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* Romney wins in Wisconsin, Maryland, Washington, D.C.

* He strengthens grip on Republican U.S. presidential race

* Sweep increases pressure on rival Santorum to quit race

* Obama jumps into the fight

(Adds analyst comment)

By Steve Holland

MILWAUKEE, April 3 (Reuters) – Mitt Romney made a big leap

toward winning the Republican U.S. presidential nomination with

a clean sweep of three primaries on Tuesday that handed a

stinging defeat to chief rival Rick Santorum.

The victories in Wisconsin, Maryland and Washington, D.C.

will increase appeals from Republican party leaders for Santorum

to quit so that Romney can gird for a difficult fight against

President Barack Obama in the Nov. 6 election.

In his victory speech in Milwaukee, Romney ignored Santorum

and gave voters a sense of what the general election campaign

will be like, sharply criticizing Obama for his handling of the

U.S. economy and high gasoline prices.

“It’s enough to make you think that years of flying around

on Air Force One, surrounded by an adoring staff of true

believers telling you what a great job you are doing, well, that

might be enough to make you a little out of touch,” Romney said.

In a clear sign that Obama sees Romney as his chief obstacle

to re-election, the president singled him out by name and

criticized him in a speech with a sharp partisan tone on

Tuesday.

The trio of defeats puts conservative Santorum’s campaign in

serious trouble. He is badly trailing Romney in both delegates

and fundraising.

“I think it’s lights out for Santorum,” said Republican

strategist Ron Bonjean. “He can run a sideshow campaign for the

next couple of months, but the spotlight is shining on Romney.”

Santorum, a former Senator, vowed to stay in the race at

least until April 24 when his home state of Pennsylvania votes

and where he is hanging on to a lead in the polls over Romney.

PENNSYLVANIA KNOCKOUT?

That date looms as a potentially decisive one, with Romney

likely to win five states that hold contests then and planning a

big challenge to Santorum in Pennsylvania.

Tuesday’s victories widened Romney’s lead over Santorum in

delegates to an estimated 640-264, according to CNN. Romney now

has more than half of the 1,144 delegates he needs to clinch the

nomination at the Republican convention in August.

Santorum wants to win enough delegates to deny his opponent

an outright victory before the convention in Tampa.

“Who’s ready to charge out of the locker room in

Pennsylvania for a strong second half?” Santorum said to cheers

in a speech after Tuesday’s result. “This isn’t half time. We’re

hitting the field. The clock starts tonight.”

“We don’t win by moving to the middle. We win by getting

people in the middle to move to us and move this country

forward,” Santorum said.

A Quinnipiac University poll showed Santorum ahead of Romney

in Pennsylvania by 41 to 35 percent, but the former private

equity executive’s campaign and its allies are likely to spend

big on negative ads against Santorum in the coming weeks.

Obama hit out at Romney on Tuesday for backing a

controversial Republican budget plan authored by a key Wisconsin

backer of Romney, Congressman Paul Ryan.

“He said that he’s very supportive of this new budget and he

even called it ‘marvelous,’ which is a word you don’t often hear

when it comes to describing a budget,” Obama said in a speech.

Romney fired back that Obama was trying to deflect blame for

high gasoline prices that are hitting American wallets hard and

could make Obama’s re-election tougher to achieve.

“So the president put an ad out yesterday, talking about

gasoline prices and how high they are. And guess who he blamed?

Me!” Romney said in Waukesha, Wisconsin.

“Maybe after I’m president I can take responsibility for

things I might have done wrong. But this president doesn’t want

to take responsibility for his mistakes.”

(Additional reporting by Jeff Mason, Sam Youngman, Deborah

Charles and Lily Kuo; Editing by Alistair Bell and David

Brunnstrom)