Never bet against occam, p.57
Never Bet Against Occam, page 57
Pulmonary embolus
“Pul´-moh-nār´-ee em´-bōl-us.” More commonly referred to by its “PE” initials, a pulmonary embolus (plural: pulmonary emboli, “pul´-moh-nār´-ee em´-bōl-ī”) is a blood clot in the pulmonary artery (leading from the heart’s right ventricle to the lungs) or one of its branches. If it’s a big enough clot that blocks enough blood flow to the lungs, a PE of course can be (rapidly!) fatal. As abnormal blood clotting is a common complication of inflammation, some mast cell disease patients have a tendency toward excessive blood clotting and thus suffer, or at least are at risk for suffering, a PE. Doctors are well trained to consider the possibility of a PE when a patient complains of shortness of breath, particularly when it’s of acute onset and accompanied by chest pain.
Pulmonic valve
“Pul-mon´-ik” valve. The pulmonic valve sits at the base of the pulmonary artery which provides the conduit for blood being pumped out of the heart’s right ventricle to travel to the lungs in order to off-load waste carbon dioxide and pick up a fresh supply of oxygen. Without the presence and proper operation of the (one-way) pulmonic valve, a lot of the blood pumped forward into the pulmonary artery with each beat of the heart (i.e., with each contaction of the right ventricle) would simply fall back into the right ventricle, dramatically reducing blood flow to the lungs and causing substantial impairment in delivery of oxygen to tissues throughout the body. This causes fast breathing (tachypnea) and a bluish discoloration of the skin.
Pulmonology
“Pul´-mon-ol´-oh-jee.” This is the study of the lungs, or the specialty focusing in lung disease.
Pure red cell aplasia
Pure red cell “ā´-plā´-zha.” Sometimes known by its “PRCA” initials, pure red cell aplasia is a disease in which the bone marrow at least temporarily (and sometimes, more seriously, permanently) stops making red blood cells, while production of other types of blood cells remains essentially unimpaired. PRCA is usually caused by an infection of red blood cell precursor cells in the bone marrow called pronormoblasts, and it’s usually a virus called parvovirus B-19 that’s the culprit in such infections. Sometimes, though, PRCA can be caused by other mechanisms, including autoimmune disorders (typically seen in conjunction with a rare type of cancer of the thymus gland in the center of the chest (i.e., in the mediastinum) called a thymoma) as well as severe inflammatory conditions. Rarely, mast cell disease can produce such strong inflammation as to cause the appearance of PRCA.
Pyridostigmine
“Pir´-ih-doh-stig´-meen.” Known more commonly by its most popular U.S. trade name Mestinon, pyridostigmine is an inhibitor of a key enzyme for proper nerve cell functioning called cholinesterase. It’s used to treat the rare autoimmune neurologic condition called myasthenia gravis, to treat postural orthostatic tachycardia syndrome (POTS), and to reverse the effects of exposure to certain “nerve gas”-type chemical warfare agents.
Q
Quercetin
“Kwer´-seh-tin.” Quercetin is a natural component of many foods, especially certain vegetables such as broccoli. It is a type of molecule classified as a “flavonoid” that has anti-inflammatory properties. It is available as an inexpensive over-the-counter “supplement” and can help some patients with mast cell disease. The precise mechanisms by which it inhibits mast cell activity (at least in some patients) are unclear.
R
Radiotherapy
“Rā´-dee-oh-ther´-uh-pee.” Simply put, radiotherapy is treatment of a disease (usually cancer) by radiation of one type or another.
Ranitidine
“Ruh-ni´-ti-deen.” Also known by its most popular trade name Zantac, the drug ranitidine is a histamine H2 receptor blocker (see the entry for “histamine” for more information). Ranitidine has more drug-drug interactions than the other most popular H2 blocker, famotidine.
Red cell distribution width
Standard English words there, no tricky pronunciation, but it is a bit tricky to explain what the “RDW” actually is. The RDW is one of the numbers usually reported on a complete blood count (CBC), and simply put, it’s a measure of how monotonously sized the red blood cells in the blood sample are. If most of the red blood cells in the sample are about the same size (regardless of whether that size is normal (normocytic), larger than normal (macrocytic), or smaller than normal (microcytic)), then the RDW will be normal. As the number of red blood cells of sizes different from the average size increases in the sample, the RDW increases. Putting together the hemoglobin, hematocrit, the red blood cell count, the average red blood cell size (otherwise known as the mean corpuscular volume, or MCV), and the RDW – especially when trends of these numbers are available – can often give the doctor a pretty good idea of how well red blood cell production in the bone marrow is working, including some ideas of specific underlying causes if there are abnormalities seen in any of these parameters.
Relapsing polychondritis
Relapsing “pol´-ee-kon-drīt´-is.” Sometimes known by its “RP” initials, relapsing polychondritis is a rare multisystem condition, usually diagnosed and managed by rheumatologists, most prominently featuring chronic inflammation of unknown cause affecting a type of connective tissue present widely throughout the body called cartilage. Many of the symptoms of RP mimic what can be seen in MCAD, and since nobody knows the cause of RP, it’s possible that some variant of MCAD is the underlying issue in some portion of the RP population. (Another project for the research pile, eh?)
Retinitis
“Ret´-in-īt´-is.” Simply put, retinitis is inflammation (“-itis”) of the retina, the thin tissue at the back of the eye that transforms light into electrical impulses that travel down the optic nerve to the brain, which interprets those impulses as the images we see. As such, retinitis usually causes visual impairment. If not identified and corrected soon enough, it can cause permanent blindness.
Rheumatoid arthritis
“Room´-uh-toid” arthritis. Often referred to by its “RA” initials, rheumatoid arthritis is a particular (and common) type of inflammatory condition most commonly affecting the joints but sometimes also other tissues such as the lungs.
Rheumatology
“Room´-uh-tol´-oh-jee.” Rheumatology is the study of joints and connective tissues, or the medical specialty focusing in diseases of the joints (such as arthritis) and connective tissues including the “collagen vascular disorders” (such as lupus). Given the generally inflammatory theme with which mast cell disease commonly presents, it’s not surprising that many MCAD patients have been previously evaluated by a rheumatologist before their MCAD is diagnosed.
Rhinosinusitis
“Rī´-noh-sīn´-yoo-sīt´-is.” Simply put, this is inflammation (“-itis”) of the nose (“rhino-”) and sinuses. Especially given that mast cells tend to site themselves at the environmental interfaces and then abnormally produce and release inflammatory mediators, rhinosinusitis is a common complication of mast cell disease.
Rhizotomy
“Rī-zot´-oh-mee.” A rhizotomy is a surgical procedure in which selected nerve roots emerging from the spinal cord are destroyed (typically by simply severing them) in an effort to relieve symptoms of dysfunction in such nerves such as various spastic and pain conditions.
Ribonucleic acid
“Rī´-boh-noo-clā´-ik” acid. Far more commonly referred to by its abbreviation RNA, ribonucleic acid is the critical intermediate between a specific strand of DNA (i.e., a specific gene) and the specific protein coded for by that specific strand of DNA. The string of DNA that defines a gene is transcribed into a corresponding string of RNA, and that string of RNA is then translated into a corresponding string of amino acids which define a given protein and which can actually accomplish things inside a cell. The discovery (by the team at the University of Bonn led by Dr. Gerhard Molderings) that virtually every MCAS patient bears mutations in the KIT protein in the patient’s mast cells was made by analyzing sequences of KIT RNA extracted from such patients’ mast cells.
Right upper quadrant
Standard English words there, no tricky pronunciation. Often abbreviated as RUQ, this simply refers to the right upper part of the abdomen, where such parts of the anatomy as the liver and gallbladder are usually found. Thus, RUQ pain or swelling can be sign of a problem in the liver and/or gallbladder, but it also can be a sign of a problem in other structures in the area such as the small or large intestinal tract.
Risedronate
“Ris-eh´-drōn-āt.” Known more widely by its most popular U.S. trade name Actonel, risedronate is yet another bisphosphonate for protecting bones against weakening. It’s taken orally, typically once a week or even once a month.
RNA
See Ribonucleic acid.
Rohypnol
“Roh-hip´-nol.” The most commonly recognized trade name in the U.S. for flunitrazepam. See Flunitrazepam.
Rosette
“Roh-zet´.” In its most basic meaning, a rosette simply is a pattern in which a given sub-pattern is replicated and arrayed around a central feature. In medicine, the word is usually applied to a cellular pattern in which a certain type of cell (typically a red blood cell) is arrayed around a cell (which may be the same type, or a different type, of cell (such as another red blood cell, or a white blood cell). Red blood cell rosetting can be a sign of certain conditions or diseases such as a difference in the Rh blood type between mother and fetus, or the presence of malaria.
S
Salmonella
“Sal´-moh-nel´-uh.” Salmonella is a class of common bacteria. Some of the specific bacteria in this class can cause food poisoning. Because a flare of MCAD can sometimes mimic an incident of food poisoning, some MCAD patients – usually before they’re actually diagnosed with MCAD – come to be suspected of suffering Salmonella-based food poisoning. Of course, since MCAD can interfere with proper functioning of the immune system and thus render the patient more susceptible to infection, true Salmonella infections are possible in an MCAD patient (just like in somebody who doesn’t have MCAD), but in my experience such infections are no more common in MCAD patients than in people who don’t have MCAD.
Sandimmune
“Sand ´-im-yoon.” Trade name for a formulation of cyclosporine commonly used in the U.S. See Cyclosporine.
Sarcoid
“Sar´-coid.” Also known as sarcoidosis, sarcoid is yet another interesting inflammatory disease of unknown origin despite decades of study. It’s usually just an acute issue that resolves on its own, but sometimes it becomes a chronic disease which can progress to a fatal point. Sarcoid features abnormal collections of inflammatory cells, known as granulomas, that accumulate in various organs such as the lungs and lymph nodes. As is the case regarding many chronic idiopathic inflammatory diseases, I have my suspicions that, at least in some sarcoid patients, MCAD is the root issue. (Yes, add this one, too, to the list of research projects to be done.)
Satiety
“Suh-tī´-eh-tee.” Satiety is a sense of fullness. “Early satiety” is when you get a sense of fullness during eating sooner than you’d expect to based on how much you ate, and it can be a sign of any of a number of problems including a stomach cancer or an enlarged spleen or liver.
Sclerae
“Skler´-ī.” The whites of the eyes, surrounding the colored iris. These areas can assume other colors in various states of illness, such as a yellow-brown color when an excess of bilirubin accumulates in the blood, or a bloody red when there is bleeding into the sclerae (a condition called a hyphema). Sometimes a pattern of engorged tiny blood vessels comes to stand out against the white fields; this is an inflammation of the sclerae called scleritis, or scleral conjunctivitis. MCAD occasionally causes various problems that lead to abnormal coloring of the sclerae.
Scopolamine
“Scoh-pol´-uh-meen.” Also known by its popular trade name Dramamine, this drug is a sedating histamine H1 receptor blocker (see “histamine” for more information). Its most widely known use is to prevent the nausea of seasickness.
Secretin stimulation test
“See´-kreh-tin” stimulation test. This is a test, usually administered by gastroenterologists, that helps detect whether a rare type of neuroendocrine cancer called a gastrinoma is present. Gastrinomas, usually located in the stomach, produce the hormone gastrin in an unregulated fashion. Gastrin drives the acid-producing cells of the stomach – the parietal cells – to produce acid. As you might imagine, ordinarily the production of acid is a highly regulated process, but the production of gastrin by a gastrinoma is an unregulated process, and thus the stomach makes far more acid than it should, and this leads to problems of ulcers (which sometimes bleed) and abdominal pain even apart from the basic problem that a gastrinoma is a cancer that can spread (metastasize) and eventually kill the patient. Ordinarily, the stomach’s parietal cells turn down their production of gastrin when they sense an increased level in the blood of another hormone, secretin. (Secretin, as you might expect, is produced by certain specialized cells in the duodenum (just a little ways down the intestinal tract from the stomach), where they are perfectly positioned to sense stomach acid production and increase secretin production if the juices coming down the intestinal tract from the stomach are getting too acidic.) Of course, since production of gastrin by gastrinoma tumor cells – as opposed to parietal cells – is unregulated, there is no suppression of acid production by gastrinoma tumor cells when the secretin level increases. Therefore, you can now imagine how the secretin stimulation test works. After a catheter that can measure acidity is threaded through the patient’s nose or mouth, down through the throat, esophagus, and stomach and finally into the duodenum, the baseline acidity level is measured and then secretin is infused into the patient’s bloodstream while the acidity level continues to be monitored. If there is no gastrinoma present, the acidity should ease up as the secretin infusion continues, but if the juices persist in being just as acidic as they were at baseline in spite of the secretin infusion, then it’s a pretty good bet that a gastrinoma is present. Because MCAD often leads to excessive levels of acid production that can lead to ulcer disease, sometimes a gastrinoma is suspected before MCAD is suspected, and thus an occasional MCAD patient comes to have a secretin stimulation test done as part of the thousand (or two) tests they undergo, over years and years, to try to figure out why they’re so sick in so many different ways.
Septicemia
“Sep´-ti-seem´-ee-uh.” Septicemia is the general term for infection (usually by bacteria, though sometimes by a fungus or another unusual microorganism) that’s present in the blood. Without effective treatment, septicemia is often fatal. There are many different paths by which MCAD can (fortunately only occasionally) lead to septicemia.
Serotonin reuptake inhibitors
“Seer´-oh-tōn´-in re-up´-tāk” inhibitors. Also known as selective serotonin reuptake inhibitors, or SSRIs, these very commonly prescribed medications were developed to treat depression and generally have been pretty successful at doing so. It was originally thought that the SSRIs treat depression by blocking “serotonin reuptake elements” (SREs) on the surfaces of presynaptic nerve cells, thereby increasing the amount of the signaling molecule serotonin in the neural synapse available for binding to, and thus activating of, post-synaptic nerve cells, and by stimulating such post-synaptic neural activity, depression can be lifted. In more recent times we’ve been discovering the presence of SREs on the surfaces of other cells, too, including – you guessed it – the mast cell. Therefore, whether it’s through stimulating nerve cells which then help settle down hyperactive mast cells, or by directly binding with and inhibiting hyperactive mast cells, it’s not surprising that SSRIs help settle down at least some mast-cell-related symptoms in some MCAD patients. Commonly prescribed SSRIs include fluoxetine (Prozac) and paroxetine (Paxil), but there are lots of other SSRIs that have been developed and approved for marketing.
Serotonin
“Seer´-oh-tōn´-in.” This is a key signaling molecule in regulating activity of nerve cells, and we’ve been learning more recently that it also binds to, and thus participates in the regulation of, many other types of cells, too, including mast cells.
Sickle cell anemia
Standard English words there, no tricky pronunciation. This is an inherited disease in which a single mutation in the gene for making beta globin (one of the components of hemoglobin) leads to the formation of an abnormal hemoglobin molecule that’s unusually sticky when it doesn’t have a molecule of oxygen that’s bound to it. As a result, in a poor-oxygen environment (such as the blood that’s found in veins as opposed to arteries), these abnormal hemoglobin molecules stick to one another, causing hemoglobin to clump up instead of floating apart from one another in the fluid environment inside the red blood cell, and such clumping, or polymerizing, causes the red blood cell to deform in a way that, when visualized through a microscope, resembles a sickle. When red blood cells deform in this way, they don’t flow through the tiniest blood vessels, called capillaries, in normal fashion. In fact, they get stuck in, and plug up, the capillaries, which obvious impairs blood flow through those capillaries and thus impairs delivery of oxygen and other nutrients that blood brings to the various tissues throughout the body. Unsurprisingly, as tissues starve for oxygen and nutrients, they start dying, and it hurts. This is the sickle cell pain crisis that you may have heard about, and it is pure misery. The curious thing about sickle cell anemia, though, is that even though every sickle cell anemia patient has exactly the same beta globin mutation, roughly 15% of such patients have a really rough course (a “poor phenotype”) of the disease, while the other 85% or so have a much easier time (though certainly no picnic), implying that there must be something else going on in the 15% that makes their course so much worse. A few years ago I began realizing that most poor-phenotype sickle cell anemia patients have symptoms that are much easier for MCAS to explain than sickle cell anemia, and when I tested them for MCAS, I found it in most of them, and I also began finding that treating such MCAS would sometimes enable a poor-phenotype sickle cell anemia patient to “transform” into a good-phenotype sickle cell anemia patient. (Yes, I did eventually publish these findings, in the American Journal of the Medical Sciences in late 2014.) Of course, there remains a great amount of further research to be done in this area.
