Objectivism

Reason (the faculty which identifies and integrates the material provided by man’s senses) is man’s only means of perceiving reality, his only source of knowledge, his only guide to action, and his basic means of survival.

Is this knowledge in the practical sense or the philosophical one? I'm very doubtful about the 100% certainty, 100% correctness sort of knowledge. Seems to me also that someone with zero reason can perceive reality, just not understand it. But hey! We can't understand reality either. 

Man—every man—is an end in himself, not the means to the ends of others. He must exist for his own sake, neither sacrificing himself to others nor sacrificing others to himself. The pursuit of his own rational self-interest and of his own happiness is the highest moral purpose of his life.

If I am, say, a psychopath and a serial killer, and my work fills me with the greatest of happiness,  then acting in my own rational self-interest would result in sacrificing lots of people to myself. A normal person, of course, would not be serving their own interests by going on a murderous rampage, even if they could get away with it. But does Objectivism imply that this psychopath has a duty to others (albeit an effortless one) not to kill them, even though it conflicts with his rational self-interest?

As for "man must exist for his own sake", I think it's up to him what he exists for. Though maybe that's what Rand meant

I am indeed very doubtful about selflessness. I don't think it's possible to truly put the interests of others above your own. Implied in any  of your conscious actions is that you wanted to do them. You may wish you could do an infinite number of other things, but ultimately you have chosen what you identify as the best option. In this sense of the word "want", doing something you don't want to do is absurd.

If we are talking about "selflessness" as seen in pulling a stranger's children out of a house on fire...

I think it's clear that the hero of the story gets emotional benefit out of saving lives. This is due to the natural and perfectly healthy sense of empathy, which has evolved in humans an other social animals. Rescuing the children feels good in a very profound way. Perhaps more importantly, not rescuing the children could result in crippling guilt for the average human being, who does not like seeing others suffer. Self-interest, in my opinion, is much more charitable and caring than people make it out to be.

If you find I am making no sense, feel free to watch this clip from Friends. I'm on Joey's side in this matter. Phoebe is a wonderful and generous person, but that doesn't mean she isn't selfish, and that doesn't mean selfishness is bad.