Fever of unknown origin

Disease class: Fever

Also known as

• FUO
• Pyrexia of unknown origin

Fever

Also known as

• Pyrexia
• Febrile response

 

Subtypes

• Fever of unknown origin

History of radiation injuries

This post chronicles significant incidents of radiation-induced injury.
It was inspired by the high quality new miniseries Chernobyl, produced by HBO.

 

Please refer to:

• Ionising radiation
• Radiation injuries

 

Timeline

• 1903: Marie and Pierre Curie won the Nobel Prize for their research into radiation. Pierre Curie died of a head injury in 1906. In 1934, Marie Curie died of radiation-induced aplastic anaemia.
• 1945: 18 USA citizens were injected with plutonium in a series of experiments without informed consent. They were selected because they had diagnosed terminal illnesses. Each died of their original illness.
• Albert Stevens was injected with 131 kBq plutonium.
• He was never diagnosed with any radiation injuries. He died of apparently unrelated heart failure 21 years later, in 1966, aged 79
• The total dose emitted was 64 Sv, by his time of death.
• The doctor who led the human plutonium experiments, Dr. Joseph Gilbert Hamilton, died of radiation-induced leukaemia in 1957, aged 49.
• 1945: After the atomic bombing of Hiroshima and Nagasaki by the USA, there were 129,000–226,000 estimated casualties.
• Within the first few months, 90,000-166,000 people died in Hiroshima, 60,000-80,000 died in Nagasaki. 
• Early deaths and injuries occured as a result of the explosion itself and ARS. 
• 1978: Russian scientist Anatoli Bugorski was shot in the head by a high energy proton beam. He received a dose of over 8 Sv and the high energy beam burnt a narrow hole through his head. He survived the incident and recovered with minor disabilities. He went on to complete his PhD and he is currently still alive at 77 years old.
• 1986: The disaster at the Chernobyl Nuclear Power Plant, in Pripyat, Ukraine. 
• There was an explosion which breached the core. The ongoing fission reaction maintained open fires for days, which propelled large quantities of highly radioactive materials (including the radioisotope iodine-131) into the atmosphere. The enviroment and local ecosystems were heavily contaminated by these materials.
• Radiation level estimates were over 20,160 roentgens per hour in some areas. This is equivalent to 0.056 Sieverts per second. After 18 seconds the absorbed dose would be over 1 Sv, high enough to cause ARS in a typical patient. After 90 seconds, the absorbed dose would be over 5 Sv, high enough to cause fatal ARS in a typical patient.
• Some servicemen worked in these contaminated areas for many hours.
• 237 of the most exposed individuals developed ARS, of whom 31 died within 3 months. A further 15 later developed fatal thyroid cancer.
• These patients were contaminated with strongly radioactive materials. Their bodies were emitting ionising radiation at typical doses of around 6 Sv per hour.
• The current European death toll from the incident is estimated between 9,000-16,000. 
• It is predicted that the final toll from the disaster will include 41,000 cancer cases and 4,000 cancer deaths.
• 1990: The radiotherapy accident in Zaragoza, Spain. 
• Patients were treated with an unsafe radiotherapy device. 
• This caused 27 cases of ARS and 11 deaths.
• September 1999: The Tokaimura nuclear accident in Ibaraki, Japan.
• 3 technicians were exposed to high doses of radiation. 
• Hisashi Ouchi received a dose of 17 Sv. He developed ARS and aplastic anaemia. None of his chromosomes could be identified by karyotyping. His white blood cell count was 0. Despite this, he was aggressively treated and resuscitated many times. He lived for 83 days and died in December 1999.
• Masato Shinohara received a dose of 10 Sv. He developed ARS and aplastic anaemia. He received skin grafts. He lived for 7 months and died of in April 2000, from an infection.
• Yutaka Yokokawa received a dose of 3 Sv. He developed ARS and remained in a hospital for 3 months. He is not known to have died.
• The former 2 cases are ethically controversial, because both patients were exposed to lethal doses of radiation, with no chance of recovery. Every effort was made to keep them alive, so their suffering was prolonged. It is unclear whether there was a failure in medical decision making or a utilitarian desire to research the biological effects of severe irradiation.
• November 2006: The poisoning of Alexander Litvinenko in London, UK. 
• On the 1st November 2006, Litvinenko met two former Russian espionage agents. Later that day he developed ARS. Investigations revealed that his body was contaminated with the radioisotope polonium-210. It has been speculated that the radioisotope was sprayed into his teapot by an assassin.
• The estimated initial activity of the ingested material was 4.4Gbq.
• The dose equivalent in his organs was estimated between 20 Gy (alpha radiation) - 100 Gy (alpha radiation). This is equivalent to a dose between 400 Sv - 2000 Sv.
• Litvinenko died on the 23rd of November 2006.

Ionising radiation

Fundemental science article

Also known as

• Commonly called "radiation"
  

Physics

The structure of matter

• Matter is made of atoms, ions and electrons.
• Every atom has a central component called a nucleus. The nucleus is orbited by electrons. 
• The nucleus is made of protons and neutrons. The number of protons in an atom is equal to the number of electrons. The number of protons is known as the atomic number.
• The number of protons and neutrons together is known as the mass number.
• Each proton and neutron is comprised of subatomic particles called quarks.
• One of the fundemental interactions of the universe is known as the 'strong interaction'. It is responsible for binding together neutrons and protons in the atomic nucleus. This interaction occurs as an ongoing quark exchange between protons and neutrons. 
• As the proton number gets higher, the neutron number usually rises too.
• If there is a gain of an electron without a gain of a proton, an atom becomes a negative ion. 
• If there is a loss of an electron without the loss of a proton, an atom becomes a positive ion.
• Each element has a specific number of protons. Different atoms of the same element can have a different neutron number. These are known as isotopes of that element.
• Some elements and isotopes are very unstable systems. Generally, the higher the mass number, the more unstable the atom is.

Nuclear decay, radioactivity

• One of the fundemental interactions of the universe is known as the 'weak interaction'.
• Through this interaction, atomic nuclei can decay to a more stable state, producing a new element or a new isotope.
• Nuclear decay events result in the expulsion of alpha particles (high-energy helium-4 nuclei), beta particles (high-energy electrons), positrons (anti-electrons) or gamma rays (high-energy photons). The new isotope produced by the decay is more stable.
• Positrons interact with electrons in a process called annihilation. Both particles are destroyed but due to mass-energy conservation, symmetrical gamma rays (high-energy photons) are emitted.
• Radioisotopes undergo nuclear decay at perfectly regular intervals. This is the principle behind atomic clocks.
• The half-life of an isotope X is that amount of time that it will take for 100kg of isotope X to decay to 50kg of isotope X. The half-life remains constant for an isotope, but the emitted dose of radiation decays exponentially with time. The half-lives of some radioisotopes are billions of years.
• Alpha particles, beta particles, and gamma rays are highly energetic and ionising.  
• Ionising radiation can turn atoms into ions. This can disrupt the chemical bonds of any molecule.
• As air becomes ionised, there may be a metallic taste, a smell of ozone, or an ionised-air glow.
• Ionisation events can be detected by instruments such as the Geiger–Müller counter. These instruments display a count per second.

Activity

• Activity of a radioactivity material can be expressed as Bq (Becquerel). 1 Bq is equivalent to 1 nuclear decay per second. The greater the mass of the material, the greater the measured activity.
• The mass of radioactive material and the activity fall as the material decays.
• A material with a half-life of 100 years will have decayed to half the mass of that radioisotope after 100 years.
• Due to long half-lives and large amounts of contamination, some areas on the planet will continue to emit significant amounts of ionising radiation for thousands of years. They must remain isolated and contained to prevent future disease.

 

Doses

• When measuring ionising radiation dose, the Sievert value reflects the energy (in joules) transferred to 1kg of matter each second.
• 1 Sv = 1000 mSv.
• Approximately 1 gray per second (if gamma radiation).
• Approximately 100 rem per second.
• Approximately 100 rad per second (if gamma radiation).
• Approximately 360,000 roentgen per hour.
• Approximately 1 watt per kilogram.
• Approximately 1 joule per kilogram per second.
• The average person in the USA receives an estimated effective dose of about 3 mSv (milliSievert) per year from background (natural) radiation.
• A dose of 4-5 Sieverts or more, absorbed within a short time period, causes death in 50% of patients, within 30 days.

 

Sources of ionising radiation

Mild 

• Electronic devices
• Cosmic rays
• Natural radon gas stores

Moderate

• Radiological imaging
• Radiotherapy devices
• Brachytherapy
• Solar radiation (sunlight)

Severe

• Waste from nuclear power plants
• Use of nuclear weapons

 

Pathophysiology

• High energy ionising radiation causes damage to all exposed biological structures.
• The energy of the radiation can result in tissue damage similar to thermal or electrical burns. A sufficiently high dose will vaporise living tissue.
• The most radiation-sensitive structures within cells are the genetic materials. DNA and RNA are easily damaged or destroyed, leaving the cells incapable of functional protein synthesis.
• Successful mitosis cannot occur so destroyed cells are not replaced.
• The cell cannot repair physical damage.
• Many cells undergo apoptosis (programmed cell death).
• Tissues start to break apart.
• Any DNA damage can persist in the long-term to cause future cell dysfunction including malignant transformation.

Exposure to ionising radiation can cause:

• Acute radiation syndrome (ARS) 
• Radiation injuries
• Abortion (if pregnant)
• Birth defects (if pregnant)
• Malignancy
• Aplastic anaemia

 

Prevention of disease

• Use of a Geiger–Müller counter: Each count represents one ionisation event (i.e. one expulsion of an ionising ray or particle). These can be heard as audible clicks.
• Use of protective clothing and shielding. Lead is a useful material for absorbing ionising radiation.
• Exposure to radioactive contaminants could cause ARS, pregnancy abortions and it increases the risk of developing cancer. For this reason:
• Any fabrics, animals, crops or fluids exposed to radioactive materials must be safely identified, gathered, destroyed and contained.
• Any individuals exposed to radioactive materials must be quarantined. Contaminated corpses must be buried in coffins designed to safely contain them.
• Heavily contaminated areas must be evacuated.

 

History of radiation injuries

Radiation-induced leukaemia

Disease class: Leukaemia

Disease class: Radiation injuries

See also

• Acute radiation syndrome
• History of radiation injuries

Smouldering Multiple Myeloma

Disease class: Hypergammaglobulinaemia
Disease class: Paraproteinaemias
Disease class: Precancerous conditions

This refers to a plasma cell dyscrasia, in which abnormal excessive levels of gamma globulins are detected in the blood. There are no symptoms, but the patient has an increased risk of progression to multiple myeloma.

Monoclonal gammopathies

• Monoclonal Gammopathy of Undetermined Significance 
• Smouldering multiple myeloma
• Multiple myeloma

Heavy chain disease

Disease class: Lymphoproliferative disorders
Disease class: Paraproteinaemias

DNA repair-deficiency disorders

Disease class: Metabolic diseases

POEMS syndrome

Disease class: Paraproteinaemias

Also known as

• Osteosclerotic myeloma
• Crow–Fukase syndrome
• Takatsuki disease
• PEP syndrome

 

Etymology

• Polyneuropathy
• Organomegaly
• Endocrinopathy
• Myeloma protein
• Skin changes

• Polyneuropathy
• Endocrinopathy
• Plasma cell dyscrasia

Monoclonal Gammopathy of Undetermined Significance

Disease class: Hypergammaglobulinaemia
Disease class: Paraproteinaemias

Also known as

• MGUS

This refers to a plasma cell dyscrasia, in which abnormal excessive levels of gamma globulins are detected in the blood. There are no symptoms, but the patient has an increased risk of progression to malignancies such as multiple myeloma. One study found that the risk of progression to malignancy was 11% (6.5 times higher than the general population).

 

Monoclonal gammopathies

• Monoclonal Gammopathy of Undetermined Significance  
• Smouldering multiple myeloma
• Multiple myeloma

Paraproteinaemias

Disease class: Blood protein disorders
Disease class: Immunoproliferative disorders 

Types

• Cryoglobulinaemia
• Heavy chain disease 
• Immunoglobulin light-chain amyloidosis
• Monoclonal Gammopathy of Undetermined Significance 
• Multiple myeloma
• POEMS syndrome
• Smouldering multiple myeloma
• Waldenstrom macroglobulinaemia

Cysts

Disease class: Neoplasms

 

Hamartoma

Disease class: Neoplasms

Leukoplakia

Disease class: Precancerous conditions

Definition

White plaques of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer.

 

Features

• Firmly attached to an underlying mucous membrane. 
• Associated with a significant risk of malignant transformation.
• White or grey coloured.
• Flat.

 

Etymology

• leuko- = white
• -plakia  = plate  

 

Risk factors

• Tobacco smoking  
• Excessive alcohol consumption
• HIV infection / AIDS

Cavernous haemangioma

Disease class: Haemostatic disorders

[Oncology] Introduction

Oncologists specialise in diseases caused by cancer. Cancer has a more accurate name: malignant neoplasm.
There is significant overlap with many specialties.
Palliative care medicine is strongly associated with oncology due to the dire prognosis of many malignancies and the slow course of cancer.

 

Etymology

Ancient Greek ὄγκος (ónkos) = lump, mass, bulk
Ancient Greek λογία (logia) = study

Ancient Greek νέος (néos) = new, young
Ancient Greek πλάσμα (plásma) = formation

 

Subspecialties

Most oncologists are subspecialised in one management discipline:

• Medical oncology : use chemotherapy, hormone therapy and biological agents (systemic treatments).
• Clinical oncology (sometimes called radiation oncology) : undergo radiology training. They can use radiotherapy and systemic treatments.
• Surgical oncology : surgeons subspecialised in oncology.

Senior oncologists usually maintain 1, 2 or (rarely) 3 site specialties. This means that they prioritise learning about these sites and preferentially manage patients with a malignancy of these sites. This happens because optimal practice in oncology changes rapidly. It would be impossible to maintain satisfactory knowledge in more than 3 systems. Examples of site specialty pairings:

• Thoracic malignancies and skin cancers
• Lung cancer and urological malignancies
• CNS malignancies and prostate cancer

 

Hybrid specialties

• Paediatric oncology
• Haemo-oncology
• Neuro-oncology 

Modern oncology usually involves a multidisciplinary team. This includes physicians from:

• Radiology
• Pathology 
• Paediatrics (when appropriate) 

Often these physicians will have subspecialised in oncology or develop a special interest in it. 

 

History taking 

 

General pathophysiology of cancer

 

Management principles

 

Cancer incidence for common cancers

 

Other diseases:

• Paraneoplastic syndromes
• Adrenal cancer
• Phaeochromocytoma 
• Sarcoma
• Osteosarcoma
• Chondrosarcoma

Osteitis

Disease class: Bone diseases

 

Immune reconstitution inflammatory syndrome

Disease class: Immune system diseases

Immunoproliferative disorders

Disease class: Immune system diseases

Types

• Hypergammaglobulinaemia 
• Lymphoproliferative disorders 
• Paraproteinemias 

Secondary hypertrophic osteoarthropathy

Disease class: Joint diseases

Causes

• Chronic lung diseases