Normal Pressure Hydrocephalus (NPH)

01/05/2009

Normal pressure hydrocephalus is an increase in pressure within the ventricles of the brain. In NPH, raised CSF pressure causes lower cerebrospinal fluid (CSF) production. Additionally, the aging process also contribiutes to lower CSF production.

normal-pressure-hydrocephalus1

Symptoms:

Urinary incontinence (45-90%)

            – may initially only complain of urgency / frequency

            – rarely may also have fecal incontinence

Mental impairment (up to 80%)

– subcortical-like dementia

– slowing of verbal and motor responses (bradyphrenia)

– apathetic, forgetfulness, decreased attention

– preservation of cortical functions e.g. language

– frontal release signs may be present (snout, glabellar tap, palmomental)

Gait disturbance (up to 90%)

– “apraxic” or “magnetic” gait, inability to life legs as if they are stuck to the floor

– often confused with Parkinsonism(eg vascular) since patient’s may display balance difficulty, shortened stride length, difficulty turning and paratonic rigidity but NPH more broad based, outward rotated feet and diminished height of steps

Causes:

Primary / Idiopathic, disease arising from unknown cause (1/3)

Secondary causes:

           1) Trauma

         2) Infection e.g meningitis

3) Subarachnoid Haemorrhage (SAH)

Bleeding within the head into the space between two membranes that surround the brain.

 The bleeding is beneath the arachnoid membrane and just above the pia mater

       4)     Mucopolysaccharidosis of the meninges

metabolic disorders caused by the absence or malfunctioning of lysosomal enzymes needed to break down molecules called glycosaminoglycans – long chains of sugar carbohydrates in each of our cells that help build bone, cartilage, tendons, corneas, skin and connective tissue.

       5)     Achondroplasia (skeltal disorder causing dwarfism)

Treatment and symptom management:

  • Ventriculoperitoneal shunting

Mayo M, McGuire D, Saul T, Silverberg GD, Rubenstein E. (2003). Alzheimer’s disease, normal-pressure hydrocephalus, and senescent changes in CSF circulatory physiology: a hypothesis. Lancet Neurology. 2(8):506-11.

Neurological Medicine Pocketbook. 2004 Retrived May 1, 2009 from http://www.uwo.ca/cns/resident/pocketbook/disorders/cognitive/nph.htm

Vanneste, J. A. L. (2000) Diagnosis and management of normal-pressure hydrocephalus. Journal of Neurology. 247 (1) 5-14.


Progeria (Hutchinson-Gilford syndrome)

29/04/2009

progeriaProgeria 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.progeria-cells

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.


Zoonosis

27/04/2009

zoonoticdiseasetransmission 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

zoonosis

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

25/04/2009

 

pigs3

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.influenza-virus

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/


Ketogenic diet: role in seizure control

23/04/2009

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

ketosis

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.ketogenic-diet

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

22/04/2009

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

Myeloid stem cells are those that give rise to:bone_marrow-blood-cells

  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).

blood-stem-cells1

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.

Hypersensitivity pneumonitis (extrinsic allergic alveolitis)

20/04/2009

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.

hypersensitivity-pneumonitis-flow-chart

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:hypersensitivity-pneumonitis-eosinophil

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

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

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

hypersensitivity-pneumonitis-radiograph

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.