Biliary Colic (gallbladder pain)

Biliary colic results in pain arising from gallstones impinging on the walls of the biliary tract or the gallbladder sphincter. Biliary colic is painful and affects breathing. There is severe vomiting on an empty stomach as patient cannot consume any food. Vomitus is clear white or clear yellowish. There is no change in bowel habit (BO) or passing urine (PU). There is no associated fever but there is profused sweating and patient feels cold. A patient with biliary colic ends up in the A&E in the wee hours of the morning.

A&E Admisison
The patient is brought to A&E in a wheelchair early in the morning at 7 am. Breathing is laboured. Patient is in great pain, very tired and eyes closed.

A&E Investigations
BP is checked and is high 190/113.
Blood is taken from a butterfly IV line and sent to A&E Lab for analysis
BUSE, cardiac enzymes - normal.
Serum amylase was not done
Since patient is in severe pain, morphine IV is administered in 4 doses.
Once patient is not affected by excrutiating pain, questions can be asked.
ECG was done since heart problem was suspected
ECG was normal

A&E Questions Asked
Source of pain and from where it arise: lumbar, upper right epigastric region
Spread of pain: from right back shoulder, to right side, to under right breast
Intense pain won't go away before morphine administration
Pain is reduced after morphine injection and becomes bearable

Medical History
Two small gallbladder stones were detected 3 years ago, not followed up
This is the first eipsode in 3 years after first diagnosis
Patient was advised to go for gallbladder surgery but patient was unwilling (willing to wait)
Now the intense pain makes surgery the only option

Ultrasound Investigation
One gallbladder stone (2cmx1cm) was detected, not 2 stones
This time the stone is big and needs to be removed
Appointment for ultrasound 10 July 2013
Gallbladder surgery scheduled for after 20 August 2013; next available slot is 28 September 2013

Prescriptions
For the time being, while waiting for ultrasound and gallbladder surgery, these drugs were prescribed:
1. Amlodipine Besylate 10mg
2. Tramadol HCl 50mg
3. Metoclopramide 10mg
4. Celecoxib 200mg

Patient is discharged from A&E Day Ward at 3 pm.

External links:
http://www.healthline.com/health/gallstones#Overview1

Gallbladder pain - How to know if what you are feeling is gallbladder pain
https://youtu.be/ez14kQOx7is

Chromosome Aberrations Test

1. Mutagens and structural chromosome aberrations

Structural chromosome aberrations may be induced via DNA breaks by various types of mutagens. Such DNA breaks may either rejoin such that the chromosome is restored to its original state, rejoin incorrectly or not rejoin at all. These last two cases may be observable on microscopic preparations of metaphase cells. However, many of these gross changes probably will not allow cell survival after division, but they serve as indicators for the induction of smaller, not readily observable changes, which do allow cell survival but may have deleterious consequences for the organism.

2. Chromosome aberration test

The chromosome aberration test is most often performed on human peripheral blood lymphocytes. As peripheral lymphocytes are in the resting G0 stage of the cell cycle, they have to be stimulated to divide by an aspecific antigen, like phytohaemagglutinin. After 46.5 hours just before fixation (at 48 hours) a spindle inhibitor like colcemid is added to block the cells in the (pro)metaphase of the first mitosis.

3. Induced chromosomal aberrations

Induced chromosomal aberrations can be divided into two main classes: chromosome-type aberrations, involving both chromatids of a chromosome, and chromatid-type aberrations involving only one of the two chromatids. Ionizing radiation induces chromosome-type aberrations (symmetric aberrations), like dicentrics, inversions, ring chromosomes, in the G0 or G1 stage of the cell cycle (i.e. prior to replication), while chromatid type aberrations (asymmetric aberrations), like breaks and gaps, are produced during the S or G2 stage (i.e. during or after replication). Mostchemical mutagens are S-dependent clastogens and therefore produce chromatid-type aberrations.

4. Types of aberrations

Several types of aberrations can be distinguished and grouped into 2 types: structural, numerical.

(i) Structural aberrations:

• gaps
• breaks
• dicentric chromosomes
• ring chromosomes

(ii) Numerical aberrations: (not adequate because of technical artefacts with spreading)

• polyploidy (4n)
• hypodiploidy (< 46chr)
• hyperdiploidy (> 46chr)

5. Characteristics of chromosome aberration (CA) test:

• Biomarker of effect: highly relevant for cancer risk assessment.
• End-point: chromosome (and genome) mutations
• Discrimination between chromatid type aberrations, chromosome type aberrations

6. Advantages

• Cell/ cell approach
• Accurate identification of all the different chromosome mutation types
• Possible co-detection of mitotic indices
• No full automatic but interactive scoring possible

7. Disadvantages

• Requires in vitro cell cultivation
• Labor intensive
• Requires highly qualified skills and experience

8. Confounding factors

• smoking
• age

Source:

http://www.crios.be/genotoxicitytests/chromosome_aberrations.htm

Genotoxicity and Comet Assay

1. Background on DNA damage

DNA damage, due to environmental factors and normal metabolic processes inside the cell, occurs at a rate of 1,000 to 1,000,000 molecular lesions per cell per day. While this counts for only a small part of the human genome's approximately 6 billion bases (3 billion base pairs), unrepaired lesions to critical genes can impede a cell's ability to carry out its function.

2. DNA damage and cancer

When DNA is damaged and DNA repair is not sufficient, and the cell cannot function properly, it increases the likelihood of cancer.

3. Technique for measuring DNA damage

The comet assay is a well-published method for measuring cellular DNA damage.

The comet assay is used universally for the detection of DNA damage.
Comet assay kits and slides can detect DNA / RNA damage and modification.
It is a useful screening tool for various types of DNA damage.

The alkaline SCG assay can be effectively used to evaluate the in vivo genotoxicity of chemicals in multiple organs, providing for a good assessment of potential carcinogenicity.

4. Comet assay

The comet assay is also known as single-cell gel electrophoresis (SCGE) assay. This simple assay has many scientific applications. It is a common technique for measurement of DNA damage in individual cells. Under an electrophoretic field, damaged cellular DNA (containing fragments and strand breaks) is separated from intact DNA, yielding a classic “comet tail” shape under the fluorescent microscope. Extent of DNA damage is usually visually estimated by comet tail measurement; however, image analysis software is also available for measuring various parameters.

Different versions of Comet Assay:

http://www.cometassay.com/index_files/Page290.htm

1. Alkaline Comet Assay
2. Neutral Comet Assay
3. Comet assay at pH 12.1
4. Comet assay with DNA repair enzymes
5. Acellular Comet Assay
6. Comet-FISH Assay
7. Bromodeoxyuridine Labeling to Detect Replicating DNA
8. Detection of incomplete DNA excision repair sites
9. Halo assay or non-electrophoretic assay

5. Performance of the comet assay
The comet assay is sufficiently sensitivite for detecting genotoxicity
http://www.hindawi.com/journals/jna/2010/541050/

6. Commercial assay kits

The DNA damage is quantified by measuring the displacement between the genetic material of the nucleus ('comet head') and the resulting 'tail'. Tail Moment and Tail DNA% are the two most commonly parameters to analyze comet assay results. At least 50 -100 cells should be analyzed per sample. The Tail Moment has been suggested to be an appropriate index of induced DNA damage in considering both the migration of the genetic material as well as the relative amount of DNA in the tail.

Tail DNA% = 100 x Tail DNA Intensity/Cell DNA Intensity
Tail Moment can be measured using one of the following methods:
(a) Olive Tail Moment = Tail DNA% x Tail Moment Length*
(b) Extent Tail Moment = Tail DNA% x Length of Tail (see diagram)

*Tail Moment Length is measured from the center of the head to the center of the tail (see diagram)

7. Comet analysis software programs

A number of comet analysis software programs are commercially available, such as:

1. LACAAS from Loats Associates, Inc. http://www.loats.com/comet.html and 

2. Comet Assay IV from Perceptive Instruments http://www.scorecomets.com/

3. WOLFRAM Comet Assay Analysis http://library.wolfram.com/examples/cometassay/

8. Comet Assay IV scoring system

http://www.scorecomets.com/comet-scoring/comet-assay-iv

http://www.scorecomets.com/comet-scoring/comet-assay-iv/scoring

http://www.scorecomets.com/images/pdf/cometassayiv.pdf

Comet Assay IV is the world's fastest, most consistent comet assay scoring system. Scoring with Comet Assay IV is a uniquely effortless process. Just click on each comet to get your results.

Comet Assay IV^TM is the latest in a highly successful series of comet scoring systems from Perceptive Instruments. Comet Assay IV is the professional choice for those seeking accuracy, reproducibility and GLP compliance.

Comet Assay IV has the ability to score comets from a live video. This makes Comet Assay IV the fastest, easiest and most accurate way to score comets to date.

Comet Assay IV is supplied with a FireWire video camera delivering 3x the resolution of previous models. This makes it possible to use lower power microscope objectives, offering a larger field of view and greater depth of field. This combination greatly improves scoring speed, with more comets per field and less time spent at the controls of the microscope.

Getting started with Comet Assay IV is as simple as installing the software and connecting the camera.This can be done in a few minutes either by yourself or your IT department. Once running, Comet Assay IV displays a live video image onscreen that mirrors what you see by looking down the microscope's eyepiece. Any refocusing or stage movements performed at the microscope level are shown live on screen without any lag or delay.

9. Cell Biolabs comet assay kit

http://www.cellbiolabs.com/sites/default/files/STA-354-comet-assay-control-cells.pdf

The OxiSelect™ Comet Assay Kits provide a fast, convenient way to screen for general DNA damage, regardless of the source or nature of the damage.

The OxiSelect™ Comet Assay Control Cells set contains both positive and negative control cells for detection by fluorescence microscopy.

The OxiSelect™ Comet Assay Control Cells are provided as a set; the set containing vials of healthy, untreated cells and DNA damaged, Etoposide-treated cells. These cells are intended for use as controls in the Cell Biolabs’ OxiSelect™ Comet Assay under alkaline electrophoresis conditions. 

10. Cell Biolabs comet assay procedure

Cell Biolabs’ OxiSelect™ Comet Assay Control Cells are designed for use in a single cell gel electrophoresis assay (SCGE) for simple evaluation of cellular DNA damage (under alkaline conditions). 

1. First, individual cells are mixed with molten agarose before application to the OxiSelect™ Comet Slide. 
2. These embedded cells are then treated with a lysis buffer and alkaline solution, which relaxes and denatures the DNA. 
3. Finally, the samples are electrophoresed in a horizontal chamber to separate intact DNA from damaged fragments. 
4. Following alkaline electrophoresis, the samples are dried, stained with a DNA dye, and visualized by epifluorescence microscopy. 
5. Under these conditions, the damaged DNA (containing cleavage and strand breaks) will migrate further than intact DNA and produce a “comet tail” shape. 
6. For a complete protocol, refer to Cell Biolabs’ OxiSelect™ Comet Assay Kit insert (STA-350). 

11. Comet assay special interest group

http://www.cometassay.com/index_files/Page338.htm

12. References

1. Ostling, O., and Johanson, K. J. (1984). Micro gel electrophoretic study of radiation induced DNA damages in individual mammalian cells. Biochem. Biophys. Res. Commun. 123, 291–298.
2. Singh, N. P., McCoy, M. T., Tice, R. R., and Schneider, E. L. (1988). A simple technique for quantification of low levels of DNA damage in individual cells. Exp. Cell. Res. 175, 184–191.
3. Olive, P. L., Banath, J. P., and Durand, R. E. (1990a). Heterogeneity in radiation induced DNA damage and repair in tumor and normal cells using the "Comet" assay. Radiat. Res. 122, 86–94.
4. De Boeck, M., Touil, N., De Visscher, G., Vande, P. A., and Kirsch-Volders, M. (2000). Validation and implementation of an internal standard in Comet assay. Mutat. Res. 469, 181–197.
5. Yu F Sasakia, Keiko Fujikawaa, Kumiko Ishidaa, et al. The alkaline single cell gel electrophoresis assay with mouse multiple organs: results with 30 aromatic amines evaluated by the IARC and U.S. NTP. http://www.sciencedirect.com/science/article/pii/S1383571899000066

Study Questions

What is the comet assay?

How is the comet assay performed?
What is the comet assay good for?
Is the comet assay sensitive for detecting genotoxicity?

Acupuncture: Experts claim it doesn't work

An NHS hospital offering acupuncture has been slammed by watchdogs for making bogus claims about how the technique can cure a remarkable range of ills.

The Royal London Hospital for Integrated Medicine (RLHIM), which offers alternative treatments from hypnosis to homeopathy, has been told to stop misleading patients.

The hospital, which is part of the NHS, issued two leaflets boasting about the efficacy of the ancient Chinese therapy, which involves inserting pins into pressure points on the body.

It claimed that acupuncture could treat a long list of ailments, ranging from gynaecological and urinary disorders to fertility issues, stress, depression, back pain, asthma and high blood pressure.

However, the Advertising Standards Authority (ASA) consulted medical experts and found there was no robust evidence to back up the vast majority of the cures claimed.

It has ordered the hospital to withdraw the leaflets and to stop making claims for acupuncture that cannot be substantiated by good and independent evidence.

The ruling raises questions as to why millions of pounds taxpayers money is being used to fund alternative health treatments where there is little or no evidence that they work.

The first leaflet issued by the hospital stated: ‘Acupuncture is a part of Traditional Chinese Medicine, a system of healing which has been practised in China and other Eastern countries for thousands of years.’

http://www.dailymail.co.uk/news/article-2339968/Dont-claim-acupuncture-works-NHS-hospital-told-Institution-criticised-leaflets-bogus-claims-treatment.html#ixzz2VzJkEcd2

German Miracle Pill: Pervitin

The 22-year-old, who wrote numerous letters home begging for more Pervitin, was not just any soldier -- he was Heinrich Böll, who would go on to become one of Germany's leading postwar writers and win a Nobel Prize for literature in 1972. And the drug he asked for is now illegal, notoriously so. We now know it as crystal meth.

German Miracle Pill

It was in Germany, though, that the drug first became popular. When the then-Berlin-based drug maker Temmler Werke launched its methamphetamine compound onto the market in 1938, high-ranking army physiologist Otto Ranke saw in it a true miracle drug that could keep tired pilots alert and an entire army euphoric. It was the ideal war drug. In September 1939, Ranke tested the drug on university students, who were suddenly capable of impressive productivity despite being short on sleep.

From that point on, the Wehrmacht, Germany's World War II army, distributed millions of the tablets to soldiers on the front, who soon dubbed the stimulant "Panzerschokolade" ("tank chocolate"). British newspapers reported that German soldiers were using a "miracle pill." But for many soldiers, the miracle became a nightmare.

As enticing as the drug was, its long-term effects on the human body were just as devastating. Short rest periods weren't enough to make up for long stretches of wakefulness, and the soldiers quickly became addicted to the stimulant. And with addiction came sweating, dizziness, depression and hallucinations. There were soldiers who died of heart failure and others who shot themselves during psychotic phases. More at http://www.spiegel.de/international/germany/crystal-meth-origins-link-back-to-nazi-germany-and-world-war-ii-a-901755.html 

Do not temper with nature

A truck driver is suing a doctor after he was left with an erection that lasted for eight months and a scrotum the size of a volleyball following penile implant surgery.

Read more: http://www.dailymail.co.uk/health/article-2340151/Man-sues-doctor-surgery-leaves-month-erection.html#ixzz2W519PL9N

Nano: Finer than fine

Nano is a new buzz word. Not only that, there is a lovely song entitled Awan Nano. Find it and listen to it on YouTube. Awan Nano song

What is nano? Nano is finer than fine. Nano is 10 to exponent-9. It means a nano particle is 9 times finer than fine.

What is wrong or right about nano particles? Now I will tell you what is good or bad about nano particles. I didn't make up this story. It was our discussion over dinner at Motorola engineer's home, one fine night.

This is the good about nano...

When particles are made superfine, they taste better - fine chocolate powder gives the fine taste of high quality chocolates. The chocolate powder is ground so very fine (we call it superfine in the research lab), that these chocolate particles enter every crevice in the tongue to trigger a fine chocolaty taste of fine chocolates.

Now there is a problem when we use superfine particles in other foods. Imagine we use superfine whitener particles in white flour, in toothpaste, in everything we like to eat. What will happen? What can possibly happen? To give you an idea of the possible grave concern is what IF the superfine nano particles decide to travel and traverse anywhere in the body? Where do you think superfine nano particles end up in the body after we eat superfine nano particles? Any idea?

Imagine if superfine nano particles decide to travel into the brain and stay put in the brain! What can happen next? Of course the superfine particles will accumulate with time ... and if we get unlucky, the superfine nano particles decide they have had enough and want to break loose, what can happen? What will happen if superfine nano particles want to break up and go somewhere else?

Of course the clump of superfine nano particles can easily break up and go separate ways. What if this time they decide to meet at the heart valves? Yes, sure, they can travel there and disturb the valves without us being aware trouble is brewing in the heart.

What if the superfine nano particles want to travel elsewhere in the body? Let's say the renal tubules. Imagine if the superfine nano particles inside us all decide to visit our kidneys and do some damage there, what will happen to us? Of course we can still wee but a concern is they can also cause damage to the renal tubules.

Now the best part is, imagine if the superfine particles decide to visit our eyes and eye lens. What can go wrong? Yes, they will fill the lens and make them hazy or even opaque. They can fill the eyes and we get eyeballs filled with superfine nano particles. What harm can that do to our eyes? Of course they will cause harm to the eyes, and the fine blood vessels won't like it and will definitely burst all over. So we will get blood-shot eyes, and people around us will think we are Dracula in the making or drunk or something. It can be fun if the blood-shot eyes are temporary. But .... what IF the blood-shot eyes are an indication of permanent damage to the fine capillaries in the eyes? Can we become blind from superfine nano particles? I think so it is possible. We can become blind and blinded by packing more and more superfine nano particles inside our bodies. We want to consume anything that contains the buzz word "nano", often thinking that a bombastic buzz word is always right and good and therefore our body needs a new food. We are often wrong and always have regrets of the worst kind. That's being human.

So when do we say Yes to nano and No to nano? I think we must know where nano particles like to go in the body and use them in moderation so we don't accumulate them in our life. We try to minimise consumption of such nano particles so we don't suffer ill-effects or complications of superfine nano particles.

Next we can expect scientists to create super duper fine nano trillo particles so that they taste just like water and we can consume them without worry. Isn't zamzam water also superfine nano water particles? But we use zamzam water for treatment which is putting superfine nano particles to good use. That's some thoughts about nano particles.