Progeria (Hutchinson-Gilford syndrome)

Progeria is a disease which the body’s natural aging process is dramatically accelerated.

Prevalence: 1 in 8 million babies are born with this condition.

Genetics: The disease is genetic, however it occurs as a sporadic new mutation and is not usually inherited.

Progeria is caused by a point mutation where Cytosine is substituted for Thymine creating an unusable type of protein called Lamin A.

Lamin A is part of the building blocks of the nuclear envelope. This results in abnormal cellular morphology.

Treatment:

No treatments are yet effective.

Clinical treatment trials with farnesyltransferase inhibitors (FTIs), a type of anticancer drug, began early last year.

Brown, W. Ted; Berglund, Peter;  Boehnke, Michael; Collins, Francis S.Csoka, Antonei B.; Dutra, Amalia; Durkin, Sandra; Erdos, Michael R.; Eriksson, Maria;  Glover, Thomas W.; Gordon, Leslie B.; Glynn, Michael W.; Moses, Tracy Y.; Pak, Evgenia; Scott, Laura; Singer, Joel; Robbins, Christiane M. Recurrent de novo point mutations in lamin A cause Hutchinson|[ndash]|Gilford progeria syndrome. 2003.  Nature, 423 (6937) :293-298.

3 types of vascular access ports used in hemodialysis

Hemodialysis refers to a method for cleaning the blood. Dialysis functions to removemetabloic waste products such as potassium, urea from the blood during renal failure. Additionally, dialysis may be used to remove other chemical toxins from the bloodstream in cases of overdose.

In the case of renal failure, patients may undergo dialysis treatments three times a week for 3 to 4 hours.

Hemodialysis requires a vascular access site. This is an arterial and venous site on your body from which your blood is removed and returned after it is filtered by the dialysis machine.

Three major forms of vascular access are used: 

• The native arteriovenous fistula

• The synthetic arteriovenous graft (expanded polytetrafluoroethylene)

• The cuffed, tunneled central venous catheter

  

Cheung, Alfred, K, Li, Li, Terry, Christi, M, and Shiu, Yan-Ting, E. 2008. Neointimal hyperplasia associated with synthetic hemodialysis grafts. Kidney International. 74 (10) 1247-1261.

Zoonosis

 Zoonosis refer to any infectious disease that is able to be transmitted (by a vector) from other animals, both wild and domestic, to humans.

 

Current human diseases and their wild animal origins

Disease	Wild Animal Source
Hepatitis B	Chimpanzees
Hepatitis A	Apes
Influenza A	Wild birds
Plague	Rodents
Dengue fever	Old World primates (lemurs)
East African sleeping sickness	Wild and domestic ruminants (cows etc)
Vivax malaria	Asian macaques
West African sleeping sickness	Wild and domestic ruminents
Yellow fever	African primates
Chagas` disease	Many wild and domestic mammals

Monitoring of wild animal diseases and close associted human activity may help prevent or intercept diseases before they become a global threat to humans.

Pandemic: an epidemic that is geographically widespread; occurring throughout a region or even throughout the world

Animal disease to human pathogen:

Steps and process through which a microbe endemic to animal populations is transmitteed to and becomes a human pthogen.

Stage 1:

• The pathogen is present in animals, yet remains undetected in humans under natural conditions.

• Pathogen endemic or epidemics contained within a perticular animal population or species

   

Stage 2:

• Animal pathogen has been transmitted to humans

• However, the disease is transmitted in one direction only

• The animal disease is not transmitted person to person

Stage 3:

• The animal pathogen now is capable of being transmitted person to person

• this person-person transimission of the disease causes and outbreak within the human population

• The resulting human epidemic is of short duration

• Disease rapidly dies out within the human popluation

 

Stage 4:

• Pathogen exists in animals (animal carriers)

• Pathogen undergoes a regular cycle of animal to human transimission

• Person-person transmission results in long duration outbreaks

• Disease persists cycling within the human population

 

Stage 5:

• Pathogen now reaches a persistent infection level in humans

• Pathogen has now evolved and strains have mutated to be specfic and exclusive to human beings.

 

Wolfe Nathan. 2009. Preventing the Next Pandemic. Scientific American. 300 (4) 76-81.

Swine Influenza

 

Swine Influenza is a respiratory disease that is carried by and infects pigs. Swine flu is type A influenza that regularly cause outbreaks of influenza among pigs. The classical swine flu virus (an influenza type A H1N1 virus) was first isolated from a pig in 1930.

Type A influenzas:

Type A influenzas are viruses from the Orthomyoxviridae genus. Type A influenza includes only a single species.

Swine flu:

Swine influenzas do not generally infect humans, however infections crossing to humans from infected pigs can occur.  Furthermore, it is known that human-human transmission of swine influenza can occur.

Flu viruses from an animal source (such as bird or pigs) have the potential to cause pandemics because they are generally so different from human viruses that people have little or no immunity to them. Animal flu viruses can make people sick when the perticular viral strain that typically infects only animals mutates and is then able to be transmitted to humans.

How people are infected with swine flu:

• Human infection with swine flu viruses are most likely to occur when people are in close proximity to infected pigs, such as in pig barns.
• Individals may also contract swine influenza from another person who is infected with the virus.

 

Current Swine infection statistics:

•  December 2005 through February 2009, a total of 12 human infections with swine influenza were reported from 10 states in the United States.
• Since March 2009, a number of confirmed human cases of a new strain of swine influenza A (H1N1) virus infection in California, Texas, and Mexico have been identified.
• Laboratories in Canada and the United States confirmed that large outbreaks of unusual respiratory illnesses in Mexico are caused by swine flu viruses closely related to those that infected eight people in California and Texas.

 

Symptoms of swine flu in humans:

• similar to the symptoms of regular human seasonal influenza
• fever
• lethargy
• lack of appetite
• coughing
• runny nose
• sore throat
• nausea
• vomiting
• diarrhea

Treatment:

Antiviral drugs therapy

1. amantadine
2. rimantadine
3. oseltamivir
4. zanamivir

 Swine Influenza antiviral drug resistance:

• The most recent seven swine flu viruses isolated from humans are resistant to amantadine and rimantadine.
• The CDC currently recommends oseltamivir or zanamivir for the treatment of swine influenza infection

U.S. Centers for Disease Control and Prevention.2009. Swine Flu. Retrived April 25, 2009 from http://www.cdc.gov/swineflu/

Hemoperfusion

Hemoperfusion is a chemical process used to remove drugs or toxic substances from an individual’s blood by passing it through a column of charcoal or other adsorbent material.

Hemoperfusion is often used as an effective method of drug removal from the blood stream in overdose cases.

• blood is passed over an adsorbent substance in order to remove toxic substances in the blood
• molecules or particles of a toxic substance are attracted to the surface of a solid absorbant material and adhere to it.
• hemoperfusion may be refered to as an extracorporeal treatment due to the fact that the blood is processed outside the patient’s body.

Sorbant or toxic chemical attractant materials:

• resins
• activated charcoal
• activated carbon

Application:

removal of nephrotoxic drugs (kidney damaging drugs) or poisons from the blood in emergency situations (such as drug overdoses)

removal of waste products from the blood in patients with impaired kidney function or kidney disease

used to provide supportive treatment before and after transplantation for patients in liver failure, functions in blood metabolic waste product removal.

Process:

• A hemoperfusion system can be used with or without a hemodialysis machine.
• the patient is made comfortable
• two catheters are placed in the arm, one in an artery and one in a nearby vein.
• the catheter in the artery is connected to tubing leading into the hemoperfusion system
• the catheter in the vein is connected to tubing leading from the system through a pressure monitor.
• The patient is given heparin  (to thin the blood and prevent clotting) at the beginning of the procedure and at 15–20-minute intervals throughout the hemoperfusion.
• The patient’s blood pressure is also taken regularly.
• A typical hemoperfusion treatment takes about three hours.
• Hemoperfusion functions to pump the blood drawn through the arterial catheter into a column or cartridge containing the sorbent material (to attract and bind the toxic substance).
•  As the blood passes over the carbon or resin particles in the column, the toxic molecules or particles are drawn to the surfaces of the sorbent particles and trapped within the column.
• The blood flows out the other end of the column and is returned to the patient through the tubing attached to the venous catheter.
• Hemoperfusion is able to clear toxins from a larger volume of blood than hemodialysis or other filtration methods; it can process over 300 mL of blood per minute.

Hayano, Syunichi, Kawasaki, Chiyo, Nishi, Reiko, Otagiri, Masaki, and Uekihara, Souichi. 2000. Charcoal hemoperfusion in the treatment of phenytoin overdose. American journal of kidney diseases. 35 (2): 323-326.

Hemoperfusion. retrived April 24, 2009 from http://www.surgeryencyclopedia.com/Fi-La/Hemoperfusion.html

Ketogenic diet: role in seizure control

A ketogenic diet is one that causes the body to breakdown or use ketones to produce energy to supply the body’s metabolic demands.

A ketogenic diet is one that contains a high in lipid content (fat), protein, and low in carbohydrates. It is primarily used in the treatment and mangement of childhood seizures that are very difficult to control via other means.

The ketogenic diet forces the human body to burn lipids derive energy. Ketogenesis is a much more energy intensvie process than  obtaining energy in the from of glucose through the breakdown of carbohydrates in our diet.

Typically the body obtains the majority of its energy through carbohydrate digestion. Carbohydrates are brokendown to disaccharides then into monosaccharides (glucose).

 

Carbohydrate Digestion

 

Carbohydrate

• Salivary amylase: produced in saliva glands and acts in the mouth and the stomach until denatured by stomach acid

• Pancreatic amylase:produced by the pancreas and acts in the small intestine

 

Disaccharides (maltose, lactose, sucrose)

• Maltase:all 3 emzymes are produced on the intestinal brush border of the duodenum and

• Lactase jejunum.

• Sucrase

 

Monosaccharides

• absorption accross the intestinal epitheliumof the jejumun and the ileum by facitilted diffusion or co-transport proteins

• enter capillaries of the jejunum and ileum by facilitated diffusion

• monosaccharides are then transproted to the liver via the hepatic portal vein for blood sugar regulation

A ketogenic diet is predominantly comprised of  lipids such as oils, butter, and whipping cream. When the body’s only option to produce energy is through the breakdown of lipids, the resultant digestion process is known as ketosis. When fats are burned incompletely, ketones are produced. Fats are burned incompletely in the absence of sufficient glucose.

 

Lipid digestion

Lipids

• Bile salts:produced by the liver, stored and released by the gall bladder into the duodenum via the cystic duct, the common hepatic duct which becomes the common bile duct and the spincter of Oddi to emulsify fats.

• H2O and HCO3 present in bile neutralize acidic chyme

• lecithin present in bile salts forms micelles around lipids allowing them to be transported

 

Small lipid droplets (triglycerides)

• Lingual lipase: from under the tongue, acts in the mouth

• Pancreatic Lipase:produced and secreted by the pancrease into the duodenum.

 

Monoglycerides and Fatty Acids

• surrounded by lecithin, create micelles that allow lipid to be transported

• enter into duodenal and jejunum epithelium

• reformed into tryglycerides

• wrapped in proteins for transport called chylomicrons

• lipids enter lacteals by exocytosis

• enter lymph vessels

• transported to heartas lymph empties into the left internal jugular vein and the right subclavien vein

• enter blood circulation

Lipid metabolism (energy production)

• Lipids (triglycerides) are converted into glycerol and fatty acids through a process called lipolysis.
• glycerol and fatty acids then enter into the kreb’s cycle to produce energy in the form of ATP
• this energy is used by all cells in the body
• fatty acids are converted into ketones by the liver, then enter the kreb’s cycle to make ATP
• in ketosis, ketones are the predominant energy source for the body

 

Typically, our bodies derive the majority of its energy through carbohydrate metabolism and glucose is the predominant energy source.

The ketogenic diet

The “classic” ketogenic diet contains a 4:1 ratio by weight of fat to combined protein and carbohydrate.

This is achieved by eliminating foods high in carbohydrates (starchy fruits and vegetables, bread, pasta, grains and sugar) while increasing the consumption of foods high in fat (cream and butter).

Ketogenic diet and seizure control

• a ketogenic diet has been used for years to manage seizures where partial or complete symptom relief is not able to be acheived through antiepileptic medications.
• The biochemical basis of the dietary effect is unclear.
• The diet alters metabolism of amino acids in the brain
• one of these amino acids is glutamic acid, a major excitatory neurotransmitter

Research shows that:

1) the diet results in a decrease in the rate of glutamate transamination to aspartate that occurs due to reduced availability of oxaloacetate, the ketoacid precursor to aspartate

2) the ketosis process also increases conversion of glutamate to GABA, gamma aminobutyric acid: an amino acid that is found in the central nervous system; acts as an inhibitory neurotransmitter

3) increased uptake of neutral amino acids into the brain.

These three findings may suggest the method of ketosis on effectively controlling previously difficult-to-control seizures in the brain.

 Martini, Fredric, H. 2006. Fundamentals of anatomy and physiology. 7th ed. Pearson Education Inc. USA.

Daikhin, Yevgeny, Lazarow, Adam, Nissim, Ilana, Nissim, Itzhak, and Yudkoff Marc. 2001.  Ketogenic diet, amino acid metabolism, and seizure control. Journal of Neuroscience Research. 66 (5) : 931 - 940.

Myelodysplastic Syndromes

Haematologic syndromes result in the ineffective production of myeloid blood cells.

Myeloid stem cells are those that give rise to:

1. leukocytes
2. red blood cells (function in gas exchange, oxygen transport)
3. thrombocyte or platelets (essential for blood clotting )

 

Leukocytes that arise from myeloid stem cells (cells of the immune system) :

1. macrophages (phagocytize, engulf pathogens)
2. basophils (stimulate the inflammatory response)
3. neutrophils (phagocytize, engulf pathogens)
4. eosinophils (stimulate the body’s allergy response and target parasites)

The above myeloid cells function as part of the body’s immune system in defense against foreign pathogens, function in blood coagulation and oxygen transport.

Myelodysplastice syndromes may result in

• anemia
• predispose an individual to acute myeloid leukemia
• impair the body’s immune response increasing an individual’s risk of succumbing to infection
• predispose an individual to haemorhage risk as platlet action in the role of blood clotting may be compromised

Myelodysplastic syndromes are bone marrow stem cell disorders resulting in disorderly and ineffective haematopoiesis (blood cell formation).

Myelodysplastic syndromes are progressive and chronic.

Diagnosis:

• complete blood cell count - determines numbers of leukocytes (white blood cells), erythrocytes (red blood cells) and platlets
• bone marrow biopsy to examine the source of haematopoiesis (blood cell production)

Treatment:

• control symptoms, improve quality of life, improve overall survival, and decrease progression to acute myeloid leukemia
• blood transfusions to improve red and white blood cell counts and platelet counts
• hormone and drug therapies to increase blood cell production
• bone marrow transplants

 Buresh, Andrew, Fuchs, Heaton, Ruth, Deborah, Knight, Robert, Kurtin, Sandy, List, Alan, Mahadevan, Daruka, Rimsza, Lisa, Roe, Denise J, and Zeldis, Jerome B. 2005. Efficacy of Lenalidomide in Myelodysplastic Syndromes. New England Journal of Medicine. 352:549-557.

Cholangiocarcinoma

Cholangiocarcinoma is cancer of the bile ducts. Bile is produced by the liver, stored in the gall bladder, then released into the small intestine as needed in lipid (fat) digestion.

 

Flow of bile from site of synthesis to site of secretion

• Hepatocytes (cells of the liver)

• Bile canaliculi

• Bile ductules

• Bile ducts

• Right and Left hepatic portal ducts

then either:

1) bile is released directly after synthesis by the liver into the small intestine

•  

  • common hepatic duct

  • common bile duct

  • duodenum

or

2) bile is transported to the gall bladder for storage, then released when needed into the small intestine

 

• cystic duct

• gall bladder

• cystic duct

• common duct

• duodenum

 Cholangiocarcinoma is a relatively rare form of cancer with an incidence of only 1-2 cases/100 000 in North America.

Symptoms:

• abdominal pain
• jaundice
• weight loss
• generalized iching
• fever
• changes in stool and urine colour

Diagnosis:

• low liver function test results
• blood test
• endoscopy

Treatment:

• complete hepatic resection
• chemotherapy and radiation therapy
• palliative measures: pain and symptoms management

Blumgart, Leslie, H, Bodniewicz, Jessica, Burke, Edmund, C, DeMatteo, Ronald, P, Jarnagin, William, R, Fong, Yuman, Gonen, Mithat, Klimstra, David, Youssef, Miranda. 2001. Staging, Resectability, and Outcome in 225 Patients With Hilar Cholangiocarcinoma. Annals of Surgery. 234 (4): 507-519.

 Martini, Fredric, H. 2006. Fundamentals of anatomy and physiology. 7th ed. Pearson Education Inc. USA.

Hypersensitivity pneumonitis (extrinsic allergic alveolitis)

Hypersensitivity pneumonitis is a condition where the lungs become infalmmed due to exposure to an environmental allergen to which the individual has ben previously sensitized.

Symptoms:

• dyspnea
• cough

The disease may be of chronic nature with symptoms lasting more than a year (Lynch et al, 1995). The disease may be chronic and progressive. In some cases the disease may progress to end stage lung disease where the lung can no longer supply tissues with sufficient oxygen to meet the body’s metabolic needs (Ando et al, 2003).

Diagnosis:

confirmed through the following

• demonstration of interstitial markings on chest radiographs
• serum precipitating antibodies against offending antigens
• a lymphocytic alveolitis on bronchoalveolar lavage (BAL), and/or a granulomatous reaction on lung biopsies.

Type	Specific antigen	Exposure
Bird-Breeder’s Lung Also called Bird fancier’s lung, Pigeon-Breeder’s Lung, and Poultry-Worker’s Lung.	Avian proteins	Feathers and bird droppings [2]
Farmer’s Lung	The molds Thermophilic actinomycetes[2] Aspergillus species Saccharopolyspora rectivirgula, and Micropolyspora faeni.	Generally from moldy hay[2] but may be found elsewhere.
Bagassosis	Thermophilic actinomycetes[2]	Moldy bagasse (pressed sugarcane).
Malt Worker’s Lung	Aspergillus clavatus[2]	Moldy barley.
Maple bark disease	Cryptostroma corticale[2]	Moldy maple bark
Miller’s lung	Sitophilus granarius (wheat weevil)[2]	Dust-contaminated grain[2]
Humidifier Lung	The bacterias T. candidus Bacillus subtilis B. cereus, and Klebsiella oxytoca; Thermophilic actinomycetes[2] the fungus Aureobasidium pullulans; [2] and the amoebae Naegleria gruberi, Acanthamoeba polyhaga, and Acanthamoeba castellani.	Mist generated by a machine from standing water.
Mushroom Worker’s Lung	Thermophilic actinomycetes	Exposure is from mushroom compost.
Compost Lung	Aspergillus	compost.
Peat Moss Worker’s Lung	Caused by Monocillium sp. and Penicillium citreonigrum	Peat moss.
Suberosis	Penicillum frequentans	Moldy cork dust.
Japanese Summer-Type HP	Trichosporon cutaneum	Damp wood and mats.
Cheese-Washer’s Lung	Pencillum casei[2] or P.roqueforti	Cheese casings.
Metalworking Fluids HP	Nontuberculous Mycobacteria.	Mist from metalworking fluids.
Hot Tub Lung	Mycobacterium avium complex	Mist from hot tubs.
Mollusc Shell HP	Aquatic animal proteins	Mollusc shell dust.
Isocyanate HP	TDI, HDI, and MDI	Paints, resins, and polyurethane foams.
TMA HP chemical worker’s lung[2]	Trimellitic anhydride[2]	Plastics, resins, and paints.
Berylliosis	Beryllium	Electronics industry.
Wine-grower’s lung	Botrytis cinerea mold	Moldy grapes
Lifeguard Lung	Aerosolized Endotoxin	Prolonged exposure to poor ventilation in an indoor aquatic facility

Treatment

 

Treating hypersensitivity pneumonitis (HP) involves both identifying and removing the antigen that’s causing the condition, and taking anti-inflammatory medication.

Removing the Antigen: If the inhaled antigen can be recognized and removed, the lung inflammation in acute HP is often reversible.

 

Lynch, DA, Newell, JD, Logan, PM, King Jr, TE and Muller NL. 1995. Can CT distinguish hypersensitivity pneumonitis from idiopathic pulmonary fibrosis? American Journal of Roentgenology. 165: 807-811. 

Ando, Masayuki, Colby, Thomas V , Cormier, Yvon, Costabel, Ulrich, Dalphin, Jean-Charles, Erkinjuntti-Pekkanen, Riitta, Lacasse, Yves, Morell, Ferran, Müller, Selman, Moises , Schuyler, Mark. 2003. Clinical Diagnosis of Hypersensitivity Pneumonitis. American Journal of Respiratory and Critical Care Medicine. 168: 952-958.
   

Lyme disease

 

Lyme disease

 

Lyme disease in North America is predominately caused by the bacteria Borrelia burgdorferi. Borrelia afzelii and Borrelia garini cause the majority of Lyme disease cases in Europe. The bacterium causing Lyme disease is transmitted to humans through infected tick bites. However, Borrelia strains can be carried by mice, squirrels and other types of small animals.

 

Types of ticks that transmit Borrelia burgdorferi:

 

• Black legged tick

• Deer Tick

 

 

Symptoms:

 

• fatigue

• stabbing and shooting pain

• blurred vision

• memory loss and cognitive problems

• headache

• swollen joints

• stiff neck

• may not always present with characteristic bull’s eye rash

Acute or chronic?

• caught early, one course of antibiotic treatment may be sufficient to treat the infection

• late stages are very difficult or impossible to completely treat and eradicate

• may result in long term (even life long) chronic infection

• Chronic Lyme disease may result in patients who have completed a course of antibiotic treatment yet continue to have symptoms such as severe fatigue, sleep disturbance, and cognitive difficulties.

Chronic Lyme disease is responsible for a range of medical symptoms beyond the objectively recognized manifestations of late Lyme disease. Long-term antibiotic treatment is warranted in these persistent symptomatic cases.

Due to environmental changes such as global warming the range of tick habitat continues to spread throughout North America. This is leading to persons being infected in areas where Lyme disease was previously unheard of.

ticks may now carry and infect an individual with multiple pathogens. This is called co-infection. Co-infection may overwhelm an individual’s immune system. This may result in a longer and more challenging treatment term.

Fetal Infection in Utero:

It has been discovered that Barrellia bacteria are capable to crossing the placenta and infecting the developing fetus in utero.

This can lead to miscarriages.

Additionally, in utero inections may cause severe health complicatrions at or shortly after birth.

A child infected with Barrelia sp. in utero may suffer from permanent developmental disabilities and mental impairment.

Treatment:

antibiotic are used to target the Borrelia sp and cure Lyme disease

•  doxycycline
• amoxicillin
• ceftriaxone

Most cases of Lyme disease can be cured with a 2-4 weeks of treatment

Persons with certain neurological or cardiac forms of illness may require intravenous treatment with:

•  penicillin 
• ceftriaxone

 Patients diagnosed in the later stages of the disease can have persistent or recurrent symptoms requiring a longer course of antibiotic treatment.

In some cases with persisent symptoms patients may require long-term antibiotic treatment.

Canadian Lyme Disease Foundation. 2009. retrieved April 18, 2009 from http://www.canlyme.com/

Public Health Agency of Canada. 2009. Lyme Disease. retrived April 18, 2009 from http://www.phac-aspc.gc.ca/id-mi/lyme-fs-eng.php#6