invasivo, traduzindo-se poruma alta intensidade e complexidade de eventos e situações. Outra característica desta unidade é a despersonalização do ser, pois o paciente encontra-se fora do seu ambiente familiar, social e profissional para ficar em um ambiente desconhecido. 6 . * * E n f e r m e i r a , p r o f a. d o D e p t o d e E n f e r m a g e m -F C M -U N I C A M P . D o u t o r a n d a n a A r e a d e E n f e r m a g e m F u n d a m e n t a l p e l a E s c o l a d e E n f e r m a g e m e R i b e i r ã o P r e t o -U S P .
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