text:
The Case
You have a 54-year-old female who presents to the emergency department with a chief complaint of "just feeling out of it." She has felt "off and on" for the past 12 hours and has had an occasional cough with some sputum production along with "the shakes and chills." She also feels as if her heart was "going at a mile a minute" and because of this, she is very much out of breath.
She has a past medical history of hypertension and she has been compliant with her medications. She also tells you that she has had recent blood work ordered by her primary care physician that was highly suspicious for "some sort of thyroid disorder", but the results have not been made known to her yet.
Physical Exam
Her vital signs are blood pressure of 184/106 mmHg, heart rate of 130 beats per minute, respiratory rate of 22 breaths per minute, and temperature of 102.7°F. She seems relatively anxious on physical exam, and you note that she is diaphoretic. An EKG is ordered, revealing an irregularly irregular rhythm, and an urinalysis is conducted, showing many bacteria. You decide to pan-culture her and determining that she has no known drug allergies, you order a combination of piperacillin/tazobactam 4.5 g IV and tobramycin 500 mg IV as one-time doses for her suspected urinary tract infection (which you consider at this point to be urosepsis).
You Avoid Premature Closure
Yet to you, something does not seem right. Her overall presentation does not seem to add up in being secondary to urosepsis. Is there some other underlying issue that is taking place? In addition to the labs you have already ordered for our patient, you quickly decide to add a thyroid function panel, just in case.
Thyroid Storm and Endocrine Emergencies: Sepsis Mimics
Endocrinologic emergencies often fall at the wayside and are not generally considered as a possible diagnosis up front in patients in the emergency department who meet the criteria for systemic inflammatory response syndrome (SIRS). It becomes too easy to label them as "septic", and we may forget that endocrinologic emergencies, specifically thyroid storm, can present in very much the same way. To me, it really is the missed mimic of several disease states, as described above in our possibly uroseptic patient.
Diagnosis of thyroid storm can be somewhat of a challenge because of this, but a scoring system developed by Burch and Wartofsky 1 can assist in determining the likelihood of thyroid storm in patients based on presenting signs and symptoms. A previous ALiEM blog post further discusses some of the nuances associated with the diagnosis of thyroid storm.
In the case of our patient above, both laboratory parameters and the overall clinical picture confirm our suspicion of thyroid storm. The question is now —
How do we treat thyroid storm? 3B's of Thyroid Storm "Soccer"
You can think of the mainstay treatment strategies of thyroid storm based on three main goals (what I like to call the 3 B's of thyroid storm soccer):
- Block the production and release of thyroid hormone (preventing the opposing team from getting the ball and scoring)
- Block the sympathetic outflow (preventing the soccer ball from going out of bounds)
- Block peripheral conversion of T4 to T3 (preventing penalty kicks)
Specific Therapeutic Agents
The agents are discussed below along with some EM pharmacy pearls that may be beneficial to those of you practicing in the emergency department.
1. Thionamides
- Mechanism of action: Inhibit thyroid peroxidase, an enzyme involved in the production of T3 and T4 through the iodination of tyrosine residues on thyroglobulin
- Agents: propylthiouriacil (PTU) and methimazole (MMI)
- Dosing
- Loading dose: 600 to 1000 mg PO
- Maintenance dose: 200 to 250 mg PO q4h
- Loading dose: 20 to 25 mg
- Maintenance dose: 20 to 25 mg PO q4h
- No head-to-head trials have shown any benefit of using one thionamide over another in the management of thyroid storm
- Additional benefit of PTU in thyroid storm:
- Inhibition of the peripheral conversion of T4 to T3 (3rd "B")
- Alternative routes of administration:
- PTU and MMI can both be administered through the rectal route as a suppository and retention enema
- Shown to have good response in several trials 2–4
- Intravenous (IV) thionamides are currently not commercially available in the United States
- IV formulation of MMI is available in Europe
- Success reported in case reports and case series of treating thyroid storm with IV MMI compounded formulations 5,6
- PTU and MMI can both be administered through the rectal route as a suppository and retention enema
- Pregnancy considerations:
- PTU is generally preferred over MMI
- Adverse effects:
- PTU: black box warning for severe and/or life-threatening hepatotoxicity issued by FDA in 2010
- Agranulocytosis:
- Can occur at any point during treatment
- Tends to be dose-related with MMI, unlike PTU
- Granulocyte colony-stimulating factors (G-CSFs) can be used in the management of thionamide-induced agranulocytosis
2. Inorganic iodine
- Used to prevent the release of pre-formed thyroid hormone from the thyroid gland
- Various formulations:
- Saturated solution of potassium iodide (SSKI): 5 drops PO, NG, or PR q6h
- Lugol's solution: 8 drops PO, NG, or PR q6h
- Sodium iodide: 500 mg IV q12h
- Administration of inorganic iodine should be delayed for at least one hour after initiation of thionamide therapy
- Iodine load can serve as a substrate for thyroid hormone synthesis and exacerbate thyroid storm
- Iodine content of formations (NOTE: Solutions are not interchangeable.)
|Iodine Solution
|Content of Iodine Per Drop*
|38 mg iodine
|Lugol's Solution
|8 mg iodine
|* Based on 20 drops per mL
- The dose is by the dropperful (as opposed to mL) of solution
- Dissolve the dose in solution of 3 to 4 ounces of milk, fruit juice, or water to ensure that the full dose is given and to mask the bitter taste
- If true allergy to iodine or contraindication to iodine therapy (e.g. amiodarone-induced thyrotoxicosis):
- Consider administration of lithium carbonate 300 mg PO or NG q6h
- Maintain lithium level within range of 0.8 to 1.2 mEq/L
3. Beta blockade
- Enhanced α- and β-adrenergic stimulation in the setting of thyroid storm leads to clinical manifestations
- Propranolol: most commonly used agent
- Inhibits peripheral conversion of T4 to T3 (3nd "B")
- Effect not demonstrated considerably with other β-antagonists
- Blocks non-selective β-adrenergic receptors to allow for effective treatment of systemic effects, such as tremor, tachycardia, agitation, fever, diaphoresis, psychosis (2nd "B")
- Dose: 60 to 80 mg PO q4h
- Proper dosing of propranolol is essential because of dose-dependent effects on inhibition of peripheral conversion of thyroid hormone (> 160 mg/day), and rapid metabolism of the agent in the setting of thyroid storm
- Alternative route of propranolol: IV formulation (determine availability at your institution)
- Two-step method for administration:
- Test dose: 0.5 to 1 mg as slow IV push administered over 10 minutes
- Subsequent doses: 1 to 3 mg IV over 10 to 15 minutes every few hours to desired effect with monitoring of cardiac rhythm
- Inhibits peripheral conversion of T4 to T3 (3nd "B")
- Esmolol can be considered as an alternative agent
- Contraindications to beta blockade: guanethidine or reserpine with close monitoring for hypotension
4. Corticosteroids
- Depression of the hypothalamic-pituitary axis commonly occurs in the setting of thyroid storm
- Additional benefit: inhibition of peripheral conversion of T4 to T3 (3rd "B")
- Hydrocortisone: loading dose of 300 mg IV followed by maintenance dose of 100 mg IV q8h (or dose equivalent)
5. Other Therapies
- Cholestyramine resin:
- Can be used to interrupt enterohepatic recirculation of thyroid hormone, leading to decreased circulating levels of thyroid hormone 7,8
- Dose: 4 g PO q6h
- Supportive measures
- Fluid resuscitation
- Dissipation of heat with various cooling modalities for hyperthermia control
- Benzodiazepines for control of agitation and to minimize sympathetic outflow
Additional Reading
Tenner AG, Halvorson KM. Endocrine causes of dangerous Fever. Emerg Med Clin North Am. 2013 Nov;31(4):969-86. PMID: 24176474.
Expert Peer Review
As a follow up to Nadia's excellent review of the treatment options for thyroid storm there are a few points not to miss when managing a patient with thyroid storm:
1. Thyrotoxicosis is a life-threatening emergency with a clinical diagnosis.
The diagnosis of thyrotoxicosis can be subtle and will absolutely be missed by the clinician who has not considered it on his or her differential. Yes, labs may confirm our suspicions, but, just like any other severely ill or unstable patient in the ED, we cannot wait for the results before starting treatment. Thyroid storm carries a mortality of 20-30%, and treatment should be started once it is reasonably suspected. The Burch-Wartofsky score, as mentioned in the article, is a helpful clinical tool that is based on the presence of fever, tachycardia, signs of CHF, atrial fibrillation, CNS dysfunction, GI dysfunction, and presence or absence of a precipitating event—all assessments that can be made at the bedside. This patient's score would be 60, and scores above 45 are highly suggestive of thyroid storm.
2. Wait at least one hour after PTU/MMI administration before giving iodine.
Another key point in Nadia's review is that order of administration of some of the medications is important. As she stated, iodine can actually exacerbate storm; thus administration of iodine should be at least one hour after PTU/MMI in order to ensure adequate inhibition of hormone synthesis.
3. Antipyretics often will not work, and salicylates should be avoided.
Remember that the "fever" of thyroid storm is thought to be primarily due to an increased metabolic rate (rather than pyrogen production with an increased hypothalamic set point seen in infections). Thus antipyretics like acetaminophen and ibuprofen are not likely to reduce core body temperature, and salicylates can actually exacerbate thyroid storm by increasing levels of free thyroid hormone and should be avoided.
4. All patients with storm should have a full infectious work-up with a low threshold for antibiotic administration, as well as evaluation for other physiologic stressors.
While the "fever" may be due to increased metabolism, remember that any physiologic stressor can be the precipitating event that sends the hyperthyroid patient into thyroid storm. It is extremely important to look for that stressor (i.e. infection, ischemia, pregnancy) and, as was the case with this patient, all patients with storm should have a full infectious evaluation with a low threshold for treating with antibiotics.
5. These patients should have ICU and Endocrine involved early.
Given the mortality rate cited above, while you are initiating treatment and sending labs for confirmation and follow-up, be sure to involve your endocrine and ICU colleagues early to minimize treatment interruptions, provide for a more facile transition of care, and maximize the patient's chance of survival.


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The Growth of Christianity
The development of Christianity
There are three main related factors that brought about the increase and increase of Christianity, and ultimately its success. We were holding a mixture of political, social and economic factors. The increase of early Christianity may be the main topics much debate and historical analyses. I am trying to simply outline and reply to a number of the main social factors that cause the growth of Christianity. lineage of mary
Christianity have come in the perfect time, toy trucks where life was uncertain and several circumstances cannot be controlled like the barbarians invading; fires home whole cities and plagues killing off quite a lot of people, regardless of whether you were rich or poor it made no difference, life within the Greco-Roman world was very fragile and short. Life-span was not great and the person with average skills lived until round the age of 30 or even much less. Life-span was minimal along with what could possibly have appealed to pagans could be that the Christian religion and doctrines offered hope and certainty from the afterlife and also some personal divine protection nowadays. These new doctrines could have seemed attractive to pagans, when there was clearly growing discontent with pagan practices and a general spiritual unrest. Like Christianity the Roman Religion was to the ordinary man but interest was waning along with the mystery religions were much too complicated for your common Roman, thus the people's choice was likely to be Christianity.
Christianity also offered desire to a usually pessimistic society that considered that their destinies were fixed, with the idea to maintain the Gods' favour or be out of it, without having hope of redemption. Christianity offered an alternate together with the much desired potential for salvation.
Christianity was primarily a metropolitan movement, during these urban centre's Christianity grew at the steady pace, the towns of cities including Antioch, were very condensed with individuals it is estimated that there are 117 people per acre. When compared with modern cities today this can be rather overcrowded. The overcrowding was very extreme, entire families existed together in single room apartments; this left little personal space and allowed everyone to learn each other's business. Considering that urban centre's were dramatically overcrowded understanding that early Roman Greco cities had minimal sanitation or sewerage to the average apartments people would often just throw their bodily waste out the window with their apartments to the streets. Starks describe the problem over these urbanized areas as:
Given limited water and means of sanitation and also the incredible density of humans and animals, a lot of people in the Greco-Roman world would have lived in filth beyond our imagining.
Apartments were often Smokey, dark, damp and try to dirty. The air was filled up with the aroma of sweat, urine and faces. Onto of those conditions the rodents and bugs were everywhere of these apartments. The location streets just weren't far better they had open sewers, animal manure and crowds from time to time it absolutely was so bad there are dead human corpses abandoned in the streets. When cities were within a constant condition of filth, insects and crowding, disease was rife of these conditions, especially when these Roman societies did not have any antibiotics or understanding of germs. Often plagues would strike and physical illness was most likely an integral part of lifestyle. A good example of this was case study of human faeces which were seen in a cesspit in Jerusalem showed a lot of tapeworm and whipworm eggs, which shows poor sanitary conditions where humans often arrived to exposure to human faeces.
Christianity revitalized the way of life in Greco-Roman society offering social change, which managed some of the consequences of urban problems. Charity and hope was wanted to homeless along with the poor, some of the cities were filled with newcomers and strangers and Christianity offered a prolonged family and a base for attachments along with effective nursing services in times of disaster, that were often due to plagues, earthquakes and fires.
Christianity's attitude towards society and it is social impact greatly triggered the development and success in the church. The church was particularly well-known for the acts of charity, chances are how the charity itself was probably the most influencing factors for the growth of Christianity.
The church offered this charity to every one, including pagans and Jews. Through the third century the Church was taking care of 1,000 400 widows short of funds. The church itself was rich and as outlined by Eusebius, by the year 251 the church in Rome supported the bishop, 46 presbyters, 7 deacons, 7 sub deacons, 42 acolytes and 52 exorcists, reader and doorkeepers, but also over 1500 widows and needy persons. The churches obvious financial stability leads so that it is popular and it successfully expanded given it helped those involved with need, it offered help and quite often people were changed into Christianity as a result of the kindness and a focus they received. Although the Roman Empire did have some charitable services like the bread dole, Christian charity far outweighed the state's charity.
Throughout the first century on the fourth century there were government enforced persecution of early Christianity, though not constantly. Persecution and martyrdom has been a indication of the effectiveness of Christianity, which in turn shows when the movement was attracting attention from your Roman state. Such emperors that instigated severe persecution were Decius and Diocletian. There have been sufficient levels of Christians in North Africa for martyrdoms to become noticed, one of these simple martyrdoms were Perpetua and her slave girl, Felicity who have been thrown to the lions following a trial.
Tertullian wrote that "the blood of Christians is seed" which is often misquoted as "the blood with the martyrs will be the seed of the church." Tertullian may have been saying this while he belief that martyrdoms created new converts or might have strengthened the church.
The Roman Empire wished to exterminate this new religion immediately and yes it seems it tried at first to exterminate every Christian they may find but later under Decius they started new techniques to try to exterminate Christianity one of many ways was by taking out the clergy and the bishops as well as extracting lands and churches from the Christians, inspite of rank while forcing these to sacrifice for the states pagan gods or perhaps be punished severely with torture, exile, slavery and quite often execution, depending on numerous reasons along with the use of persecution.
This might experienced to provide this new religion much publicity, in particular when it had been in the circus arenas being killed by wild beats might have been creating attention, this indicates many might have seen these peculiar people willing to suffer excruciating torture and also die for their God and religion, this should have left the pagan with something further to consider and consider when they were ready to die for pagan gods.
The Christians might even have won converts in some areas, for their courage in the persecutions, the effectiveness of their faith and the support they showed one another, Tertullian said that pagans had exclaimed within the arenas during martyrdoms "See how these Christians love one another" this indicated the social nature in the Christian faith. The persecutions also created apologists these folks were those who would be writing looking to convince the police that they done nothing wrong, get the job done Emperors read these long letters of apology nobody knows, it appears rather unlikely however one could suggest State officials having read these letters of apology.
Another part of Christian growth was that Christianity as well as friendships formed from within the Church bring about its successful growth because people that became a Christian felt they were to fulfil the truly amazing commission as taught by Jesus and also the apostles plus they could pass the material onto their friends, this in many cases led to an end knit community which was appealing in an era if it was expected individuals to take care of yourself. Within this Greco-Roman era religious and self confidence was quite definitely interlinked. It absolutely was taught within the church that if Christian travellers originated outside the city or were strangers to an alternative city, Christians could provide their needs and provide shelter to these Christians, this is not merely taught inside the teachings of Jesus but additionally by the apostle Paul. Therefore it was a motivation becoming a Christian as there was always help and internet sites which could you inside a large empire. It turned out as an extended family wheresoever you went within the Roman Empire. Eusebius writes how the Christian missionaries were so inspired by the Holy Spirit they saw mass conversions occur, it can possibly be a contributing factor.
Christianity also gained some favour in society due to the improvement within the treating women, plus it elevation of their social status. Christianity taught that marital unfaithfulness a single partner as serious such as another understanding that in in accordance with the New Testament, husbands should treat their wives basic consideration and love as Christ manifested for his Church, though women remained as considered homemakers and wives. It's believed that Christianity made its distance to the aristocracy in Rome at the time with the influence of their wives.
The Greco-Roman world was quite different woman had much less expensive rights than men. It had been a very male orientated society where male babies were wanted and feminine babies rejected this ended in infant side of female babies. Some excavations have realized hundreds of babies bones within an underground sewer regarded as female babies. It had not been uncommon that women were offered in marriage before that they had reached puberty to more aged men as well as the cultural custom was that the women were the house of the man, either the father or perhaps the husband. Women played a major role in the early Christian church this will likely happen to be simply because they received more rights within the Christian community when compared with women inside the Greco-Roman world. We view in most early writings in regards to the persecution of Christians a large number of more females clothing were stored or found than men's, greater than double, this might suggest there were much more females than males noisy . church.
If it is true that there have been a lot more females than males in early church then that permits for most secondary conversions. Secondary conversions are those which might be a result of another individual being converted because of the first conversion, for instance a woman is converted then again shortly after her husband is converted which more than likely do not need occurred in the event the woman has not been originally converted. Christian doctrines were against abortion and infanticide. This may also have some relation to the birth-rates of Christian woman compared to their pagan counterparts.
The spread of Christianity also involved Christian writings by the end of the initial century the writings of Paul and also the apostles of Jesus have been spread sporadically over the Roman Empire. Apart for the early apostolic writers, others go about advocating, defending and propagating Christianity. Justin Martyr who lived around Ad 100-160 was obviously a Christian teacher and philosopher, he wrote the foremost and second apology. There have been many subsequent Christian writers throghought early years of the church, frequently we were holding well-educated, for example Origen, Tertullian and many more. In the pagan mystery religions merely the elite could browse the sacred and secret texts, in Christianity often the Gospels and Paul's epistles were read out aloud for those to know in the church, this will likely have drawn the pagans when contemplating a selection in further religious observance. The Christian writings also acted as a way of spreading the Gospel message around, often reaching further than the Roman Empire itself.
Overall there are many factors that caused the prosperity of the church. The caring for widows, the indegent as well as the sick, the Christians attitudes to death, when dealing with martyrdom, better equality among males and females as well as the treatments for slaves, all this made a direct impact on society were these products were rare. Christianity was less likely to succeed by any ordinary standard of expectation nevertheless it did from the Christian use of charity and it is simple guide to salvation. We can't say or point out one cause and voice it out was the sole reason why Christianity would have been a successful religion; the causes mentioned develop a substantial cumulative case to the rise of Christianity. lineage of mary

subset: commoncrawl


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In a sense, Ulman Dark could return life to the dead. It was a risky proposition, though. Risky in the sense that it rarely worked as expected…if it worked at all. The cost had to be paid up front, just in case worse turned to worst.
Hel Hold's latest "crop" returned to Zelkor's Ferry carrying both parts of Ben. None knew if both parts would be required by the necromancer, should he be able to perform some miraculous cure. It seemed prudent to bring both parts, if only in that Ben probably wanted them together in death as in life.
Ulman advised against a resurrection, citing the poor probability of success and the rather mundane result of raising a dead thing back to a living thing. He noted that it would be more interesting to attempt to create a deader thing from the dead. Something with a bit more power and some nice dangling rotted flesh.
The crop decided against the advice, and straws were drawn to see who would have to donate living tissue and blood to aid in the coming ritual. Well, not exactly straws. Everyone who could invest gold, silver or gems got to keep their blood. Barak, the penniless, got to donate.
Days passed, and Ben began to really put a stink on. Barak looked wane from the daily leechings, transfusions, and ingestions of gag-inducing concoctions. On the day everyone believed was the last that Barak could endure, Ben's eyes fluttered open.
Ulman was grieved, even as the party cheered his success. As a necromancer of some great capability, he sensed that something was missing from Ben. An examination revealed that Ben's soul was missing. Ulman was not surprised, as he had long believed that those who died in and around Zelkor's Ferry were cursed to have their souls stolen away by the old ruin near the Mouth of Doom.
Suspenseful music seemed to suddenly fill the air as Ulman explained that a nearby ruin once served as the secret exit from a Temple dedicated to Orcus. The priests there had grown wilder and more dangerous to the surrounding lands until the Jarl was forced to deal with them. A band of heroes endowed with the light of the divine was tasked to bring down the evil temple.
They slew every remaining priest in that place, and destroyed every reminder of its wickedness. But, in their fervor to rid themselves of the unholy worshippers, they left behind the high-priest's symbolic token to his ghastly god, Orcus. Ulman recounted how he believed the rod still existed, there in the Temple ruins. The rod, he said, was surrounded by the bones of the dead priests and drew the escaping souls of those killed in the local area to itself. A soul so drawn was trapped in the chamber of the priests and could not travel to its ultimate destination.
Ulman then told you that Ben's soul was trapped in that ruin. It could be rescued, though. All you had to do was enter the probably abandoned sinister dark hole in the earth and ferret out a room full of skeletons hiding the almost certainly very deadly rod of Orcus.
Easy-peasy, lemon squeezy.


text:
Waverly Kids
WK Ipanema Striped Dec
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A common evolutionary origin for mitochondria and hydrogenosomes
Trichomonads are among the earliest eukaryotes to diverge from the main line of eukaryotic descent. Keeping with their ancient nature, these facultative anaerobic protists lack two "hallmark" organelles found in most eukaryotes: mitochondria and peroxisomes. Trichomonads do, however, contain an unusual organelle involved in carbohydrate metabolism called the hydrogenosome. Like mitochondria, hydrogenosomes are double-membrane bounded organelles that produce ATP using pyruvate as the primary substrate. Hydrogenosomes are, however, markedly different from mitochondria as they lack DNA, cytochromes and the citric acid cycle. Instead, they contain enzymes typically found in anaerobic bacteria and are capable of producing molecular hydrogen. We show here that hydrogenosomes contain heat shock proteins, Hsp70, Hsp60, and Hsp10, with signature sequences that are conserved only in mitochondrial and alpha-Gram-negative purple bacterial Hsps. Biochemical analysis of hydrogenosomal Hsp60 shows that the mature protein isolated from the organelle lacks a short, N-terminal sequence, similar to that observed for most nuclear-encoded mitochondrial matrix proteins. Moreover, phylogenetic analyses of hydrogenosomal Hsp70, Hsp60, and Hsp10 show that these proteins branch within a monophyletic group composed exclusively of mitochondrial homologues. These data establish that mitochondria and hydrogenosomes have a common eubacterial ancestor and imply that the earliest-branching eukaryotes contained the endosymbiont that gave rise to mitochondria in higher eukaryotes.
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Handcrafted Ear Wires
Its fairly straightforward to make your own ear wires for earrings.
To start you will need.
- Wire - I use a 0.6mm diameter wire.
- Side Cutters
- Round nosed pliers
- Something round to shape the ear wires. I use the handle of my wire rounder but any round object such as a pen will do.
- Flat nosed pliers
Start by using the side cutters to cut two lengths of wire approx 6cm long.
Using the round nosed pliers create a small loop on one end of the wires.
Shape the wires over the round object. i usually start about half a centimetre from loop.
Using the flat nosed pliers, bend the wire by the hook forward.
On the other end, bend the wire back.
Hammer the front part of the loop to flatten it, this helps to harden the wire and keep its shape.
For the finishing touches file the end of the wire so that its smooth.
For variation, small Beads or Crystals can be added to the area by the hook or wire wrapped around it.