Well, I don't know, I tend to think of medicine more as an applied science. It may not meet the definition of pure science, but it still does rely on advances in the pure sciences, it utilizes rational principles and logic, and there are a lot things about it that are reproducible and verifiable. Sure, it suffers from the interference of special interest groups that have other agenda, but I think it's still a far cry from completely non-scientific. And what science is free from such interference anyway?
One of the huge problems is that there are experiments that are doable that will never get funded, especially since there are various industries that have a vested interest in never discovering the answers to certain questions.
There is an enormous difference between the science of medicine and clinical practice.
The science of medicine—the science that figures out pathophysiology, that can determine which genes cause what diseases, what neuronal pathways cause what symptoms, what pharmaceutical agents cause what effects—this is regular science that follows the scientific method and is subject to peer-review.
What doctors do in the office, in the emergency room, and in the hospital are several steps removed from this. To use analogies to other fields, the science of medicine is to clinical practice as, say, what classical physics and materials science is to construction, what the science of semiconductors and electromagnetism is to computer manufacturing, or even what mathematics is to software development.
Clearly you cannot practice clinically without the basis of science, but it's not like you have to run randomized, controlled trials on your patients before you can treat any of them, any more than you need to design an experiment to calculate the value of G in order to build a skyscraper, or design a compiler before you can write a web app.
Clinical medicine is probably more about pattern recognition and the ability to estimate probability and apply Bayes' theorem even when you're missing key pieces of data (not to mention that its also more about empathy, compassion, and striving to make other people's lives better) This is where gut feelings sometimes come in, but still, treatment is generally based on rational principles, and perhaps just as important (at least in the modern era), the patient's informed consent. But science marches on, and doctors will always find that some of what they do is actually completely wrong.
The insurmountable issue is one of ethics. There are a lot of things that we will never be able to test simply because it would be unethical to do those experiments. So we're left with (in some cases) relying on the wisdom of experience, or with extrapolating principles that we can test, and sometimes just outright guessing (although always on the basis of the modern understanding of the processes occurring in the human body.) While doctors will sometimes miss the ruptured appendix, or the silent heart attack, you'll notice that they no longer subscribe to the idea of the four humors, of curing infectious disease by phlebotomizing patients, or treating asthma with urine injections.
The problem was that there were a ton of good, huge studies (still to be refuted) that show that serum cholesterol levels are good measures of predicting coronary artery disease.
What happened was that people assumed that it was simply a matter of diet. If you ate too much fat, your cholesterol levels would shoot through the roof, and you'd be more likely to get a heart attack.
What we are learning is that, while lower serum cholesterol does indeed seem to decrease your risk of rupturing that plaque in your coronaries (much to the joy of the pharmaceutical companies that make HMG-CoA reductase inhibitors), the hypothesis that eating tons of fat causes high cholesterol is not exactly bulletproof. There are obviously lots of other factors in play.
Still, I'm pretty loath to recommend a diet of, for example, nothing but bacon. I'm still pretty sure that eating bacon for breakfast, lunch, and dinner, 7 days a week, will most likely shorten your life.
I think one of the problems is that medical school curricula typically ignore the entire field of nutrition. Sure, they teach the biochemical reactions in which fats, proteins, and carbs are involved, but with regards to how this knowledge might actually be used to help patients, there is often a vast silence.
Add to this the fact that, in general, the medical establishment is extraordinarily conservative, and you end up with clinical practice that lags behind the basic science, and didactics that lag even farther behind clinical practice. So what you learn in med school is like 10 years behind what people actually do in clinical practice (although you may actually get pretty decent basic science if your school happens to have a lot of NIH grants, but, again, this is pretty useless if you actually intend to use this knowledge to treat people) and most clinicians tend to wait 10 years before they start believing anything that basic science and evidence-based medicine tells them (and that's if they even bother to read the big journals.)
Sure, digestion is a complex process and, yes, the laws of thermodynamics don't explain the intricacies of why people get fat and stay fat, but if you search PubMed on obesity, the uniform opinion is that, regardless of what kind of diet you eat, consuming more (kilo)calories than you use will cause you to get fat. This surely is not where the controversy is.
And in particular contexts (specifically illness, extreme stress, and starvation, sometimes also known as dieting), the body does use fat, carbs, and proteins equivalently: they will generally all get broken down in order to replenish the body's store of adenosine triphosphate (ATP), which is the body's true currency of energy, and the amount of ATP generated is proportionate to the amount of energy released by the breakdown of these substances into carbon dioxide, water, and (in the case of proteins), urea. Whatever doesn't get used to make ATP essentially gets shunted into the production of fat.
The big unknown is really how much of what you eat actually makes it into the bloodstream. Some of the variables of interest include intestinal transit time (high carb foods tend to pass through the GI tract faster than fatty and/or proteinaceous foods), time of transport across the intestinal lining (the breakdown products of carbs and proteins are generally more easily absorbed than fat, although not all fat is created equal), the exact composition of your intestinal flora (since the various organisms that live in your gut create all sorts of breakdown products, some of which can get reabsorbed and still used by your body), and the amount of enterohepatic circulation (even if the liver didn't catch it the first time around, it can still get reabsorbed farther down the tract and still actually get used), to name a few.
But what this really boils down to is the fact that the ideal 2,000 (kilo)calorie per day diet is just as fictional as the ideal 70 kg man, and has no specific bearing on whether a pound of potatoes will make you fatter than a 16 oz sirloin. Each of us has an individual energy set-point where usage and consumption are at equilibrium. Running this budget in the red makes us lose weight. Running this budget in the black makes us get fat. The problem is that we don't have a good way of figuring out where this set-point is, and even if we did, the body will always try its damndest to make you break even.
Actually, it's more likely that these bacteria have been exchanging plasmids rather than getting indepedently infected by bacteriophages, but it amounts to the same thing.
All forms of Staph aureus carry the toxin you mention, though, so there's really nothing to prevent you from getting MSSA necrotizing fasciitis.
And, yes, you pretty much need an intact immune system to successfully fight off infection. We can pump you full of every antibiotic known to man and cause every single bacteria in your system to explode, but without neutrophils and macrophages to clean up the resultant toxic mess, you're likely to eventually go into septic shock, which frequently means an eventual trip to the morgue.
Interestingly (most likely due simply to the laws of thermodynamics), it seems that antibiotics-resistant strains are actually less virulent than their non-resistant brethren. The theory is that it takes extra energy to replicate the genes that confer resistance, so these organisms tend not to replicate as quickly. So I find it no accident that most cases of "flesh-eating bacteria" (necrotizing fasciitis) that I've seen are actually caused by MSSA (methicillin-sensitive Staph aureus), although it may simply be that MSSA far outnumbers the amount of MRSA floating around in the environment, and likely MRSA can probably do the same thing. Still, I find that most patients with VRE (vancomycin-resistant enterococcus) aren't necessarily any sicker than patients with vanc sensitive enterococcus.
Nonetheless, I think it demonstrates the importance of keeping your normal flora intact, and that means not demanding antibiotics when you don't need them.
As long as vancomycin can keep Staph aureus at bay, and as long as linezolid (which is available as a pill, and as such, is unfortunately being given out like candy) and dalfopristin/quinupristin (which is hardly ever used except in the sickest of patients and which is only available as IV) can keep VRE in check, we're actually in pretty good shape when it comes to Gram positive cocci. And this may last at least until the decade is out as long as we remain judicious with antibiotic use.
The bacterial pathogens that tend to be more virulent and cause us the most grief in the hospital are Gram negative rods such as E. coli, Pseudomonas, Actinobacter, and Stenotrophomonas, but I think a lot of this lies in the fact that we really haven't had any new drug classes that target GNRs in a really long time. Our drugs of last resort for these puppies are the carbapenems (imipenem, meropenem) and these are basically still based on the same mechanism as penicillin is, except they're more resistant to enzymatic degradation. I know there are new macrolides like telithromycin that are supposed to be better at taking care of GNRs, but macrolides are ridiculously easy for bacteria to figure out, and there is some theoretical concern that macrolide resistance can also confer resistance against our best anti-Gram postive cocci drugs (as above, linezolid and dalfopristin/quinupristin)
So if you want a Nobel Prize, get cracking on some new anti-Gram negative rod antibiotics.
The thing is, most of us do harbor extremely resistant organisms in our gut and on our skin. For one thing, community-acquired MRSA has a prevalence of upwards of 30% in some communities. But most of us are loaded with things like Actinobacter and Stenotrophomonas which usually aren't bad actors until we get pumped full of antibiotics that wipe out the rest of our normal flora that keep them in check, so that these multi-drug resistant organisms are all that are left floating around in our bloodstream, free to frolic and play.
Because hospitals are nothing but incubators for antibiotic resistance, physicians actually do their best to try to get their patient out of there as fast as humanly possible, and sometimes this means sending people home with home nursing to get their 14 or 21 or 28 day course of vancomycin instead of sitting around on the ward letting their bacteria exchange plasmids with the bacteria on the other patients, in the walls, crawling all over the equipment, and (probably in the highest concentrations) in the computer keyboards that the hospital staff use.
But the biggest lesson: don't rely on antibiotics to kill virulent bacteria. The best defense is washing your hands frequently.
There are two drugs of last resort against Gram positive cocci, the group of bacteria that includes MRSA. These drugs, however, are usually used against vancomycin-resistant strains of Enterococcus. One is linezolid (Zyvox) and the other is dalfopristin/quinupristin (Synercid) There have been a few case reports of VISA (vancomycin-intermediate Staph aureus) and one or two case reports of VRSA (vancomycin-resistant Staph aureus), the most recent coming from Japan, but given how often we give vancomycin, it's a wonder that these strains aren't more widespread.
While hospital-acquired MRSA is typically resistant to everything except vancomycin, the community-acquired strain is actually quite sensitive to many older antibiotics like clindamycin, the tetracyclines, and sulfa antibiotics, so vancomycin resistance can be mitigated by using these as the first line against community-acquired skin infections, instead of using beta-lactams which are prone to failure and instead of admitting everyone to the hospital with suspected MRSA and immediately starting them on vancomycin.
Oh, and vancomycin actually acts quite similarly to the beta-lactams in that it interferes with bacterial cell wall synthesis by binding at an enzymatically targeted location (the D-Ala-D-Ala terminal of peptidoglycans), except that the specific mechanism which they intefere is slightly different.
Since vancomycin can only be given intravenously, it is typically only given in the hospital setting (or at home under the auspices of a home care nurse), and blood levels are closely monitored, making vancomycin actually a rather safe drug, although, like all drugs, it can have serious side effects (as you mention) that can be idiosyncratic.
While these bugs are pretty bad, particularly when you find them growing in a patient who is critically ill and already has other organ systems compromised (e.g., the typical ICU patient), they typically don't kill you right away. Like mentioned by Davak, Streptococcus pneumoniae (which, as the name implies, is the most common cause of bacterial pneumonia, but is also the most common cause of bacterial meningitis), Streptococcus pyogenes, and plain, run-of-the-mill, methicillin-sensitiveStaphylococcus aureus (the latter two can cause necrotizing fasciitis—they are the so-called flesh-eating bacteria) will all probably kill you much faster. Patients with these three can present perfectly well then become overwhelmingly septic then dead in less than 24 hours.
The ones mentioned in the article, however, are really all over the place and quite prevalent in the environment (yes, even MRSA—at least where I practice medicine, the prevalence rate of community-acquired MRSA is somewhere between 30-50% of all Staph infections. They are no longer exclusive to the hospital.) They generally don't cause problems in people who have intact immune systems and have intact normal flora. The reason you run into trouble is that patients who have these bugs growing in their bloodstream or eating their lungs are usually already very sick, which automatically means their immune systems are shot out. And if they've been sitting in the hospital for a while, chances are they've had their share of powerful antibiotics which have wiped out all their friendly, benign bacteria that often keep these bad actors in check.
The Gram-positive cocci that get resistant—Staph. aureus and the Enterococci—are still pretty much killable. If you get MRSA, the community-acquired variants still tend to be sensitive to other drug classes like clindamycin, the sulfas, and the tetracyclines. The hospital-acquired variant tends to be tougher, but there's always vancomycin. There have been a few reported cases of vancomycin-resistantStaph. aureus but there haven't been massive outbreaks—yet. Vancomycin-intermediate forms are more common, however. Then there's VRE (vancomycin-resistant Enterococcus). For these, you can use linezolid, and so far this works pretty well, although there have been isolated cases of resistance as well (though much less common than vancomycin resistance.) What freaks me out, though, is that we're starting to use this stuff like candy, especially since it's available as a pill.
The nastiest bugs, though, are the Gram negative rods, which include E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumanii. We tend to treat Pseudomonas with a lot of respect because it becomes rapidly resistant to antibiotics, and if we find it, or even just suspect it, we start off with two agents at least off the bat. Acinetobacter, on the other hand, is pervasive in the environment, and usually only starts causing problems when it has overgrown, usually in chronically-ill patients who have been in and out of the hospital a lot and who have gotten frequent antibiotics or, as mentioned, in ICU patients who have gotten multiple courses of antibiotics. The problem is that it is very hard to kill, since it is frequently multi-drug resistant and we often have to start out with big guns like meropenem. The abuse of penicillins and cephalosporins has caused an ncreasing prevalence of bacteria with extended-spectrum beta-lactamase activity, and even these big guns don't always do the trick against these puppies.
What scares me the most is the fact that there are really no new drug classes in the pipeline targetting Gram negative rods. The newest classes—fluoroquinolones, carbapenems, and monobactams—really haven't seen much development since the 1980s, and fluoroquinolones at least have already become
FYI, most medical missions to developing countries go for the purpose of vaccination. There's very little money to go around for medications, and sometimes they don't even bother, because a half-assed dose might be worse than no dose at all, given the resistance problem. It's the man with fishing pole thing. You give them antibiotics, they might get better for a few days, but likely they'll get reinfected once you leave. You give an immunization, it keeps them well for a good part of their life.
The only problem is that being on interferon is an ordeal. I worked with a hepatologist for a month when I was a medical student, and the people with Hep C he had on IFN looked half-dead, worse than chemo patients. And I also ran into people who had active Hep C with millions of copies per deciliter of blood floating around their body who told me they felt a lot better now that they stopped their IFN. Of course, there were people who were doing wonderfully on IFN, so there's obviously something to it, but it's not for everyone with Hep C.
You do realize that BCG is given to prevent disseminated disease, right? While it does nothing to prevent you from getting pulmonary TB, it does keep you from getting miliary TB or TB meningitis. If our four-drug regimen ever loses its effectiveness, I'm pretty sure we'll start giving BCG too.
Shoot, I just graduated from medical school and I've seen more than a couple of cases of active TB in the past year. I've even seen miliary TB and TB osteomyelitis. And this was in Chicago, not anywhere near the Mexican border.
Of course it may have more to do with socioeconomics. Asking about TB was routine at Cook County, but when I asked about it at an affluent community hospital, everyone looked at me like I was crazy. "You mean people still get TB?"
M. bovis can cause cavitary lung disease and disseminated disease just like M. TB. Clinically and microscopically, they are indistinguishable. The only difference is in method of transmission. While M. TB gets inhaled, M. bovis is usually eaten, found in unpasteurized dairy products.
M. avium usually doesn't pose a threat to people with intact immune systems, but it is a common AIDS-defining infection. There are also other Mycobacterium that are only usually found in AIDS like M. kansasii and M. scrofalaceum, but they pretty much paint the same picture.
The CDC recommends that a positive PPD despite BCG should be treated as a positive if BCG was administered more than five years ago. How valid that is, I don't know, but chances are you are going to have to go through isoniazid prophylaxis and get screening chest X-rays. Yay. Radiation. That said, I've seen some horrible reactions to PPD in people who had previous positives. I saw one woman with an arm that had swelled to a size as big as her head, and it was completely ulcerated and necrotic. But chances are she actually had TB, though, so it probably won't be that bad if you get a repeat PPD
Yeah, there was an article in the Chicago Reader a few months back, talking about how Hepatitis C is running rampant in the prison system. Hep C is like Hep B and HIV, in that it requires blood-borne transmission, but it is a lot hardier than HIV is, and can live on razor blades and kitchen utensils and such. So imagine that someone from prison gets paroled and is allowed to work at a fast food restaurant or something. Fun times.
Even better is the fact that there is no decent cure for Hep C right now. Sure, there's PEG-interferon and various other permutations, but the treatment takes a long time and is probably just as horrible if not worse than the disease itself--people on interferon look like they're dying. It might save their life and keep them from getting liver cancer, but it's not an easy thing to do.
Unlike most bacterial illnesses, which usually succumb to antibiotics within a month (or, if not, the patient generally succumbs within a month), TB takes a long time to kill. I've seen recommendations for treatment anywhere from six to twelve to twenty-four months. You stop anywhere before then, and I can guarantee that there are still some live red snappers partying away in your lung, just waiting to get spread to your blood and your brain. And giving antibiotics is basically artificial selection--evolution in fast forward. You will inevitably select for the bug that is most resistant to the drug you are giving. The only hope is to use two, three, or four drugs, and pray that you won't get unlucky and get more than one mutation at once.
The other problem is that TB is incredibly contagious. You can get infected by droplets that someone sneezed out hours ago still hanging in the air, bouncing around from Brownian motion, teeming with little acid-fast bacilli.
Yeah, the solution is called admission to the hospital for IV antibiotics. Unfortunately, that's really not realistic without some sort of universal health care.
But a lot of diseases don't require complicated dosing regimens. Pneumonia can often be treated by three days worth of azithromycin once a day. Uncomplicated urinary tract infections can also be treated in three days. Gonorrhea and syphilis pretty much only require one dose of antibiotics injected intramuscularly. It's really only in kids where the dosing regimens get crazy, sometimes requiring doses four times a day, for ten to fourteen days. That's where a lot of the drug resistance comes in, especially when insane parents demand antibiotics for their little kid's cold.
With regards to TB, though, you can be arrested for refusing to take your medications, for endangering the public. The more uncompliant patients will get DOT as mentioned above, and if you don't comply with that, you get admitted against your will for the duration of the therapy. (It's something like six or nine months, or maybe even a year--they keep lengthening it then shortening it then lengthening it then shortening it.) Your tax dollars at work, but I guess it's better than running into them on the subway or in an elevator when they're carrying around a strain that's resistant to all four of the commonly used drugs for treatment.
While the antibiotic class that has the most number of drugs on the market are based on penicillin (beta-lactams such as the penicillins, cephalosporins, and carbapenems), most of the modern drugs such as the macrolides, the fluoroquinolones, and the cell-wall-synthesis inhibitors like vancomycin and teicoplanin are based on entirely different mechanisms. (Although sadly, there is no one drug that can kill everything.)
In any case, though, in the olden days, they used isoniazid (abbreviated as INH). With emerging resistance, they started using two drugs simultaneously. And in this day and age, the first line of treatment for TB involves three drugs, usually INH, rifampin, and pyrazinamide (abbreviated as PZA.) A lot of times, though, we're super-cautious and use four drugs--either ethambutol or streptomycin, among others. None of these drugs are really used in treating other diseases--they're pretty specific for Mycobacterium. (So these drugs would be pretty good for leprosy and non-tuberculous Mycobacterial infections, too, but those organisms usually don't have the resistance profile that M.TB does, so we can usually go with less toxic drugs)
While misuse of antibiotics certainly is a major causative factor for why M.TB is so resistant, you've got to give the bug and evolution some credit too. TB is just so damn hard to kill. Your immune system can only really wall it off at best--without antibiotics, as soon as your immune system weakens, the bacteria just goes buck-wild, possibly causing disseminated disease like miliary TB or TB meningitis.
It is possible to live fine infected with TB as long as you have an intact immune system, but you're sort of like a ticking time bomb. Since immunity naturally wanes with age, when your old, you'll become contagious, and TB is really easy to transmit. Just think about all those people coughing in the subway or the elevator. Probability says you're going to run into one of them eventually.
This is an interesting idea which sounds plausible. It's well known that our circadian rhythm is driven by pulsatile activity of our pineal glands, as well as certain nuclei in the brain. And reproduction is impossible without pulsatile release of GnRH (gonadotropin releasing hormone) from the hypothalamus. In fact, menstrual cycles can be stopped by providing a continous level of GnRH, whereas a pulse of GnRH will restart them again. Where do these pulsatile mechanisms in the body derive their timing from? What if it's from the heart? After all, the heart is one of the earliest organs that start functioning in the embryoobstetricians generally use the lack of a heartbeat on ultrasound as a sign that a miscarriage has occurred. Who knows what pulsatile processes will be driven out of whack by eliminating cardiac pulsatility?
Well they have ECMO (extracorporeal membrane oxygenation) now, which can essentially replace the heart and lungs, but, as the acronym suggests, it's outside the body. So it's just the technical challenge of micronization, I think. I think merely replacing the heart is difficult because of its entanglement (anatomically and physiologically) with the lungs, which is evidenced by the fact that people do much better with combined heart-and-lung transplants than with just heart transplants. So if they get ECMO small enough, maybe we'll have a solution.
They do use artifical grafts to stop or prevent hemorrhage, but installing a Shrock shunt, which is basically a pipe driven down the superior vena cava through the right atrium into the inferior vena cava past the liver in order to stop/slow hemorrhage from the IVC from behind the liver, nonetheless usually results in death (about 98% mortality) and while they do abdominal aortic grafts, aortobifemoral grafts, and even crazy bypasses that connect your axillary arteries all the way to your femoral arteries, they rarely can do this in emergent settings where the patient is losing vast amounts of blood because (1) the blood really gets in the way of visibility and makes tying knots really difficult (2) it's sometimes hard to figure out where the ends of a blood vessel are when they've been shorn apart by an errant bullet or punctured by multiple knife stabs, especially when everything is covered in blood and (3) even if they manage to stop the bleeding and install a graft, often times it is difficult to maintain blood pressure in times of massive hemorrhage, even when infusing blood, blood products, and/or crystalloid fluids at rapid flow rates into multiple vessels. And when blood pressure drops for too long, cells start dying, including cardiac myocytes and vascular endothelial cells, resulting in an irreversibly damaged heart and severely damaged blood vessels. So even if you plug up the hole, the system you were trying to prop up might have already irreversibly collapsed.
Bear in mind that fully-equipped trauma surgeons with complete support teams are rarely found immediately at the site of a trauma incident. It usually takes at least some time to transport someone from where they got shot or stabbed to the OR, and you'd be surprised at how much blood you can lose in 30 seconds when your aorta is ripped in two or if your heart has a big hole in it.
So with these excuses aside, the reason people die from hemorrhage secondary to trauma is basically related to the degree of technical difficulty of such procedures and the unforgiving time limitations of human physiology, rather than lack of theoretical knowledge on the part of surgeons.
While you have it anatomically correct with regards to the cardiovascular system, you have it physiologically wrong. Varicose veins and portal hypertension are affected by cardiac function and pulsatility. While varicose veins are typically caused by gravity and portal hypertension is often caused by alcoholic cirrhosis independent of heart function, back pressures generated by a failing heart that does not generate effective contractility (systolic dysfunction) or fails to accomodate inflowing blood (diastolic dysfunction) makes these problems worse. In fact, you can get portal hypertension just because of right heart failure.
I think it's just a question of technology, specifically micronization. You can actually implant a left ventricle assist device into the body today, but it will probably be a few years before they can micronize current extra-corporeal membrane oxygenation (ECMO) devices so that they can fit in the body and completely replace a failed heart. As it is, you have to choose between relying on a bad ticker with an assist device, thereby still being able to move around a little, or relying entirely on ECMO and being tied down to a machine.
The other problem is that for either technique, you need anti-coagulation, which leads to a need for replacing red blood cells, platelets, and various coagulation cascade regulation factors. This study suggests that the replacement requirements for ECMO are much greater than that of ventricular assist, and, let me tell you, platelets aren't cheap, not to mention anti-thrombin III.
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Well, I don't know, I tend to think of medicine more as an applied science. It may not meet the definition of pure science, but it still does rely on advances in the pure sciences, it utilizes rational principles and logic, and there are a lot things about it that are reproducible and verifiable. Sure, it suffers from the interference of special interest groups that have other agenda, but I think it's still a far cry from completely non-scientific. And what science is free from such interference anyway?
One of the huge problems is that there are experiments that are doable that will never get funded, especially since there are various industries that have a vested interest in never discovering the answers to certain questions.
There is an enormous difference between the science of medicine and clinical practice.
The science of medicine—the science that figures out pathophysiology, that can determine which genes cause what diseases, what neuronal pathways cause what symptoms, what pharmaceutical agents cause what effects—this is regular science that follows the scientific method and is subject to peer-review.
What doctors do in the office, in the emergency room, and in the hospital are several steps removed from this. To use analogies to other fields, the science of medicine is to clinical practice as, say, what classical physics and materials science is to construction, what the science of semiconductors and electromagnetism is to computer manufacturing, or even what mathematics is to software development.
Clearly you cannot practice clinically without the basis of science, but it's not like you have to run randomized, controlled trials on your patients before you can treat any of them, any more than you need to design an experiment to calculate the value of G in order to build a skyscraper, or design a compiler before you can write a web app.
Clinical medicine is probably more about pattern recognition and the ability to estimate probability and apply Bayes' theorem even when you're missing key pieces of data (not to mention that its also more about empathy, compassion, and striving to make other people's lives better) This is where gut feelings sometimes come in, but still, treatment is generally based on rational principles, and perhaps just as important (at least in the modern era), the patient's informed consent. But science marches on, and doctors will always find that some of what they do is actually completely wrong.
The insurmountable issue is one of ethics. There are a lot of things that we will never be able to test simply because it would be unethical to do those experiments. So we're left with (in some cases) relying on the wisdom of experience, or with extrapolating principles that we can test, and sometimes just outright guessing (although always on the basis of the modern understanding of the processes occurring in the human body.) While doctors will sometimes miss the ruptured appendix, or the silent heart attack, you'll notice that they no longer subscribe to the idea of the four humors, of curing infectious disease by phlebotomizing patients, or treating asthma with urine injections.
The problem was that there were a ton of good, huge studies (still to be refuted) that show that serum cholesterol levels are good measures of predicting coronary artery disease.
What happened was that people assumed that it was simply a matter of diet. If you ate too much fat, your cholesterol levels would shoot through the roof, and you'd be more likely to get a heart attack.
What we are learning is that, while lower serum cholesterol does indeed seem to decrease your risk of rupturing that plaque in your coronaries (much to the joy of the pharmaceutical companies that make HMG-CoA reductase inhibitors), the hypothesis that eating tons of fat causes high cholesterol is not exactly bulletproof. There are obviously lots of other factors in play.
Still, I'm pretty loath to recommend a diet of, for example, nothing but bacon. I'm still pretty sure that eating bacon for breakfast, lunch, and dinner, 7 days a week, will most likely shorten your life.
I think one of the problems is that medical school curricula typically ignore the entire field of nutrition. Sure, they teach the biochemical reactions in which fats, proteins, and carbs are involved, but with regards to how this knowledge might actually be used to help patients, there is often a vast silence.
Add to this the fact that, in general, the medical establishment is extraordinarily conservative, and you end up with clinical practice that lags behind the basic science, and didactics that lag even farther behind clinical practice. So what you learn in med school is like 10 years behind what people actually do in clinical practice (although you may actually get pretty decent basic science if your school happens to have a lot of NIH grants, but, again, this is pretty useless if you actually intend to use this knowledge to treat people) and most clinicians tend to wait 10 years before they start believing anything that basic science and evidence-based medicine tells them (and that's if they even bother to read the big journals.)
Sure, digestion is a complex process and, yes, the laws of thermodynamics don't explain the intricacies of why people get fat and stay fat, but if you search PubMed on obesity, the uniform opinion is that, regardless of what kind of diet you eat, consuming more (kilo)calories than you use will cause you to get fat. This surely is not where the controversy is.
And in particular contexts (specifically illness, extreme stress, and starvation, sometimes also known as dieting), the body does use fat, carbs, and proteins equivalently: they will generally all get broken down in order to replenish the body's store of adenosine triphosphate (ATP), which is the body's true currency of energy, and the amount of ATP generated is proportionate to the amount of energy released by the breakdown of these substances into carbon dioxide, water, and (in the case of proteins), urea. Whatever doesn't get used to make ATP essentially gets shunted into the production of fat.
The big unknown is really how much of what you eat actually makes it into the bloodstream. Some of the variables of interest include intestinal transit time (high carb foods tend to pass through the GI tract faster than fatty and/or proteinaceous foods), time of transport across the intestinal lining (the breakdown products of carbs and proteins are generally more easily absorbed than fat, although not all fat is created equal), the exact composition of your intestinal flora (since the various organisms that live in your gut create all sorts of breakdown products, some of which can get reabsorbed and still used by your body), and the amount of enterohepatic circulation (even if the liver didn't catch it the first time around, it can still get reabsorbed farther down the tract and still actually get used), to name a few.
But what this really boils down to is the fact that the ideal 2,000 (kilo)calorie per day diet is just as fictional as the ideal 70 kg man, and has no specific bearing on whether a pound of potatoes will make you fatter than a 16 oz sirloin. Each of us has an individual energy set-point where usage and consumption are at equilibrium. Running this budget in the red makes us lose weight. Running this budget in the black makes us get fat. The problem is that we don't have a good way of figuring out where this set-point is, and even if we did, the body will always try its damndest to make you break even.
All forms of Staph aureus carry the toxin you mention, though, so there's really nothing to prevent you from getting MSSA necrotizing fasciitis.
And, yes, you pretty much need an intact immune system to successfully fight off infection. We can pump you full of every antibiotic known to man and cause every single bacteria in your system to explode, but without neutrophils and macrophages to clean up the resultant toxic mess, you're likely to eventually go into septic shock, which frequently means an eventual trip to the morgue.
Nonetheless, I think it demonstrates the importance of keeping your normal flora intact, and that means not demanding antibiotics when you don't need them.
As long as vancomycin can keep Staph aureus at bay, and as long as linezolid (which is available as a pill, and as such, is unfortunately being given out like candy) and dalfopristin/quinupristin (which is hardly ever used except in the sickest of patients and which is only available as IV) can keep VRE in check, we're actually in pretty good shape when it comes to Gram positive cocci. And this may last at least until the decade is out as long as we remain judicious with antibiotic use.
The bacterial pathogens that tend to be more virulent and cause us the most grief in the hospital are Gram negative rods such as E. coli, Pseudomonas, Actinobacter, and Stenotrophomonas, but I think a lot of this lies in the fact that we really haven't had any new drug classes that target GNRs in a really long time. Our drugs of last resort for these puppies are the carbapenems (imipenem, meropenem) and these are basically still based on the same mechanism as penicillin is, except they're more resistant to enzymatic degradation. I know there are new macrolides like telithromycin that are supposed to be better at taking care of GNRs, but macrolides are ridiculously easy for bacteria to figure out, and there is some theoretical concern that macrolide resistance can also confer resistance against our best anti-Gram postive cocci drugs (as above, linezolid and dalfopristin/quinupristin)
So if you want a Nobel Prize, get cracking on some new anti-Gram negative rod antibiotics.
Because hospitals are nothing but incubators for antibiotic resistance, physicians actually do their best to try to get their patient out of there as fast as humanly possible, and sometimes this means sending people home with home nursing to get their 14 or 21 or 28 day course of vancomycin instead of sitting around on the ward letting their bacteria exchange plasmids with the bacteria on the other patients, in the walls, crawling all over the equipment, and (probably in the highest concentrations) in the computer keyboards that the hospital staff use.
But the biggest lesson: don't rely on antibiotics to kill virulent bacteria. The best defense is washing your hands frequently.
While hospital-acquired MRSA is typically resistant to everything except vancomycin, the community-acquired strain is actually quite sensitive to many older antibiotics like clindamycin, the tetracyclines, and sulfa antibiotics, so vancomycin resistance can be mitigated by using these as the first line against community-acquired skin infections, instead of using beta-lactams which are prone to failure and instead of admitting everyone to the hospital with suspected MRSA and immediately starting them on vancomycin.
Oh, and vancomycin actually acts quite similarly to the beta-lactams in that it interferes with bacterial cell wall synthesis by binding at an enzymatically targeted location (the D-Ala-D-Ala terminal of peptidoglycans), except that the specific mechanism which they intefere is slightly different.
Since vancomycin can only be given intravenously, it is typically only given in the hospital setting (or at home under the auspices of a home care nurse), and blood levels are closely monitored, making vancomycin actually a rather safe drug, although, like all drugs, it can have serious side effects (as you mention) that can be idiosyncratic.
The ones mentioned in the article, however, are really all over the place and quite prevalent in the environment (yes, even MRSA—at least where I practice medicine, the prevalence rate of community-acquired MRSA is somewhere between 30-50% of all Staph infections. They are no longer exclusive to the hospital.) They generally don't cause problems in people who have intact immune systems and have intact normal flora. The reason you run into trouble is that patients who have these bugs growing in their bloodstream or eating their lungs are usually already very sick, which automatically means their immune systems are shot out. And if they've been sitting in the hospital for a while, chances are they've had their share of powerful antibiotics which have wiped out all their friendly, benign bacteria that often keep these bad actors in check.
The Gram-positive cocci that get resistant—Staph. aureus and the Enterococci—are still pretty much killable. If you get MRSA, the community-acquired variants still tend to be sensitive to other drug classes like clindamycin, the sulfas, and the tetracyclines. The hospital-acquired variant tends to be tougher, but there's always vancomycin. There have been a few reported cases of vancomycin-resistant Staph. aureus but there haven't been massive outbreaks—yet. Vancomycin-intermediate forms are more common, however. Then there's VRE (vancomycin-resistant Enterococcus). For these, you can use linezolid, and so far this works pretty well, although there have been isolated cases of resistance as well (though much less common than vancomycin resistance.) What freaks me out, though, is that we're starting to use this stuff like candy, especially since it's available as a pill.
The nastiest bugs, though, are the Gram negative rods, which include E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumanii. We tend to treat Pseudomonas with a lot of respect because it becomes rapidly resistant to antibiotics, and if we find it, or even just suspect it, we start off with two agents at least off the bat. Acinetobacter, on the other hand, is pervasive in the environment, and usually only starts causing problems when it has overgrown, usually in chronically-ill patients who have been in and out of the hospital a lot and who have gotten frequent antibiotics or, as mentioned, in ICU patients who have gotten multiple courses of antibiotics. The problem is that it is very hard to kill, since it is frequently multi-drug resistant and we often have to start out with big guns like meropenem. The abuse of penicillins and cephalosporins has caused an ncreasing prevalence of bacteria with extended-spectrum beta-lactamase activity, and even these big guns don't always do the trick against these puppies.
What scares me the most is the fact that there are really no new drug classes in the pipeline targetting Gram negative rods. The newest classes—fluoroquinolones, carbapenems, and monobactams—really haven't seen much development since the 1980s, and fluoroquinolones at least have already become
FYI, most medical missions to developing countries go for the purpose of vaccination. There's very little money to go around for medications, and sometimes they don't even bother, because a half-assed dose might be worse than no dose at all, given the resistance problem. It's the man with fishing pole thing. You give them antibiotics, they might get better for a few days, but likely they'll get reinfected once you leave. You give an immunization, it keeps them well for a good part of their life.
The only problem is that being on interferon is an ordeal. I worked with a hepatologist for a month when I was a medical student, and the people with Hep C he had on IFN looked half-dead, worse than chemo patients. And I also ran into people who had active Hep C with millions of copies per deciliter of blood floating around their body who told me they felt a lot better now that they stopped their IFN. Of course, there were people who were doing wonderfully on IFN, so there's obviously something to it, but it's not for everyone with Hep C.
You do realize that BCG is given to prevent disseminated disease, right? While it does nothing to prevent you from getting pulmonary TB, it does keep you from getting miliary TB or TB meningitis. If our four-drug regimen ever loses its effectiveness, I'm pretty sure we'll start giving BCG too.
Of course it may have more to do with socioeconomics. Asking about TB was routine at Cook County, but when I asked about it at an affluent community hospital, everyone looked at me like I was crazy. "You mean people still get TB?"
M. avium usually doesn't pose a threat to people with intact immune systems, but it is a common AIDS-defining infection. There are also other Mycobacterium that are only usually found in AIDS like M. kansasii and M. scrofalaceum, but they pretty much paint the same picture.
The CDC recommends that a positive PPD despite BCG should be treated as a positive if BCG was administered more than five years ago. How valid that is, I don't know, but chances are you are going to have to go through isoniazid prophylaxis and get screening chest X-rays. Yay. Radiation. That said, I've seen some horrible reactions to PPD in people who had previous positives. I saw one woman with an arm that had swelled to a size as big as her head, and it was completely ulcerated and necrotic. But chances are she actually had TB, though, so it probably won't be that bad if you get a repeat PPD
Even better is the fact that there is no decent cure for Hep C right now. Sure, there's PEG-interferon and various other permutations, but the treatment takes a long time and is probably just as horrible if not worse than the disease itself--people on interferon look like they're dying. It might save their life and keep them from getting liver cancer, but it's not an easy thing to do.
The other problem is that TB is incredibly contagious. You can get infected by droplets that someone sneezed out hours ago still hanging in the air, bouncing around from Brownian motion, teeming with little acid-fast bacilli.
But a lot of diseases don't require complicated dosing regimens. Pneumonia can often be treated by three days worth of azithromycin once a day. Uncomplicated urinary tract infections can also be treated in three days. Gonorrhea and syphilis pretty much only require one dose of antibiotics injected intramuscularly. It's really only in kids where the dosing regimens get crazy, sometimes requiring doses four times a day, for ten to fourteen days. That's where a lot of the drug resistance comes in, especially when insane parents demand antibiotics for their little kid's cold.
With regards to TB, though, you can be arrested for refusing to take your medications, for endangering the public. The more uncompliant patients will get DOT as mentioned above, and if you don't comply with that, you get admitted against your will for the duration of the therapy. (It's something like six or nine months, or maybe even a year--they keep lengthening it then shortening it then lengthening it then shortening it.) Your tax dollars at work, but I guess it's better than running into them on the subway or in an elevator when they're carrying around a strain that's resistant to all four of the commonly used drugs for treatment.
In any case, though, in the olden days, they used isoniazid (abbreviated as INH). With emerging resistance, they started using two drugs simultaneously. And in this day and age, the first line of treatment for TB involves three drugs, usually INH, rifampin, and pyrazinamide (abbreviated as PZA.) A lot of times, though, we're super-cautious and use four drugs--either ethambutol or streptomycin, among others. None of these drugs are really used in treating other diseases--they're pretty specific for Mycobacterium. (So these drugs would be pretty good for leprosy and non-tuberculous Mycobacterial infections, too, but those organisms usually don't have the resistance profile that M.TB does, so we can usually go with less toxic drugs)
While misuse of antibiotics certainly is a major causative factor for why M.TB is so resistant, you've got to give the bug and evolution some credit too. TB is just so damn hard to kill. Your immune system can only really wall it off at best--without antibiotics, as soon as your immune system weakens, the bacteria just goes buck-wild, possibly causing disseminated disease like miliary TB or TB meningitis.
It is possible to live fine infected with TB as long as you have an intact immune system, but you're sort of like a ticking time bomb. Since immunity naturally wanes with age, when your old, you'll become contagious, and TB is really easy to transmit. Just think about all those people coughing in the subway or the elevator. Probability says you're going to run into one of them eventually.
This is an interesting idea which sounds plausible. It's well known that our circadian rhythm is driven by pulsatile activity of our pineal glands, as well as certain nuclei in the brain. And reproduction is impossible without pulsatile release of GnRH (gonadotropin releasing hormone) from the hypothalamus. In fact, menstrual cycles can be stopped by providing a continous level of GnRH, whereas a pulse of GnRH will restart them again. Where do these pulsatile mechanisms in the body derive their timing from? What if it's from the heart? After all, the heart is one of the earliest organs that start functioning in the embryoobstetricians generally use the lack of a heartbeat on ultrasound as a sign that a miscarriage has occurred. Who knows what pulsatile processes will be driven out of whack by eliminating cardiac pulsatility?
Well they have ECMO (extracorporeal membrane oxygenation) now, which can essentially replace the heart and lungs, but, as the acronym suggests, it's outside the body. So it's just the technical challenge of micronization, I think. I think merely replacing the heart is difficult because of its entanglement (anatomically and physiologically) with the lungs, which is evidenced by the fact that people do much better with combined heart-and-lung transplants than with just heart transplants. So if they get ECMO small enough, maybe we'll have a solution.
Bear in mind that fully-equipped trauma surgeons with complete support teams are rarely found immediately at the site of a trauma incident. It usually takes at least some time to transport someone from where they got shot or stabbed to the OR, and you'd be surprised at how much blood you can lose in 30 seconds when your aorta is ripped in two or if your heart has a big hole in it.
So with these excuses aside, the reason people die from hemorrhage secondary to trauma is basically related to the degree of technical difficulty of such procedures and the unforgiving time limitations of human physiology, rather than lack of theoretical knowledge on the part of surgeons.
While you have it anatomically correct with regards to the cardiovascular system, you have it physiologically wrong. Varicose veins and portal hypertension are affected by cardiac function and pulsatility. While varicose veins are typically caused by gravity and portal hypertension is often caused by alcoholic cirrhosis independent of heart function, back pressures generated by a failing heart that does not generate effective contractility (systolic dysfunction) or fails to accomodate inflowing blood (diastolic dysfunction) makes these problems worse. In fact, you can get portal hypertension just because of right heart failure.
The other problem is that for either technique, you need anti-coagulation, which leads to a need for replacing red blood cells, platelets, and various coagulation cascade regulation factors. This study suggests that the replacement requirements for ECMO are much greater than that of ventricular assist, and, let me tell you, platelets aren't cheap, not to mention anti-thrombin III.