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 +4  (free120#15)

Rituximab (anti-CD 20) is currently undergoing trials for AS. My sparse googling just now shows that rituximab probably only has a moderate effect, so probably second-line to anti-TNFa therapy. Probably.

Safe to say for boards that AS: TNFa > CD20


 +1  (free120#9)

I believe (pls correct me if I'm wrong) you would have similar Southern blot results seen in B cells undergoing somatic hypermutation, but that takes place in the secondary lymphoid tissue, not in the bone marrow.





Subcomments ...

DMD is X-linked. We know her mom is a carrier based on family history, supported by lab testing. But her mom has 2 X chromosomes, only one of which is mutated. There is no way to know which her daughter eventually receives and expresses by her phenotype (i.e if she is a carrier or not). Just because her CK is normal doesn’t mean she isn’t a carrier–the phenotype of the X-linked carrier depends on X-inactivation.

em_goldman  Is X-inactivation not randomly mosaic throughout tissues? My thinking is that random, evenly-distributed X activation would cause about ~half symptoms (ex Rett syndrome, X-linked dominant fatal in utero in males but survivable in females due to X-inactivation.) So you see her mom with (presumed) isolated increased CK, which you would expect in her if she was also a carrier. Maybe penetration is variable so you'd need genetic testing to confirm for sure -> the reason she doesn't have symptoms is x-inactivation. +  


The main downside of live vaccines is that they can (but rarely do) cause the disease they’re designed to prevent, typically in immune-compromised individuals, who either receive the vaccine or are a close contact of someone who did.

em_goldman  Also in the case of the live oral polio vaccine, there's concern of viral reactivation in the feces of people who took the vaccine causing infection of others, even if the original person is protected. I would guess rotavirus is similar but I think the population risk:benefit favors live rotavirus vaccination in lieu of no vaccination, whereas the option of a killed polio virus vaccination is way more worth it than the risk of a polio virus outbreak. +  


submitted by houseppary(2),

but what is wrong with "Spirochete invasion of gastric cells"? It seems like H pylori is sometimes described as curved and sometimes as a spirochete. And "gastric cells" is general enough that I don't see why it can be wrong. There is H pylori in the gastric cells.

em_goldman  H pylori is sometimes described as helical but more often as curved, but is (confusingly) not a spirochete. Spirochete refers to a particular family, Spirochaete, and are markedly corkscrew. The three important spirochete bugs for Step 1 are Leptospira, Borrelia spp., and Treponema pallidum; Brachyspira spp. get an honorable mention but idk they're high yield for Step 1. Anything other kind of bug is not going to be a spirochete. Additionally, H. pylori is not invasive, and instead resides on the surface of the gastric mucosa. The picture showed some bacteria inside the lumen of glands, not intracellulary. +1  
em_goldman  *idk if they're high yield +  
em_goldman  *any other kind of bug gosh dang it, lol, definitely in dedicated rn +  


submitted by houseppary(2),

but what is wrong with "Spirochete invasion of gastric cells"? It seems like H pylori is sometimes described as curved and sometimes as a spirochete. And "gastric cells" is general enough that I don't see why it can be wrong. There is H pylori in the gastric cells.

em_goldman  H pylori is sometimes described as helical but more often as curved, but is (confusingly) not a spirochete. Spirochete refers to a particular family, Spirochaete, and are markedly corkscrew. The three important spirochete bugs for Step 1 are Leptospira, Borrelia spp., and Treponema pallidum; Brachyspira spp. get an honorable mention but idk they're high yield for Step 1. Anything other kind of bug is not going to be a spirochete. Additionally, H. pylori is not invasive, and instead resides on the surface of the gastric mucosa. The picture showed some bacteria inside the lumen of glands, not intracellulary. +1  
em_goldman  *idk if they're high yield +  
em_goldman  *any other kind of bug gosh dang it, lol, definitely in dedicated rn +  


submitted by houseppary(2),

but what is wrong with "Spirochete invasion of gastric cells"? It seems like H pylori is sometimes described as curved and sometimes as a spirochete. And "gastric cells" is general enough that I don't see why it can be wrong. There is H pylori in the gastric cells.

em_goldman  H pylori is sometimes described as helical but more often as curved, but is (confusingly) not a spirochete. Spirochete refers to a particular family, Spirochaete, and are markedly corkscrew. The three important spirochete bugs for Step 1 are Leptospira, Borrelia spp., and Treponema pallidum; Brachyspira spp. get an honorable mention but idk they're high yield for Step 1. Anything other kind of bug is not going to be a spirochete. Additionally, H. pylori is not invasive, and instead resides on the surface of the gastric mucosa. The picture showed some bacteria inside the lumen of glands, not intracellulary. +1  
em_goldman  *idk if they're high yield +  
em_goldman  *any other kind of bug gosh dang it, lol, definitely in dedicated rn +  


Southern blots are commonly used in immunological studies, as the southern blot allows for the study of DNA alterations. What is normally one gene configuration related to immune globulins in most tissues demonstrates multiple different bands in the bone marrow, indicative of gene rearrangement. This is basically how we create new antibodies. Reactive processes are polyclonal (multiple bands); leukemia, in contrast, is monoclonal (single band).

ali  I still don’t understand this one. Could you provide a better explanation? +  
benwhite_dotcom  The cDNA tag is tagging a constant region common to immunoglobulins, so it normally only finds the one band corresponding to that particular gene (the bands travel different amounts due to their differing size/weight). In the bone marrow sample, that gene has rearranged itself, so the cDNA clone instead tags multiple different genes that are of different sizes on the gel (each one has that same constant region the cDNA is tagging, but with different stuff around it such that the restriction enzyme has cut it up differently). I’d be happy for someone to step in and do a better job on that explanation. +3  
em_goldman  A Southern blot starts by cutting DNA strands at a particular (short) site and running them through gel electrophoresis, so identical DNA sequences get cut at the same site and thus are the same length, so they are at the same place on the gel. If there's lots of different sequences, the restriction endonuclease (the scissors) cut the DNA at different places, leading to strands that were the same length originally but are now lots of different lengths -> different places on the gel. But how do you know this is the same gene, just with different mutations? The Southern blot uses a probe to look for a more specific (long) region of DNA that you know is in the target gene. So even though there are mutations causing the less-specific endonuclease to cut the DNA at different parts, the overall architecture of the gene is similar enough that the probe can bind, thus we know it's the same gene. (And in bone marrow WBCs, the mechanism here is genetic rearrangement.) +  


Filgrastim is a granulocyte colony stimulating factor (GCSF), which are drugs used to increase white blood cell count in patients with leukopenia. Leucovorin (folinic acid) sounds like it would also be right, but it’s used to prevent bone marrow suppression in patients taking methotrexate. Darbepoetin (like erythropoietin) is used to stimulate red blood cell production.

em_goldman  were we supposed to know that she wasn't taking methotrexate (or did I miss that in the question stem)? +  


submitted by poisonivy(9),

can we consider the overdose as a suicidal attempt? if so... wouldn't she be considered as without decision-making capacity?

em_goldman  People who are suicidal still have decision-making capacity; it's not equivalent to advanced dementia or other situations where decision making is impaired. Laws vary by state; I know in my state that the maximum time for holding someone against their will is 48 hours unless a court has deemed them incompetent and designated another person as their legal decision maker, including people who are actively suicidal. My understanding of the law as a layperson is that her living will was signed along with people bearing witness to the fact that she was the one who signed it, and it was what she wanted. Ethics aside, it would be almost impossible to prove that she legally initiated a DNR in a state of suicidality that was intense enough to interfere with her decision-making capacity in that moment. +