I do not need Prozac... But let me learn how Fluoxetine works!

Fluoxetine: Sold as Prozac, Sarafem, Fontex etc.

Image Courtesy: "Depressants ." Human Diseases & Conditions. N.p., 2011. Web. 16 Feb. 2011.

This is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class

Fluoxetine is approved for the treatment of 

Major depression (including pediatric depression),

Obsessive-compulsive disorder (in both adult and pediatric populations), 

Bulimia nervosa, 

Panic disorder and 

Premenstrual dysphoric disorder.

Fluoxetine's mechanism of action is primarily that of an SSRI. 

SSRIs are believed to increase the extracellular level of the neurotransmitter serotonin by inhibiting its reuptake into the presynaptic cell, increasing the level of serotonin in the synaptic cleft available to bind to the postsynaptic receptor.

The bioavailability of fluoxetine is relatively high (72%), and peak plasma concentrations are reached in 6 to 8 hours. 

Fluoxetine is metabolized in the liver by isoenzymes of the cytochrome P450 system, including CYP2D6. The role of GYP in the metabolism of fluoxetine may be clinically important, as there is great genetic variability in the function of this enzyme among people. Only one metabolite of fluoxetine, norfluoxetine (N-demethylated fluoxetine), is biologically active. Steady concentration in the blood is achieved only after four weeks The brain concentration of fluoxetine and its metabolites keeps increasing through at least the first five weeks of treatment. That means that the full benefits of the current dose a patient receives are not realized for at least a month since its initiation Likewise, complete excretion of the drug may take several weeks.

Video: Youtube

HbA1c and Estimated Average Glucose (eAG)

Source of this information: ADA and http://www.ngsp.org/A1ceAG.asp


There is a very predictable relationship between HbA1c and AG. 
Understanding this relationship can help patients with diabetes and their health-care providers set day-to-day targets for AG based on HbA1c goals
Fasting glucose should be used with caution as a surrogate measure of AG. 
Finally, it is important to remember that HbA1c is a weighted average of glucose levels during the preceding 4 months. Unless the patient’s glucose levels are very stable month after month, quarterly measurement is needed to insure that a patient's glycemic control remains within the target range. 

How does HbA1c relate to average glucose (AG)?

In the Diabetes Control and Complications Trial or DCCT (New Engl J Med 1993;329:977-986) study of patients with Type 1 diabetes, quarterly HbA1c determinations were the principal measure of glycemic control; study subjects also performed quarterly 24-hour, 7-point capillary-blood glucose profiles. 

Blood specimens were obtained by subjects in the home setting, pre-meal, 90 minutes post-meal, and at bed-time. In an analysis of the DCCT glucose profile data (Diabetes Care 25:275-278, 2002), mean HbA1c and AG were calculated for each study subject (n= 1439). Results showed a linear relationship between HbA1c and AG 

(AG(mg/dL) = ( 35.6 x HbA1c ) - 77.3), with a Pearson correlation coefficient (r) of 0.82.

CALCULATOR: The following link will help to do the Estimated Average Glucose Calculation

http://professional.diabetes.org/GlucoseCalculator.aspx :

HbA1c (%)	eAG (mg/dL)	eAG (mmol/l)
5	97	5.4
6	126	7.0
7	154	8.6
8	183	10.2
9	212	11.8
10	240	13.4
11	269	14.9
12	298	16.5

HbA1C - The new way of measuring it - IN future!!

There have been multiple attempts in Global Standarizations and consensus statements have been issued, but very difficult to implement.
In the US we still follow HbA1c in % and eAG ( estimated average glucose) is just catching up.
US guidelines developed based on he National Glycohemoglobin Standardization Program (NGSP)
Two major measurement criteria:  International Federation of Clinical Chemistry (IFCC) units vs NGSP 

IFCC-HbA1c	DCCT- HbA1c	Mono S- HbA1c
(mmol/mol)	(%)	(%)
10	3.1	2.0
20	4.0	2.9
30	4.9	3.9
40	5.8	4.8
45	6.3	5.3
50	6.7	5.8
55	7.2	6.3
60	7.6	6.8
65	8.1	7.2
70	8.6	7.7
80	9.5	8.7
90	10.4	9.6
100	11.3	10.6

The International Diabetes Federation and American College of Endocrinology recommend HbA_1c values below 48 mmol/mol (6.5%), while American Diabetes Association recommends that the HbA_1c be below 53 mmol/mol (7.0%) for most patients.^[

2010 Consensus Statement on the Worldwide Standardization of HbA1c

The recommendations are:

1. HbA1c test results should be standardized worldwide, including the reference system and results reporting.
2. The IFCC reference system for HbA1c represents the only valid anchor to implement standardisation of the measurement.
3. HbA1c results are to be reported by clinical laboratories worldwide in SI (Système International) units (mmol/mol – no decimals) and derived NGSP units (% - one decimal), using the IFCC-NGSP master equation (DCCT units).
4. HbA1c conversion tables including both SI (IFCC) and NGSP units should be easily accessible to the diabetes community.
5. Editors of journals and other printed material are strongly recommended to require that submitted manuscripts report HbA1c in both SI (IFCC) and NGSP/DCCT units.
6. The reportable term for glycated hemoglobin is HbA1c, although other abbreviations may be used in guidelines and educational material (A1C).

History of HbA1c and what does it do?

History:
Hemoglobin A1c was first separated from other forms of hemoglobin by Huisman and Meyering in 1958.  It was first characterized as a glycoprotein by Bookchin and Gallop in 1968. Its increase in diabetes was first described in 1969 by Samuel Rahbar The use of hemoglobin A1c for monitoring the degree of control of glucose metabolism in diabetic patients was proposed in 1976 by Anthony Cerami, Ronald Koenig and coworkers.

N-linked protein glycosylation (N-glycosylation of N-glycans) at Asn residues (Asn-x-Ser/Thr motifs) in glycoproteins.


What are Glycoproteins? 
They are proteins that contain oligosaccharide chains (glycans) covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational orposttranslational modification. This process is known as glycosylation. In proteins that have segments extending extracellularly, the extracellular segments are often glycosylated. Glycoproteins are often important integral membrane proteins, where they play a role in cell–cell interactions. Glycoproteins are also formed in the cytosol, but their functions and the pathways producing these modifications in this compartment are less well understood


Why do we measure HbA1c every 3 months?

In the normal 120-day lifespan of the red blood cell, glucose molecules react with hemoglobin, forming glycosolated hemoglobin. In individuals with poorly controlled diabetes, the quantities of these glycosolated hemoglobins are much higher than in healthy people.

Once a hemoglobin molecule is glycosolated, it remains that way. A buildup of glycosolated hemoglobin within the red cell, therefore, reflects the average level of glucose to which the cell has been exposed during its life-cycle. Measuring glycosolated hemoglobin assesses the effectiveness of therapy by monitoring long-term serum glucose regulation. The HbA_1c level is proportional to average blood glucose concentration over the previous four weeks to three months. Some researchers state that the major proportion of its value is related to a rather shorter period of two to four weeks.

Image source: http://adiscar-adiscar.blogspot.com

We will talk about measuring HbA1c tomorrow

Tummy Tuck and Stretch Marks!

Medical Term for Strech Marks: Striae
Stretch marks or striae (singular stria), are a form of scarring on the skin with an off-color hue. They are caused by tearing of the dermis, which over time may diminish, but will not disappear completely.
Stretch marks are often the result of the rapid stretching of the skin associated with rapid growth.
Stretch marks can appear anywhere on the body, but are most likely to appear in places where larger amounts of fat are stored. Most common places are the abdomen, breasts, upper arms, underarms, back, thighs , hips, and buttocks. They pose no health risk in and of themselves.


In CUSHING SYNDROME, the glucocorticoid hormones responsible for the development of stretch marks affect the dermis by preventing the fibroblasts from forming collagen and elastin fibers, necessary to keep rapidly growing skin taut. This creates a lack of supportive material, as the skin is stretched and leads to dermal and epidermal tearing.
A new modality, fractional laser resurfacing, offers a novel approach to treating striae. Using scattered pulses of light only a fraction of the scar is zapped by the laser over the course of several treatments. This creates microscopic wounds. The body responds to each treatment by producing new collagen and epithelium

Picture courtesy: Derm Atlas

Abdominoplasty or "tummy tuck" is a cosmetic surgery procedure used to make the abdomen more firm. The surgery involves the removal of excess skin and fat from the middle and lower abdomen in order to tighten the muscle and fascia of the abdominal wall. 

Epistaxes ( Nose bleeds) - Anterior Nose bleed

This is probably one of the scariest medical problem a parent or even an adult experiences and many a times it is innocuous.
Cause is local or generalized (systemic)

Broadly divided to Anterior and Posterior nose bleeds.

Today the discussion will be anterior nose bleeds

Nosebleeds begin in the lower part of the septum, (wall that separates the two nostrils ). The septum has tiny blood vessels that can break by nose blowing or nose picking. Nosebleeds coming from the front of the nose,  (anterior nosebleeds) often begin with blood out one nostril usually when sitting or standing.

Anterior nosebleeds are common during dry climates or during the winter when dry, heated indoor air dehydrates the nasal membrane. Dryness result in crusting, cracking, and finally bleeding. 

This bleeding can be prevented by placing a slight application of petroleum jelly or an antibiotic ointment on the end of a fingertip and then rubbing it inside the nose, especially on the septum.

ADVISE TO STOP BLEEDING

Stay calm, or help the child (or the adult) to calm down. Agitation makes bleeding more profuse.

Keep head higher than the level of the heart. Sit up.
Leaning slightly forward helps the blood not going into the throat
Gently blow any clotted blood out of the nose.  Nasal decongestant spray can help.

Using the thumb and index finger, pinch all the soft parts of the nose.  

Do not pack the inside of the nose with gauze or cotton.
Hold the position for five minutes. 

If bleeding persists, hold an additional 10 minutes.

Here is the first aid demo: from YOUTUBE

Surgical procedure for severe nose bleeding

Respiratory Syncytial Virus - How to prevent my severity?

How can I help prevent the spread of RSV?

RSV is spread by coming in close contact with an infected person and the droplets produced when the person coughs or sneezes.  Careful hand washing with soap and warm water is the best way to prevent the spread of RSV. 

Palivizumab (brand name Synagis) is a monoclonal antibody produced by recombinant DNA technology. It is used in the prevention of respiratory syncytial virus (RSV) infections. It is recommended for infants that are high-risk because of prematurity or other medical problems such as congenital heart disease.

Palivizumab is a humanized monoclonal antibody (IgG) directed against an epitope in the A antigenic site of the F protein of RSV. Palivizumab reduced the risk of hospitalization due to RSV infection by 55%. Palivizumab is dosed once a month via intramuscular (IM) injection, to be administered throughout the duration of the RSV season.

Palivizumab targets the fusion protein of RSV, inhibiting its entry into the cell and thereby preventing infection.

The American Academy of Pediatrics (AAP) has published recommendations for the use of palivizumab. Updated AAP recommendations were published in 2009. Palivizumab  is used only for prevention, not for treatment, and once initiated for a given RSV season (usually November–March), it should be continued for the full duration of that season.

Reasons to consider palivizumab prophylaxis include:

Prematurity

• ≤ 28 weeks gestation and < 12 months of age at the start of RSV season
• 29-32 weeks gestation and < 6 months of age at the start of RSV season
• 32-35 weeks gestation and < 3 months of age at the start of RSV season, if there is a risk factor (child care attendance or sibling younger than 5 years old)

Chronic lung disease of prematurity

• Chronic lung disease still requiring oxygen/medication, for the first and second RSV seasons
• Chronic lung disease that required oxygen/medication within the 6 months preceding RSV season, for the first RSV season

Congenital heart disease

• Cyanotic heart disease, for the first 24 months of life
• Moderate to severe pulmonary hypertension, for the first 24 months of life
• Congestive heart failure requiring medication, for the first 24 months of life
• Children who have undergone open heart surgery during RSV season, for one additional dose after cardiopulmonary bypass (only if they still meet one of the other criteria)

Other conditions where prophylaxis might be considered but inadequate data is available:

• Immunocompromise
• Cystic fibrosis

Of note, a course of palivizumab is quite expensive, and the above recommendations were written based on estimates of its overall cost-effectiveness for preventing severe RSV disease.

Who am I and why should you be scared of me now?

I am a very common virus that leads to mild, cold-like symptoms in adults and older healthy children. But I am bad with young babies. Most infants have been infected by me before their second birthday.
I love the season from October to Spring (my season!)

More severe  disease with me may occur in the following infants:

• Premature infants
• Infants with chronic lung disease
• Immunodeficient infants
• Infants with heart disease

The following increase the risk for being affected by me:

• Day care
• Tobacco smoke
• Having school-aged brothers or sisters
• Crowded conditions
  
  
  You get to know about me 4 - 6 days after coming in contact with me.
  Antibiotics cannot make me go away
  If am nice (mild) I go away without treatment.
  Infants and children with a severe infection with me will be in the intensive care unit. Treatment will include:
  • Oxygen ( may need a ventilator)
  • humidified air
  • IV fluids
  
  I AM Respiratory Syncytial Virus
  Belonging to the Paramyxoviridae, I am virus in an enveloped, spherical, negative-strand RNA virus measuring 120-300 nm
  
  
  Diagnosis: You can find me by a direct immunofluorescence test for RSV antigen , and is reported to be 90% sensitive as compared to culture. RSV antigen may appear in the cytoplasm of cells within 8 hours of infection. Viral culture is performed in conjunction with the antigen test. The only acceptable specimen to detect me is a nasopharyngeal aspirate collected in viral transport media.
  Tomorrow I will tell you how to avoid me!!
  Source of picture and some text: http://pathology5.pathology.jhmi.edu/micro/v20n47.htm