:::simple medicine:::

- Genetic testing.

2024-07-12T23:59:00.001+03:00

Genetic testing

Def: Genetic testing identifies changes in chromosomes, genes, or proteins.

Importance: can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder.

More than 1,000 genetic tests are currently in use, and more are being developed.

Knowledge of the test result could lead to emotional and social problems in the child, altering both relationships within a family and expectation for the future in a variety of areas such as education, employment, and relationships.

For many types of genetic analysis, a negative test result must be interpreted with caution in case it is a false negative, i.e a genetic abnormality is actually present but was not detected by the test.

Pathological significance of detected genetic alteration may be unclear due to missense mutation and variable expression.

When preforming genetic testing, it is important to be aware that the diagnosis of a genetic disease will not only have implications for the affected individual but may have ramifications for the other family members, who may be at risk of being affected or of being carriers for the condition.

Several methods can be used for genetic testing:

· Molecular genetic tests (or gene tests): study single genes or short lengths of DNA to identify variations or mutations that lead to a genetic disorder, it depends on base sequences on chromosome.

ü Southern blot analysis

ü The polymerase chain reaction (PCR)

ü DNA sequencing

ü Next generation sequencing (NextGen).

· Cytogenetics: concerned with how the chromosomes relate to cell behavior, particularly to their behavior during mitosis and meiosis include: Karyotyping

· Molecular cytogenetics: involves the combination of molecular biology and cytogenetics

ü Fluorescent in situ hybridization (FISH)

ü Comparative genomic hybridization (CGH).

ü Array comparative genomic hybridization (also microarray-based comparative genomic hybridization, matrix CGH, array CGH, aCGH)

· Biochemical genetic tests study the amount or activity level of proteins; abnormalities in either can indicate changes to the DNA that result in a genetic disorder.

The chromosomes could be sampled from:

˗ Peripheral blood lymphocytes - Bone marrow cells

˗ Skin fibroblast - Solid tissue cells

˗ Amniotic fluid cells

Medical applications (indications of genetic testing, karyotyping, chromosomal culture, analysis) :

1. Multiple congenital anomalies:

Birth defects > one developmental regions of the body

A. Confirmation of a clinical diagnosis

B. Estimate recurrence risk of future sibling

- Cell division.

2024-07-01T23:40:00.002+03:00

Cell division

Two types of cell division: Mitosis and Meiosis

ü Mitosis: occurs in somatic cells and results in cell duplication→ two diploid daughter cells which are genetically identical both to each other and the original parent cell.

ü Meiosis: occurs in the germ cells of the gonads and is also known as ‘reduction division’ because it results in four haploid daughter cells, each containing just one member (homologue) of each chromosome pair, all genetically different.

-Karyotyping.

2024-01-12T23:07:00.004+02:00

Karyotyping

Def: studying chromosomes in a form suitable for analysis during metaphase or Chromosomes are stained and visualized under a microscope.

Steps:

1. As chromosomes are only visible microscopically in dividing cells (metaphase chromosomes)

2. Chromosome analysis involves taking some non-dividing cells (usually peripheral blood lymphocytes)

3. Culturing them to encourage cell division on certain media.

4. Arrest of cellular division in metaphase.

5. Adding hypertonic saline leading to bursting of cells & release of chromosomes.

6. Staining which creates unique banding patterns on the chromosomes and subsequently examines the cells under microscopy for any extra or missing chromosomes, or large scale structural chromosomal abnormalities.

This method will miss any changes smaller than 5–10 megabases (5–10 million bases) in size, so is unsuitable for the detection of most microdeletions or duplications.

Along with array comparative genomic hybridization it is helpful in identifying changes in amount of genetic material – gene copy number variation (CNV) including duplications (increased copy number) and deletions (decreased copy number), so they are useful Investigate broad/complex phenotype.

-Fluorescent in situ hybridization (FISH).

2023-09-13T16:41:00.006+03:00

Fluorescent in situ hybridization (FISH)

Using Fluorescent-labelled DNA probes which are designed that are complementary to the DNA sequences being assessed, to detect and localize the presence or absence of specific DNA sequence on Chromosome.

Steps:

ü Chromosomes are immobilized and denatured on a microscope slide and exposed to a solution containing a fluorescently labelled probe specific to a specific chromosomal region.

ü After hybridization (the formation of a double strand of DNA from complementary single strands), the slide is washed and examined microscopically.

ü Where the probe has hybridized, fluorescent spots are seen over the relevant chromosome.

For example, if a child were suspected of having 22q11 deletion syndrome, FISH using a 22q11-specific probe would show only one pair of fluorescent spots, rather than two.

Types of FISH probes:

ü Centromeric (aneuploidy)

ü Telomeric (subtelomeric rearrangements)

ü Sequence specific (microdeletions)

ü Whole chromosome paint (complex rearrangements)

ü Reverse painting (to identify origin of unidentified chromosomal material)

Useful for microdeletion syndromes.

- From gene to protein!

2023-07-01T22:30:00.006+03:00

Human genes and protein synthesis

Ü Human genes: They are units of DNA sequences that containing information which determine the composition of an RNA molecule and most often translated to a protein.

Ü Every three nucleotides "triplet" represent a single codon, coding for a particular amino acid. Some codons act as a “start” signal, whereas others serve as “stop” signals that terminates translation .

Protein synthesis steps (From gene to protein)

1. DNA replication

ü Replication is semiconservative, i.e. each daughter molecule receives one strand from the parent DNA molecule.

ü Unwinding proteins, DNA-directed RNA polymerase, DNA polymerase and ligase are also required.

ü DNA polymerases synthesize the new strand in a 5' to 3' direction.

ü Discontinuous replication, i.e. one or both DNA strands may be synthesized in pieces known as Okazaki fragments, which are then linked together to yield a continuous DNA chain.

2. Transcription

ü Synthesis of complete RNA molecules from DNA by the enzyme RNA polymerase.

ü Transcription yields three types of RNA: mRNA, tRNA and rRNA.

ü Each nucleotide in the mRNA is complementary to one in the DNA template.

3. Post-transcriptional processing: the initial transcript is edited to remove introns and splice exons together by means of an RNA-protein complex called the spliceosome. Multiple different transcripts may be produced (alternative splicing).

- Gene switch off/ on!

2022-07-02T21:41:00.004+02:00

Gene switch on/off

˗ Each cell expresses (turns on) only a fraction of its genes. The rest of the genes are repressed (turned off).

˗ The process of turning genes on and off is known as gene regulation.

˗ Gene regulation is an important part of normal development.

˗ Genes are turned on and off in different patterns during development to make a brain cell look and act different from a liver cell or a muscle cell, for example.

˗ Gene regulation can occur at any point during gene expression, but most commonly occurs at the level of transcription (when the information in a gene’s DNA is transferred to mRNA).

- Numerical Chromosomal Aberrations.

2021-07-05T17:57:00.012+02:00

Numerical Chromosomal Aberrations:

Aneuoploidy

A chromosome profile with fewer or greater than the normal diploid number where the total is not a multiple of 23.

n If an extra chromosome is present (presence of three copies of the chromosome) : trisomy for that particular chromosome e.g. trisomy 21, trisomy 18, trisomy 13.

Trisomies are the most common numerical chromosomal anomalies found in humans.

Most autosomal aneuploidies are fatal in utero.

Three are survivable to term: Trisomy 13, 18 and 21.

Children with trisomy 21 (Down’s syndrome) are believed to have the most favorable outcome, as chromosome 21 has fewer genes than the other autosomes (it is short and has a low gene density)

Mechanism: Non disjunction (Failure of the two chromosomes of one pair to disjoin).

n If a chromosome is missing: monosomy for that chromosome e.g. Turnersyndrome (monosomy X chromosome).

Mechanism:

ü Non-dysjunction.

ü Anaphase lag; failure of the chromosome to move quickly to be incorporated in the daughter cell, so it will be lost.

- Genetic Counseling.

2019-07-06T12:59:00.008+02:00

Genetic Counseling

Definition: A process of communication and education which deals with estimating the risk of developing and/or transmitting a genetic disorder.

Goals of Genetic Counseling:

The consultand الذى يطلب الاستشارة should be provided with information and support which enables him to understand:

1. The medical diagnosis and its consequences as: prognosis and possible treatment.

2. Mode of inheritance of the disorder and the risk of developing or transmitting it.

3. To make their own decisions about choices or options available for managing a particular disease and those for dealing with genetic testing and reproduction and the following risks.:

ü Recurrence risk in future children

ü Recurrence risk in near relatives

ü Recurrence risk in children of unaffected brothers & sisters

A primary goal of genetic counselling is to provide information to allow for greater autonomy and choice in reproductive decisions and other areas of personal life. Avoiding additional cases of genetic disease in a family may be a consequence of genetic counselling but is not the primary aim.

Indications

1. Maternal age > 35 years

2. Known or suspected hereditary condition in the family

3. Hx of child with birth defect or MR

4. Hx of recurrent abortion

5. Exposure to known or suspected teratogens

6. consanguinity

-Prevention of Genetic Disorders.

2018-07-06T12:51:00.011+02:00

Prevention of Genetic Disorders

Prevention is by 4 ways:

1. Genetic councelling (click here).

2. Carrier detection.

3. Prenatal diagnosis.

4.Neonatal screening.

-Mendel’s principles of inheritance.

2017-07-02T21:54:00.001+02:00

Mendel’s principles of inheritance: U.S.A

Law of dominance
"uniformity"

Some alleles are dominant while others are recessive; an organism with at least one dominant allele will display the effect of the dominant allele.

Law of segregation

During gamete formation, the alleles for each gene segregate from each other so that each gamete carries only one allele (heterozygous) for each gene.

Law of independent assortment

Genes for different traits can segregate independently during the formation of gametes.

In reality, this is not always true, as genes that are close together on the same chromosome tend to be inherited together, i.e. they are 'linked’.

- histamine releasers.

2016-03-14T00:24:00.000+02:00

drugs causing histamine release

(histamine releasers)

"Moon Try To Do Rays"

Morphine

Trimetaphan

Tubocurarine

Deferoxamine

Radiocontrast media.

Dr Ibrahim samaha

Anti pseudomonal antibiotics mnemonics.

2011-12-17T11:07:00.030+02:00

Anti pseudomonal antibiotics mnemonics.

Pig cam

Piperacillin/TazObactam

Imipenem

Gentamicin

Ciprofloxacin/Cefepime/Ceftazidim

Azteronam

Meropnem

Varicocele grading.

2011-12-08T15:50:00.010+02:00

Clinical and ultrasonography grading of varicocele

Varicocele grading is done to provide a standardization in the diagnosis, treatment and follow-up of the disease.

Varicocele staging (grade) is done in two main ways:

1. Grading system made clinically, namely by examination.

2. Grading with scrotal color Doppler ultrasonography.

Clinical Grading of varicocele

Grade	Description
Grade 0	Seen on ultrasound, but not physically detectable (also called “subclinical varicocele”)
Grade I	Palpable (felt on exam) when the patient is performing the valsalva maneuver (“bearing down”)
Grade II	Palpable even without valsalva
Grade III	Varicocele causing visible deformity of the scrotum.

Modified Canadian Cardiovascular Society grading of angina pectoris.

2011-11-06T22:19:00.004+02:00

Modified Canadian Cardiovascular Society

grading of angina pectoris

Canadian Cardiovascular Society grading of angina pectoris contain only 4 grades and Class 0 is not an official part of the CCS functional classification of angina pectoris, however it has been mentioned in several sources, referring to myocardial ischemia without symptoms.

Grade 0	Asymptomatic Angina	Mild myocardial ischemia with no symptoms.
Grade I	Angina only with strenuous exertion	Angina with strenuous or rapid or prolonged exertion at work or recreation (Ordinary physical activity does not cause angina, such as walking and climbing stairs).
Grade II	Angina with moderate exertion	Slight limitation of ordinary activities when they are performed rapidly, after meals, in cold, in wind, under emotional stress, during the first few hours after waking up, but also walking uphill, climbing more than one flight of ordinary stairs at a normal pace and in normal conditions.
Grade III	Angina with mild exertion	Having difficulties walking one or two blocks or climbing one flight of stairs at normal pace and conditions.
Grade IV	Angina at rest	No exertion needed to trigger angina.

Dr Ibrahim

Return to list of medical grades (click here)

- Value of Tracheal tube in general anaethesia.

2011-10-07T02:20:00.000+02:00

Value of Endotracheal tube During general anaethesia (1)

Endotracheal intubation may be considered in every patient receiving general anesthesia for the following purposes:..

- Criteria of hypersplenism.

2011-10-05T01:39:00.000+02:00

Criteria of hypersplenism.

Splenomegally.
Cytopenias (mono or pan).
Hypercellular bone marrow.
Scanning with Cr51 labelled with RBCs>> reversed liver to spleen ratio.
Splenectomy will improve the condition.

(A huge spleen after splenectomy for female patient with hypersplenism)

Dr Ibrahim samaha

- Heel foreign body X-ray.

2011-10-01T01:18:00.000+02:00

Heel foreign body X-ray.

A child presented to Mansoura Emergency Hospital by a needle in heel which not appear on the skin,An X-ray was made and shown this..

Dr Ibrahim samaha

- Arterial Doppler Examination.

2011-09-27T01:10:00.000+02:00

Arterial Doppler Examination.

An Arterial Doppler evaluates the arterial blood flow of the body. It is used many times to evaluate the arteries of the legs.

It may be ordered when there is suspicion on exam or with symptoms suggestive of blockage of the arteries.

There is no radiation for this test as it uses sound waves and pressure cuffs.

This video shows how to interpret vascular arterial doppler signal wave-forms in a simple and informative fashion.

This is educational especially in teaching how to better utilise a simple hand-held Doppler.

- Acupuncture.

2011-09-21T04:11:00.005+02:00

*Acupuncture is an alternative medicine methodology originating in ancient China that treats patients by manipulating thin, solid needles which have been inserted into acupuncture points in the skin.

*Theory

The general theory of acupuncture is based on the premise that there are patterns of energy flow (Qi) through the body that are essential for health. Disruptions of this flow are believed to be responsible for disease. Acupuncture may correct imbalances of flow at identifiable points close to the skin. (1)

- Sher's grading of abruptio placentae.

2011-09-10T19:01:00.003+02:00

Sher's grading of abruptio placentae.
(according to severity)

Grade I (Retrospective) Not recognized clinically before delivery: small retroplacental Haematoma discovered on maternal surface of placenta after delivery, No APH.
Grade II mild vaginal bleeding,uterine tenderness and tetany, No fetal distress, no maternal shock.
Grade III Severe vaginal bleeding, uterine tenderness and tetany, fetal distress then death, maternal shock, according to DIC:

IIIa:Without DIC
IIIb:With DIC

Dr Ibrahim
Return to list of medical grades (click here)

- Eye signs of thyrotoxicosis.

2011-08-23T11:50:00.001+02:00

Eye signs of thyrotoxicosis.

"DR Joffroy may validate symptoms"

Dalrymple sign:- rim of sclera is seen all around the cornea, on looking straight forward.
Rosenbach's sign:- fine tremor of the upper eyelids on slight closure of the eye.
Joffroy's sign:-lack of wrinkling of the forehead when a patient looks upward.
Moebius sign:- lack of convergence on looking to near object.
Von Graefe's sign (lid lag sign):-lagging of the upper eyelid on looking downward without movinh the head.
Stellwag's sign:-staring look with infrequent blinking.

Dr Ibrahim,,

- Causes of gynecomastia.

2011-08-07T11:57:00.001+02:00

Causes of gynecomastia.
Gynecomastia.

Genetic : klinefelter syndrome.
Young boy (puberty): due to transient increase of plasma estradiol.
Neonate: due to persistent maternal or placental lactogens.
Estrogen and estrogen like drugs (e.g. digitalis).
Cirrohosis,Cimetidine,Cytotoxic drugs.
Old age(due to conversion of androgen to estrogen in extra glandular tissue),Overactive thyroid (Hyperthyroidism)
Myxedema,Marijuana.
Acromrgally.
Spironolactone,Steroids.
Tumour (e.g. testis,adrenal,bronchogenic carcinoma).
INH,Iron deposition in testis.
Alcoholism.

- Gallbladder stone and surgery.

2011-07-19T06:39:00.000+02:00

Gallbladder stone and surgery.

video shows normal function of gallbladder and then problems from gallstones and how laparoscopic surgery is done to remove gallbladder.

- Drugs interfering with woman sexual functioning.

2011-07-03T00:06:00.000+02:00

Drugs interfering with woman sexual functioning.

"On batch"

Oral contraceptives.
Narcotics.

Barbiturates.
Benzodiazepine.

Antihypertensives.
Antipsychotics.
Antidepressants.
Antihistaminics.
Amphetamines.

Thiazide diuretics.
Cocaine.
Hallucinogens.

Dr Ibrahim

- Assessment of 2ry amenorrhea algorithm.

2011-07-01T10:25:00.004+02:00

Assessment of 2ry amenorrhea algorithm