DOWN SYNDROME

 DEFINITION 

two days ago Mbah Dukun Bagong visit his hometown, he met his old friend, he saw his friend's daughter. her face look freaky, like mongoloid face, whats wrong with her?

Down Syndrome, Trisomy 21 or Mongolism, was first described by Dr. Langdon Down in 1865. At that time, the diagnosis of the syndrome was based solely on physical findings. Down syndrome isn't a disease. Down Syndrome is a genetic condition. As the word syndrome implies, it is a collection of common characteristics that is evident not only physically, but also by a degree of learning disability.



ETIOLOGY
Down syndrome is usually caused by an error in cell division called "nondisjunction."  Nondisjunction results in an embryo with 3 copies of chromosome 21 instead of the usual two.  Prior to or at conception, a pair of 21st chromosomes in either the sperm or the egg fails to separate.  As the embryo develops, the extra chromosome is replicated in every cell of the body.  This type of Down syndrome, which accounts for 95% of cases, is called Trisomy 21.
Chromosomes are in simple terms the ‘building blocks’ that give us our individual characteristics, for example, blue eyes, blonde hair etc. Similarly, people with Down Syndrome, who share this extra chromosome, also share common physical features.
Note, the number and structure of chromosomes within an individual cell is referred to as the karyotype of a cell. The term mongolism, mongoloid or mongoloid idiot are outdated and stigmatizing terms and should not be used to describe persons with this condition. The etiology of Down Syndrome relates to the problem of nondisjunction of a 21 chromosome during oogenesis, thus an extra 21 chromosome is provided to the offspring by the mother. Recent studies also implicate paternal etiology through nondisjunction during spermatogenesis.



TYPES of DOWN SYNDROME
There are 3 types of Down Syndrome, although it is generally thought that there is no clinical difference in the three genotypes.
(1) Trisomy 21 (94%): The extra 21 chromosome (three instead of the usual two) produces a complement of 47 chromosomes. Trisomy 21 may also be referred to as Trisomy G.
(2) Translocation (5%): A segment of a 21 chromosome is found attached to other pairs of  chromosomes (usually #14, thus referred to as a 14/21 translocation). These individuals have the normal complement of 46 chromosomes.
(3) Mosaicism (1%): Nondisjunction occurs at a later stage of cell division, therefore, some cells have the normal complement of 46 chromosomes and other cells 47 chromosomes (with an extra 21 chromosome).

The two other types of Down syndrome are called mosaicism and translocation.  Mosaicism occurs when nondisjunction of chromosome 21 takes place in one-but not all-of the initial cell divisions after fertilization.  When this occurs, there is a mixture of two types of cells, some containing the usual 46 chromosomes and others containing 47.  Those cells with 47 chromosomes contain an extra chromosome 21.  Mosaicism accounts for about 1% of all cases of Down syndrome.  Research has indicated that individuals with mosaic Down syndrome may have fewer characteristics of Down syndrome than those with other types of Down syndrome.  However, broad generalizations are not possible due to the wide range of abilities people with Down syndrome possess.
 Translocation accounts for about 4% of all cases of Down syndrome.  In translocation, part of chromosome 21 breaks off during cell division and attaches to another chromosome, typically chromosome 14.  While the total number of chromosomes in the cells remain 46, the presence of an extra part of chromosome 21 causes the characteristics of Down syndrome.
Regardless of the type of Down syndrome a person may have, all people with Down syndrome have an extra, critical portion of chromosome 21 present in all or some of their cells.  This additional genetic material alters the course of development and causes the characteristics associated with Down syndrome. 
The cause of nondisjunction is currently unknown, but research has shown that it increases in frequency as a woman ages.  However, due to higher birth rates in younger women, 80% of children with Down syndrome are born to women under 35 years of age.  There is no definitive scientific research that indicates that Down syndrome is caused by environmental factors or the parents' activities before or during pregnancy.
 Once a woman has given birth to a baby with Trisomy 21, it is estimated that her chances of having another baby with Trisomy 21 is 1% greater than her chances by age alone.
The age of the mother does not seem to be linked to the risk of translocation.  Most cases are sporadic-that is, chance events.  However, in about one third of cases, one parent is a carrier of a translocated chromosome.  The risk of recurrence of translocation is about 3% if the father is the carrier and 10-15% if the mother is the carrier.  Genetic counseling can determine the origin of translocation. 

SYMPTOMS and SIGNS 

What are the characteristic features and symptoms of Down syndrome?
Although the severity of Down syndrome ranges from mild to severe, most individuals with Down syndrome have widely recognizable physical characteristics. These include:
•    a flattened face and nose, a short neck, a small mouth sometimes with a large, protruding tongue, small ears, upward slanting eyes that may have small skin folds at the inner corner (epicanthal fold);
•    white spots (also known as Brushfield spots) may be present on the colored part of the eye (iris);
•    the hands are short and broad with short fingers, and with a single crease in the palm;
•    poor muscle tone and loose ligaments are also common; and
•    development and growth is usually delayed and often average height and developmental milestones are not reached.

 

DIAGNOSIS

How is Down syndrome Diagnosed?
A. Prenatally
There are two types of tests for Down syndrome that can be performed before a baby is born: screening tests and diagnostic tests. Prenatal screens estimate the chance of the fetus having Down syndrome. These tests only provide a probability. Diagnostic tests can provide a definitive diagnosis with almost 100% accuracy.
 Most screening tests involve a blood test and an ultrasound (sonogram). The blood tests (or serum screening tests) measure quantities of various substances in the blood of the mother. Together with a woman's age, these are used to estimate her chance of having a child with Down syndrome. These blood tests are often performed in conjunction with a detailed sonogram to check for "markers" (characteristics that some researchers feel may have a significant association with Down syndrome). Recently, researchers have developed a maternal serum/ultrasound/age combination that can yield a much higher accuracy rate at an earlier stage in the pregnancy. Still, the screen will not definitively diagnose Down syndrome.
 Prenatal screening tests are now routinely offered to women of all ages. If the chance of having a child with Down syndrome is high from prenatal screening, doctors will often advise a mother to undergo diagnostic testing if they desire a definitive diagnosis.
The diagnostic procedures available for prenatal diagnosis of Down syndrome are chorionic villus sampling (CVS) and amniocentesis. These procedures, which carry up to a 1% risk of causing a spontaneous termination (miscarriage), are practically 100% accurate in diagnosing Down syndrome. Amniocentesis is usually performed in the second trimester after 15 weeks of gestation, CVS in the first trimester between 9 and 11 weeks. 

B. At Birth
Down syndrome is usually identified at birth by the presence of certain physical traits: low muscle tone, a single deep crease across the palm of the hand, a slightly flattened facial profile and an upward slant to the eyes.  Because these features may be present in babies without Down syndrome, a chromosomal analysis called a karyotype is done to confirm the diagnosis. To obtain a karyotype, doctors draw a blood sample to examine the baby's cells. They use special tools to photograph the chromosomes and then group them by size, number, and shape. By examining the karyotype, doctors can diagnose Down syndrome.  Another genetic test called FISH can apply similar principles and confirm a diagnosis in a shorter amount of time.

MANAGEMENT

Can a baby with Down syndrome be cured?
There is no cure for a child born with this condition but many symptoms can be treated and special early intervention programs are enabling these individuals to develop to their potential.
A child with Down syndrome can usually do most things that any young child can do such as walking, talking, dressing and being toilet trained although they may do these things later than other children.
How is Down syndrome managed?
Although the genetic cause of Down syndrome is known, there is currently no cure. Due to advances in technology, scientists are slowly beginning to understand which genes when present in three copies are responsible for which Down syndrome characteristics, but it will take many years to fully grasp the complex interplay between the different genes. Much research to date is focused on understanding the causes of impaired cognition in Down syndrome and on finding potential therapies that might improve learning. Most of these studies are carried out using animal models of Down syndrome, but some human clinical trials involving potential therapies are also being conducted.
Corrective surgery for heart defects, gastrointestinal irregularities, and other health issues is necessary for some individuals. Regular health checkups should be scheduled to screen for other conditions such as visual impairments, ear infections, hearing loss, hypothyroidism, obesity, and other medical conditions. Individuals with Down syndrome should be fully included in family and community life

Who is at risk of having a child with Down syndrome?
In an individual with Down syndrome, the extra copy of chromosome 21 can come from either the egg or the sperm. It has been shown, however, that as a woman gets older, her chance of having a child with Down syndrome increases, as shown in. In particular, a woman who is 35 years or older at the time of delivery of her baby, has an increased chance of having a baby with Down syndrome.

CONDYLOMA ACUMINATA

DESCRIPTION

Genital warts or condyloma acuminata are warty growths that can be found on the labia, vagina, and cervix as well as in, and around the anal area, the external urethral opening or in the bladder. Men may also have condyloma on the penis and scrotum, in and around the anal opening, and in the urethra. Condyloma are caused by the Human Papilloma Virus (HPV).


There are about 45 strains of this virus, and 5 types are known to cause pre-cancerous or cancerous changes. At present it is not possible to tell from a biopsy specimen which specific type of the virus a given patient has, but the biopsy will at least tell if there are pre-cancerous or cancerous changes present. Condyloma are usually transmitted sexually, that is, passed through direct sexual contact with someone who has the warts. There are certain strains of the virus which are not necessarily sexually transmitted; that is, they may be contracted merely by getting the virus on your hands and then transmitting it to the genital area. All sexual partners need to be examined to rule out the virus. The male partner has a 70% chance of having warts after repeated sexual relations with an infected female partner.


History
* Smoking, oral contraceptives, multiple sexual partners, and early coital age are risk factors for acquiring condyloma acuminata.

* Generally, two thirds of individuals who have sexual contact with a partner with condyloma acuminata develop lesions within 3 months.
* The chief complaint usually is one of painless bumps, pruritus, or discharge.
          o Involvement of more than 1 area is common.
          o History of multiple lesions, rather than 1 isolated wart, is common.
* Oral, laryngeal, or tracheal mucosal lesions (rare) presumably are transferred by oral-genital contact.
* History of anal intercourse in both males and females warrants a thorough search for perianal lesions.
* Rarely, urethral bleeding or urinary obstruction may be the presenting complaint when the wart involves the meatus.
* The patient's history may indicate presence of previous or other current STDs.
* Coital bleeding may occur. Vaginal bleeding during pregnancy may be due to condyloma eruptions.
* Latent illness may become active, particularly with pregnancy and immunosuppression.
* Lesions may regress spontaneously, remain the same, or progress.
* Pruritus may be present.
* Discharge may be a complaint.

Physical
* Single or multiple papular eruptions may be observed.
          o Eruptions may appear pearly, filiform, fungating, cauliflower, or plaquelike.
          o They can be quite smooth (particularly on penile shaft), verrucous, or lobulated.
          o Eruptions may seem harmless or may have a disturbing appearance.
* Carefully search for simultaneously involved multiple sites.
* Eruptions' color may be the same as the skin, or they may exhibit erythema or hyperpigmentation. Check for irregularity in shape, form, or color suggestive of melanoma or malignancy.
* Propensity has been established for penile glans and shaft in men and for vulvovaginal and cervical areas in women.
          o In contrast to early reports, presence of external condyloma acuminata in both men and women warrants a thorough search for cervical or urethral lesions.
          o Such internal lesions have been found in more than one half of females with external lesions.
          o One report indicates that infected males have a 20% chance of having subclinical urethral lesions.
          o More than 50% of female patients with external lesions have been found to have negative Papanicolaou (Pap) tests but tested positive for HPV infection using in situ hybridization.
* Urethral meatus and mucosal lesions can occur.
          o Some are subclinical.
          o Hair or the inner aspect of uncircumcised foreskin hides some lesions.
* Search for evidence of other STDs (eg, ulcerations, adenopathy, vesicles, discharge).
* Look for perianal lesions, particularly in patients with history or risk of immunosuppression or anal intercourse.

Causes

* Several of the epidermotropic human papillomaviruses (HPVs) cause condyloma acuminata.
* HPV types 6 and 11 most commonly are isolated, but many of the more than 60 types of HPV potentially cause condyloma.
* Male sexual partners of women with cervical intraepithelial neoplasia often have infections with the same viral type.



INCUBATION

Warts usually appear within three weeks to six months after contact with an infected person, although there have been reports of warts appearing as long as two or more years after contact. Some persons have naturally good immune systems so not everyone who has been exposed to venereal warts will develop them.

DIAGNOSIS

Warts may appear as single entities or form cauliflower-like clusters. In this case, the patient usually recognizes that something is wrong. Warts may also have the appearance of tiny fingerlike projections on the vagina or vulva, or may appear as a flat, roughened area of the vulva, vagina, or cervix. These are so small that even the physician may not see them unless he uses a magnifying instrument called a colposcope. Most persons do not have symptoms with warts, but if they do the most frequent problems are mild itching and a watery vaginal and they are treated with appropriate medication after the discharge has been evaluated. The diagnosis of warts is made by visual examination with a colposcope (a magnifying device) and by a biopsy (a piece of tissue that is removed and sent to a pathologist) of suspicious areas. Pap smears may suggest that there are abnormal cells due to condyloma on the cervix, but biopsy is the only definitive test.



Pathophysiology

Cells of the basal layer of the epidermis are invaded by human papillomavirus (HPV). These  penetrate through skin and cause mucosal microabrasions. A latent viral phase begins with no signs or symptoms and can last from a month to several years. Following latency, production of viral DNA, capsids, and particles begins. Host cells become infected and develop the morphologic atypical koilocytosis of condyloma acuminata.
The most commonly affected areas are the penis, vulva, vagina, cervix, perineum, and perianal area. Uncommon mucosal lesions in the oropharynx, larynx, and trachea have been reported. HPV-6 even has been reported in other uncommon areas (eg, extremities).
Multiple simultaneous lesions are common and may involve subclinical states as well-differentiated anatomic sites. Subclinical infections have been established to carry both an infectious and oncogenic potential.
Consider sexual abuse as a possible underlying problem in pediatric patients;2 however, keep in mind that infection by direct manual contact or indirectly by fomites rarely may occur. Finally, passage through an infected vaginal canal at birth may cause respiratory lesions in infants

Mortality/Morbidity

    * Mortality is secondary to malignant transformation to carcinoma in both males and females. This oncogenic potential has been reported to triple the risk of genitourinary cancer among infected males. Fortunately, this is rare with HPV types 6 and 11, which are the most commonly isolated viruses.
    * HPV infection appears to be more common and worse in patients with various types of immunologic deficiencies. Recurrence rates, size, discomfort, and risk of oncologic progression are highest among those patients. Secondary infection is uncommon.
    * Latent illness often becomes active during pregnancy. Vulvar condyloma acuminata may interfere with parturition. Trauma then may occur, producing crusting or erythema. Bleeding has been reported in large lesions that can occur during pregnancy.
    * In males, bleeding has been reported due to flat warts of the penile urethral meatus, usually associated with HPV-16. Lesions may lead to disfigurement of area(s) involved. Finally, acute urethral obstruction in women also may occur.




CONDYLOMA AND PREGNANCY

Warts during pregnancy usually increase in size due to the increase in hormone levels and the increased vaginal moisture. Treatment depends upon the size and location of the warts. Your physician will keep close watch on them during your pregnancy. There is a rare chance that if warts are in the vagina and on the cervix during labor and delivery, that the baby could inhale the condyloma virus and later develop nodules in the nasopharynx and on the vocal cords. This can be evaluated by doing laryngoscopy and treated if necessary.



TREATMENT OPTIONS

1. Trichloracetic acid (TCA) : This is a strong chemical that causes a very superficial burn, which in turn causes the top layer of skin to peel off. This is usually only used on the vulvar (outside) area and can be repeated every 10-14 days for 3-4 times. Upon application, the acid causes significant discomfort that lasts 3-5 minutes, then subsides. The medication does not have to be washed off. Two to four days after application, the top layer of skin will peel and the underlying area will be mildly sore. Keep the area cool and dry. TCA is more effective for raised warts than for flat ones.

2. Efudex Cream: Efudex or 5FU, is a strong anticancer cream that is prescribed for women with vaginal condyloma. The cream is placed into the vagina for five consecutive nights and causes a sloughing of the top layer of skin in the vagina. The cream is very irritating to the outside of the vulva so care must be taken to keep the labia coated with Vaseline or A&D ointment. If this treatment is used, a separate hand out will be given to you that explains proper usage.

3. Cryosurgery: This technique uses a cold probe that freezes the wart. As the wart freezes, fluid is lost which causes cell destruction. As the warts drop off there may be a watery discharge that lasts a few weeks. Cryo is especially useful in large, cauliflower-like warts. Each wart is treated for 30-60 seconds depending on size and requires no anesthesia.

4. Laser: Laser is a strong beam of concentrated light that evaporates tissue. Laser treatment is used for warts that have not responded to office therapies or when there is extensive involvement of the cervix, vagina and vulva. When warts are small they can be treated in the office using local anesthesia. When warts are extensive, laser is done as out patient surgery in the hospital with either general or regional anesthesia. Laser has the advantage of causing virtually no scar tissue. Laser therapy is also a very accurate treatment because the beam of light is directed through the colposcope, thus the physician is able to treat every wart that is visible. If you have laser therapy, you will be given a separate handout that describes the procedure, the risks and benefits, and postoperative care.

5. Watch: If the pap smear is normal and biopsies show only condyloma, some patients will choose not to be treated. As some of the strains of the wart virus cause pre-cancerous and cancerous changes, strict adherence to follow-up is mandatory: pap smears and colposcopy must be done every three months.

If office therapy is used, the urethra and bladder base must be evaluated by urethroscopy and the anal canal by anoscopy to determine if warts are in these locations. Mild discomfort may occur after any of these treatments, but will generally not last longer than a day or two (except extensive vulvar laser). It is important to keep all follow-up visits as warts that you can not see with the eye may remain or reappear. After the condyloma have been treated, they may recur without re-exposure, so you need to be checked monthly for six months. Other treatments are used for condyloma (podophyllin, excision, cautery and liquid nitrogen), but we have the best results with the treatments described above.

SELF CARE

By following the instructions below and keeping a positive attitude, you will give yourself the best possible care during your recovery from venereal warts.
1. Keep the areas clean and dry: The virus grows rapidly in warm, moist areas, so wear cotton underwear, loose clothing, and use a hairdryer on a low setting to dry the vulva after a bath or shower.
2. Sitz Baths: Soaking in a warm tub of water, especially after a treatment, will soothe the area, decrease the pain, and promote healing. After the bath, dry the area well with a hairdryer on a low setting.
3. Vaginal Infections: Vaginal infections may help the wart virus grow and spread. If you have a discharge that has a bad odor, or if you have itching or burning of the vulvar/vaginal area, make an appointment for evaluation.
4. Stay Healthy : Overall wellness can be achieved by eating nutritious meals, getting plenty of rest, and by reducing stress as much as possible. For those whose diets consist primarily of “junk” and “fast foods”, you may choose to supplement your diet with some vitamins: a general multiple vitamin, a B complex, 1,000 mg of vitamin C and 400 iu of vitamin E per day. Decreasing or stopping smoking will also enhance your overall wellness. 5. Intercourse: While the warts are present, you may wish to abstain from intercourse. The virus is very contagious. Small undetectable warts may be shedding viral particles, and sexual contact may spread the virus into the vagina or onto the cervix. Remember, there are other ways to make love besides intercourse.

6. Condoms: If you do have intercourse while the warts are present in either partner, use a condom. However, the condom may not offer complete protection for the transmission of  condyloma. As it only covers the penis, the male could still get warts on the scrotum, and if he has them on the scrotum, the female could get the warts on her vulva. It is advisable to continue the use of condoms for at least three months after both partners are clear of warts. Condoms also have the advantage of protection against gonorrhea, chlamydia, AIDS and herpes. Their use is encouraged when you are starting new relationships.

GONORRHEA

DEFINITION

Gonorrhea is a disease of sexually transmitted infections (STI) caused by the bacterium Neisseria gonorrhoeae, gram negative bacteria diplokokkus who made man as the intermediary. For several centuries, a variety of names have been used to describe infections caused by N.




This gonorrhoeae, including; 'strangury' used by Hippocrates, the naming of gonorrhea itself given by Galen (130 BC) to describe the nature of urethral exudate as the tears flow (flow of seed) and M. Neisser, introduced by Albert Neisser, who discovered it in 1879 micro-organisms from staining smears taken from the vagina, urethra and conjunctival exudate.
Cultures of bacterial N. gonorrhoeae was first reported by Leistikow and Löffler in 1882 and was developed in 1964 by Thayer and Martin, who found a selective culture medium for special. Thayer-Martin media is selective media to isolate gonokok. Containing vancomycin to suppress growth of Gram-positive bacteria, kolimestat to suppress the growth of Gram-negative bacteria and nystatin to suppress the growth of fungi.
In most cases of transmission through unprotected sex is a genito-genital, oro-genital and ano-genital. But in addition it can also occur manually through the tools, clothing, towels, thermometer.
N. gonorrhoeae knows no racial, social, economic or geographical conditions. Men, women both adults and children can be infected with this disease. The global spread of this infection is supported by human habits that helped the move to increase resistance factor.


EPIDEMIOLOGY
The infection is transmitted through sexual intercourse, can also be transmitted to the fetus during the birth process in progress. Although all groups vulnerable to infection of this disease, but its highest incidence in the age range 15-35 years. Among the female population in 2000, the highest incidence occurred at age 15 -19 years (715.6 per 100,000) opposite to the male average of the highest incidence occurred at age 20-24 years (589.7 per 100,000).
N. Epidemiology gonorrhoeae is different in each - each developing country. In Sweden, the incidence of gonorrhea reported 487/100.000 as many people who suffer in 1970. In 1987, reportedly as many as 31/100.000 people who suffer, in 1994 reported gonorrhea patients declining at only about 31/100.000 people who suffer.
In the United States, the incidence of gonorrhea cases decreased. In 1975 reported 473/100.000 people who suffer, where the figures show that cases of gonorrhea in the United States has decreased until 1984.
Risk factors:
- Sexual relations with patients without protection
- Have many sexual partners
- In infants - while passing through the birth from an infected mother
- In children - sexual abuse (sexual abuse) by the infected patient.

ETIOLOGY
N. gonorrhoeae is a bacteria that can not move, no spores, types of gram-negative diplococcus with size from 0.8 to 1.6 micro. Gonococcus bacteria are not resistant to moisture, which tends to affect sexual transmission.
These bacteria are resistant to oxygen but usually requires 2-10% in growth in atmospheric CO2. These bacteria need iron to grow and get it through transferrin, lactoferrin and hemoglobin. These organisms can not live in dry areas and low temperatures, grows optimally at 35-37o and pH 7.2 to 7.6 for optimal growth.
Gonococcus consists of 4 morphology, type 1 and 2 are pathogenic and type 3 and 4 non-pathogenic. Type 1 and 2 have pili that are virulent and there on the surface, while type 3 and 4 do not have filli and non-virulent. Pili will be attached to the mucosal epithelium and will cause an inflammatory reaction.

Neisseria Gonorrhoeae

PATHOGENESIS
Despite a considerable increase in knowledge about the pathogenesis of microorganisms, the exact molecular mechanisms of invasion gonococcus into the host cell remains unknown. There are several virulence factors involved in the mechanism of adhesion, and invasion of mucosal inflammation. Pili play an important role in the pathogenesis of gonorrhea. Pili enhance adhesion to host cells, which may be the reason why gonococcus who do not have pili are less able to infect humans. Antibodies antipili block epithelial adhesion and enhance the ability of phagocytic cells. Also note that the expression of transferrin receptor plays an important role and expression of full-length lipo-Oligosaccharides (LOS) appears necessary for maximal infection.
The area is most easily infected columnar epithelial area of the urethra and endocervix, glands and ducts parauretra in men and women, Bartolini glands, eye conjunctiva and rectum. Primary infection occurring in women who have puberty occurs in squamous epithelium of the vagina.

DIAGNOSIS
Gonorrhea incubation period is very short, varying between 2-10 days, occasionally longer, with most symptoms usually appear 2-5 days after being infected by patients. In a small number of cases can be asymptomatic for several months. Signs, symptoms and complications differ in men and women. Unknown 10% of men and 50% of women are asymptomatic.

In the male genitourinary tract can be found:
a. urethral infection in the urethra which usually cause discharge mukopurulen or purulent (> 80%) and / or dysuria (> 50%)
b. epidydymal unilateral tenderness and edema
c. anal infection: itching in the anal region
d. Oral infections: possible without symptoms or sore throat
At the bottom of the female genitourinary tract:
a. discharge mukopurulen or purulent cervical
b. discharge vagina or bleeding; vulvaginitis in children
At the top female genitourinary tract:
a. PID (Pelvic inflamatory Diseases)
b. lower stomach pain
c. fever
Other symptoms:
a. discharge who mukopurulen or purulent rectal
b. oropharyngeal-pharyngitis
c. purulent conjunctivitis eyes
d. GDI (Gonorrheal Disseminated Infection):
- Fever (usually <390c)> 45 kg: same as adult dose
c. Ciprofloxacin 500 mg orally as a single dose. In children not recommended.
The recommended treatment for gonorrhea clamidia accompanied by infection, because of the possibility of simultaneously clamidia infection with gonorrhea, patients were also given a single dose of azithromycin 1 gram or doxycycline 100 mg can be given for 7 days. For pregnant women, given erythromycin 500 mg 4 times daily for 7 days or if erythromycin not tolerated to diberian amoxicillin 500 mg 3 times daily for 7-10 days.
Treatment in special situations, for example:
a. Pregnant / lactating
In pregnant women can not be given drug class quinolones and tetracyclines. The recommended is the provision of cephalosporin class of drugs (Ceftriaxone 250 mg IM as single dose). If a pregnant woman is allergic to penicillin or cephalosporins can not be tolerated should be given Spektinomisin 2 g IM as single dose. In pregnant women can also be given Amoxicillin 2 g or 3 g orally with the addition of probenecid 1 g orally as a single dose given during isolation N. gonorrhoeae that are sensitive to penicillin. Amoxicillin is recommended fatherly treatment if accompanied by infection of C. trachomatis.
b. Disseminated Gonococcal Infection (DGI)
Given parenteral therapy 24-48 hours, after no improvement was replaced with oral regimens given for 1 week:
- Initial regimen given Ceftriaxone 1 g IM or IV per 24 hours
- Alternative regimens that can be given as follows:
§ Sefotaksim 1 g IV per 8 hours
§ Seftisoksim 1 g IV per 8 hours
§ Ciprofloxacin 400 mg IV per 12 hours
§ Olflosaksin 400 mg IV per 12 hours
§ levofloxacin 250 mg IV per 24 hours
§ Spektinomisin 2 g IM per 12 hours
- Oral regimen given after a repair:
§ cefixime 400 mg 2 times a day
§ Ciprofloxacin 500 mg 2 times a day
§ ofloxacin 400 mg 2 times a day
§ levofloxacin 500 mg once daily
c. Ophtalmia neonatorum
The recommended regimen is Ceftriaxone 25-50 mg / kg IV or IM as a single dose, dose no more than 125 mg.

COMPLICATIONS
Complications are:
a. urethra is scarred or spots on the possibility of leading to a decline in male fertility or bladder obstruction
b. grated or spots on the upper reproductive tract in women with PID (pelvic inflammatory disease) may lead to infertility, chronic pelvic pain and ectopic pregnancy
c. the possibility of premature birth, neonatal infection and miscarriage due to infection in pregnant women gonococcus
d. the grater in the cornea and permanent blindness due to infection in the eye gonococcus
e. of sepsis in newborns because of gonorrhea in women
f. advanced neurologic abnormalities due to meningitis gonococcal
g. destruction of the articular joint surface
h. destruction of heart valves
i. CHF or death from meningitis

PROGNOSIS
Prognosis in patients with gonorrhea depend quickly detected and treated disease. Patients may recover completely if done early and complete treatment. But if treatment is given too late, it's likely to cause further complications.

CONCLUSION
Gonorrhea is a bacterial infectious disease caused by bacteria N. gonorrhoeae. The disease is classified as Sexually Transmitted Diseases (STDs) because in most cases these infections occur through sexual contacts. In men generally causes temporary acute urethritis in women is usually asymptomatic. Diagnosis by elementary anamnesis, clinical examination, examination of smear preparation and examination of bacterial culture. Usually the group of patients treated with antibiotics and a good prognosis if therapy is quickly given.

Refferences

1. http://www.handsofhopegallup.com

2. http://www.irwanashari.com

3. http://www.soc.ucsb.ed

4. http://www.emedicinehealth.com

MENINGOCELE

DEFINITION

 Meningocele is considered less severe that myelomeningocele because the spinal cord doesn’t leave the protective bone tube. There is still a sack on the back, but the nerves of the spinal cord are not in it. The nerves remain protected and therefore are not as badly damaged. A person with Meningocele will usually have better physical development and bowel and bladder control.

What is Spina Bifida?
Spina bifida is a Latin term meaning 'open spine'. Medically it refers to a birth defect where the spine does not form completely . The spina bifida defect may leave several vertebrae deformed in such a way as to expose the spinal cord. The exposure of spinal cord usually results in some damage to it at the point of exposure. Damage at some point along the spinal cord results in limited brain signals to and from muscles and body organs below where the damage has occurred. Limited communication to and from the brain to
muscles and body organs frequently results in reduced development of normal body function. Although spina bifida is originally a skeletal defect, there are a significant number of directly related conditions which precipitate from the defect in the spine. People who are born with spina bifida frequently have one or more related defects.
The term meningocele may be used to refer to more than one condition. Spina bifida is a neural tube birth defect involving an abnormal opening in the spine. It occurs when the fetus's spine does not close properly during the first month of fetal development. In spina bifida occulta an opening in the spinal bones exists, but the neural tissue and membrane covering the spine (the meninges) are not exposed. Because there is no opening, the defect may appear as a dimple, or depression, at the base of the spine (the sacrum). Another sign of spina bifida occulta is the presence of tufts of hair at the sacrum. It is possible that while there is no opening, vertebrae are missing and there is damage to nerve tissue.
A meningocele is a sac protruding from the spinal column, which contains some of the spinal fluid and meninges. The sac may be covered with skin or with the meninges, and does not contain neural tissue. It may be located near the brain or along the spinal column. Hydrocephalus is rarely present, and the neurological examination may be normal. Because the neural tissue remains intact, it can be repaired by the experienced neurosurgeon, with excellent results.
A myelomeningocele is the most severe type of spina bifida because the spinal cord has herniated into the protruding sac. Neural tissue and nerves may be exposed. About 80% of myelomeningoceles occur at the lower back, where the lumbar and sacral regions join. Some people refer to myelomeningocele as spina bifida. Because of the exposed neural tissue, significant symptoms may be present. These symptoms may include:
•    muscle weakness or paralysis in the hips and lower limbs
•    no sensation in the part of the body below the defect
•    lack of bowel and bladder function
•    fluid build-up in the brain, known as hydrocephalus
Because of the risk of neural tissue damage, swelling, and infection into the spinal fluid and brain with an opening in the spinal column, surgery to repair the meningocele or myelomeningocele is usually done within 24 hours of birth. However, although the opening is closed, whatever damage has already been done to the neural tissue is permanent. If hydrocephalus is developing, the meningocele repair may be done first. Then, a few days later, a shunt can be inserted to resolve the hydrocephalus. If the hydrocephalus is present at birth, the two surgeries may be done at the same time to decrease the risks associated with increasing pressure on the brain. To prevent drying of the sac, it may be kept moist with sterile dressings until surgery is begun. Once the anesthesia has put the baby to sleep and the surgery is pain-free, a surgical incision is made into the sac. Excess fluid is drained, and the meninges is wrapped around the spine to protect it. The opening is then closed with sutures. 

DIAGNOSIS

If an individual has spina bifida occulta, with no outward signs of a neural tube defect and no symptoms, the condition may go undetected. The protruding sacs associated with meningocele and myelomeningocele are quite noticeable at birth. To understand the extent of the defect x rays, ultrasound, computed tomography (CT) scans, or magnetic resonance imaging (MRI) of the spine may be taken.
Spina bifida may be diagnosed while the mother is still pregnant, through prenatal screening. If spina bifida is indicated, a blood test will show an elevated alpha fetoprotein. However, elevated levels can be present without spina bifida, so further testing should be done if the test is positive. There is an elevated alpha fetoprotein level in about 85% of women with a fetus with spina bifida. An ultrasound can reliable reveal the spinal structure of the fetus. An amniocentesis may be done to check for chromosomal abnormalities. In amniocentesis, a long syringe is used to draw amniotic fluid out from the uterus through the mother's abdomen. Because the protruding sac of the meningocele and myelomeningocele can look the same on the outside, it is important to have a clear diagnosis, as the anticipated outcome of the two conditions is very different. 

TREATMENT

 Aftercare
The infant will first spend some time in the recovery room , and then be transferred to an intensive care unit . The infant will be monitored for signs of excess bleeding and infection. Temperature will be closely monitored. Antibiotics will be given to decrease the risk of infection, and the infant will be positioned to lie flat on the stomach to avoid pressure on the surgical wound. Extreme care is taken to keep the wound clean of urine and stool.

Risks
Surgical risks include infection and bleeding. Anesthesia risks include a reaction to the medications used, including difficulty breathing. During meningocele and myelomeningocele repair, there are additional risks of damage to the spinal column and infection of the spinal fluid surrounding the spine and brain. Damage to the neural tissue could result in paralysis, or loss of nerve function (for example, loss of bowel and bladder control). There may also be an increased risk of an urinary tract infection. An infection of the meninges is called meningitis. However, further damage would be expected if surgery were not done, and serious infection would be likely. As in all surgery, one must weigh the potential risks against the expected benefits.

Normal results
Results depend greatly on the extent of involvement of exposed neural tissue and the condition of the infant prior to surgery. A meningocele repair can have excellent results, as neural tissue does not extend into the protruding sac. In myelomeningocele, the amount of exposed neural tissue will determine the extent of lower limb weakness, or paralysis. The infant will usually spend a few weeks in the hospital after surgery before being able to be discharged home. As the child grows, it may be necessary to use braces, crutches, or a wheelchair for mobility. If surgery for hydrocephalus is successful, the prognosis is better. Children with a repaired myelomeningocele may be able to go to school, but will benefit from special education and associated services. There may be varying degrees of learning problems, and difficulties with the child's attention span. An effective bowel and bladder-training program can help make attending school easier. Because of muscle weakness or paralysis, a child with spina bifida will need physical therapy and may require future surgeries. 

Morbidity and mortality rates
With current medical and surgical treatments, about 85% of infants survive, and about 50% will be able to walk. Bowel and bladder disorders contribute significantly to morbidity and mortality in those with spina bifida who survive past the age of two years.

Alternatives
There is no alternative to surgical repair. Risk of infection and damage to the spine and brain is high with an opening to the spine, so surgery is necessary to close the opening and drain the excess fluid that could put pressure on the brain. The Spina Bifida Association of America recommends that all women of childbearing age take 0.4 mg of folic acid daily, as this amount has been shown to decrease the likelihood of neural tube defects. Once a woman is aware of being pregnant, the critical first month of neural tube development has already past, and folic acid cannot cure any damage that has been done.

Refferences

1. http://www.coloplast.com

2. http://www.ispub.com

3. http://www.projambi.co.cc

4. http://webeye.ophth.uiowa.edu

5. http://www.sbhac.ca

6. http://www.surgeryencyclopedia.com

MYELOFIBROSIS

DEFINITION

Mielofibrosis is a disease in the bone marrow in which collagen form a  fibrosis tissue in cavum marrow. This happens because the uncontrolled growth of blood cell precursors, which eventually led to the accumulation of connective tissue in the bone marrow. Connective tissue that forms blood cells which ultimately lead to dysfunctional form. Our bodies are aware of this, and tries to compensate by sending a signal to hematopoietic extramedulare organs, namely liver and spleen to produce new blood cells. But the blood cells that eventually produced by these organs is still not functioning properly and the body finally experiencing anemia. 

ETIOLOGY
Mielofibrosis idiopathic or primary mielofibrosis usually associated with genetic factors. The cause is idiopathic. There were no trigger factor, a epidemiologist who is expected to have some substance as causes, such as: Toluene, benzene, ionizing radiation. The highest incidence in patients due to radiographic contrast material administration with the basic ingredients of thorium, which is Torotras. Victims of the Hiroshima atomic bomb also has a 18 times greater risk than other populations, syndrome first appeared 6 years after exposure.

INCEDENCE

Mielofibrosis idiopathic about 2 from 1 million people. Approximately 10-15% of cases of idiopathic mielofibrosis appears at first as polistemia vera or essential thrombosis. MMM attack the middle and older age group, usually found at the age above 50 years, mean age 60 or 65 years, men and women have the same ability. MMM less frequently attack young age and rarely in children. 2 times boys than girls. In some reported cases of familial factors.

The occurrence of several conditions that Allows Mielofibrosis
A.    Neoplastic conditions
1.    Acute leukemia
2.    Chronic myelogenous leukemia
3.    Hairy cell leukemia
4.    Hodgkin's disease
5.    Lymphoma
6.    Multiple myeloma
7.    Myelodysplasia
8.    Metastatic carcinoma
9.    Polycythemia vera
10.    Systemic mastocytosis

B.    Non-neoplastic Conditions
1.    HIV infection
2.    Hyperparathyroidism
3.    Renal osteodystrophy
4.    SLE
5.    Tuberculosis
6.    Vitamin D deficiency
7.    Thorium dioxide exposure
8.    Gray platelet syndrome. 

PATHOGENESIS

Signs of mielofibrosis is an increase in staining reticuline. Fibrotic tissue was found on mielofibrosis tissue containing collagen and fibronectin, where reticuline staining (silver or Gomori) react with proteins contained in type III collagen and is usually estimated as a form of procollagen.
Idiopathic Mielofibrosis affects production of blood cells, erythrocytes very little is produced, too many leukocytes and platelets are produced.
Fibrosis in bone marrow may be able to describe the excess production of matrix. As already mentioned, this can be linked to many diseases. Matrix homeostasis resulting from the balance of formation and expenditure. Formation is influenced by growth factors, the most influential are the platelet derived growth factor (platelet-derived growth factor / PDGF), and expenditures described collagenase activity towards monocytes, macrophages and granulocytes. Therefore, diseases associated with mielofibrosis can be classified either according to the basic defect matrix production, decreased reabsorbs or both. If included in the category of both, can be characterized by deficiency of vitamin D because 1,25 (OH) 2D3 which is the active form of vitamin D3 inhibits megakarioycte and trigger the proliferation of monocyte differentiation / macrophages.

Some researchers believe that abnormal stroma of bone marrow is directly trigger the systemic circulation and dissemination of hematopoietic precursors by yet unknown mechanisms. This led to the hematopoietic ekstramedulare in the liver, spleen, limphonody or (usually) the kidneys, which causes metaplasie mieloid in these organs, which eventually become enlarged. Usually, hypersplenism also can contribute to the occurrence of cytopenia.
Among the adults whose mielofibrosis idiophatik, Cytogenetics of bone marrow analysis showed abnormal clone at roughly one-third of patients. By using comparative genomic hybridization technique, Al-Assar et al studied bone marrow mielofibrosis idiophatic and found chromosomal imbalances in 21 of 25 cases. Mutations of the gene 9p, 13q, 2q, 3p and 12q are common chromosomal abnormalities found. Hematopoietic origin of cell proliferation is more evenly with effected spleen and liver. There are secondary in the bone marrow fibrosis. Presumably precursor megakariocyt abnormal release of growth factors that stimulate fibroblasts.
The existence of mutagen is estimated as a factor that triggers produce clonal hemopatia on mielofibrosis. Cytogenetics abnormalities were not consistent as it changes its gene bcr / abl in CML, which was presented as a candidate gene important in pathogenesis. Changes in the molecular level of mielofibrosis remained unclear, until now still in the research.
Panel of candidate gene expression differences were observed between cytokine-independent progenitor cells from patients mielofibrosis with cytokine-progenitor progenitor (predicted normal). Immunophilin excessive FKBP51 expression in all patients studied and this function especially in cytokine-independence. Gata-1 transcription factor active on normal megakariocyte differentiation. In the rat study there were failures Gata-1 expression produces a syndrome resembling mielofibrosis. So the changes directly on the Gata-1 is important for the occurrence of mielofibrosis. Several genes associated with other growth have been investigated, for example: retino-blastoma gene that may have deletions or changes in calcitonin gene expression and methylation are experiencing. Mielofibrosis development may be related to abnormalities in the p53 gene or genes of race.
Mielofibrosis in MMM is a secondary reaction to the clonal hemopathy. Fibroblast cell secreting collagen that will be accumulated, these cells are normal and polyclonal. They are stimulated by cytokines released from megakariocyte and of clonal neoplastic cells developed hematopoitic other. Destruction and collagen synthesis occurs so that the concentration procollagen (results of collagen solution) is a marker of new collagen synthesis associated with disease activity. Collagen deposited in the extracellular space and vascular elements in the bone marrow. Four of the five types of collagen found here. Collagen type 1 and 3 is the main component of fibrosis in MMM, and increased collagen deposits equivalent to the duration of the disease.
At this early stage of MMM is the highest percentage of collagen type 3, whereas at the final stage of type 1 collagen (collagen polimetrik) the highest. In MMM there is a small portion of matrix molecules that contain more heksosamin than normal. Vascularization also increased, the extent of neovascularization is associated with the extent of disease and perhaps this is essential to the occurrence of fibrosis. Transforming growth factor (TGF) - β as the major mediator of collagen accumulation in the MMM. Cytokines are synthesized by endothelial cells such as megakariocyte and his case in the system monocytes - macrophages. TGF - β is more potent in secreting collagen than platelet derivate growth factor or epidermal growth factor and may regulate both these cytokines. TGF - β is also a potent stimulus to angiogenesis. 

The increase in TGF - β can be detected by increasing the circulation of platelets and which is a fragment megakariocyte MMM. Several other growth factors are also expected to stimulate fibroblasts in MMM, among others: Platelet derived growth factor contained in megakariocyte MMM, epidermal growth factor, endothelial cell growth factor, interleukin -1, basic fibroblast growth factor, and kalmoudulin. Several independent mechanisms to increase levels of cytokines in the bone marrow environment, among others: a simple secretion of granule - α megakariocyte, megakariocyte dysplastic bone marrow damage and destruction in the cytoplasm of megakariocyte by PMN leukocytes.

Distribution of hematopoietic ekstramedulare on MMM involving fetal liver and spleen. Model mielofibrosis by damaging blood vessels, the ultrastructure examination showed an increase beyond marrow hematopoietic which solidified, and began releasing hematopoietic precursors. Non ekstramedulare overgrown hematopoietic cell transfer. The liberation from marrow precursors similar to the damage results hematopoietic ekstramedulare sinusoids in cancer metastasis and may be a common mechanism.


CLINICAL FEATURES

In 25% of cases are asymptomatic looking mielofibrosis, diagnosis dissugestion in the presence of abnormal blood tests or splenomegaly inseidensil there. Clinical symptoms in general muscle fatigue and weight loss (7-39%), hipermetabolik syndrome (fever, night sweats present in 50-20% of patients), bleeding and bruised, sometimes there are times in the stomach, gout and renal colic, there are 4 - 6%, tophi are rarely obtained, diarrhea with no clear cause and pain Substernal sometimes found.
It can also be found pale in patients, palpitations, shortness of breath, itching, abdominal pain or discomfort in the abdomen, pain in the left shoulder or upper body left, spontaneous bleeding, bone pain , especially in the legs.

Clinical disorders for diagnosis of patients Mielofibrosis
Very frequently found (> 50% of cases)
• Splenomegaly
• hepatomegaly
• Fatigue
• Anemia
• leukocytosis
• thrombocytosis

Often found (10-50% of cases)
• Asymptomatic
• Weight loss
• Sweat night
• Bleeding
• Leukocytopenia
• Thrombocytopenia

Less common (<10% of cases)
• Peripheral edema
• Portal Hypertension
• Lymphadenopathy
• Yellow
• Gout


Substantial splenomegaly is a major physical discovery. Hepatomegaly was found in half of patients, 2-6% have portal hypertension, may be followed by complications: ascites, esophageal varices, gastrointestinal bleeding and hepatic encephalopathy. Also found petechiae, ekhimosis, and limfadenopatia. Some patients show a similar dermatosis neutrofilik sweet-syndrome and suffered hematopoietic ekstramedulare dermal, who partially followed osteosclerosis periostitis with bone pain and deafness. When the surface of the serous was involved in hematopoietic may have pleural effusion or ascites and perikard. Sometimes followed by neurological complications such as: elevation of intracranial pressure, delirium, coma, subdural hemorrhage, damage to motor, sensory and paralysis.
The following grouping of symptoms according to the cause
• hepatosplenomegaly:
o Enlarged abdomen
o Abdominal pain
o Weight loss
• Symptoms of Anemia:
o Fatigue \
o Shortness of breath
o Weakness
o Looks pale
o Palpitations
• Symptoms of Infection:
o Fever reach or over 38 ° C
o Chills
o Sweat night
o Coughing
o Sore throat
o Blisters on the lips or mouth
o The heat or pain during urination
o Swelling that does not get better, remove secretions, redness and warm to the touch
o Stiff neck
• Symptoms of Bleeding:
o Easy bleeding
o Bleeding massive and elongated
o spontaneous bleeding
o severe head pain or impaired vision
o Stiff neck
o Joint pain
o Petechiae

Examination Support
a. Blood
On examination of peripheral blood cells obtained tear drop-shaped erythrocytes which are connected the core in circulating erythrocytes, leukocytes and neutrophils immatur abnormally large platelets. Reticulocyte increases; erythrocyte policromasia, fragmentation and target cells are also frequently found. These morphological abnormalities caused by changes hematopoietic, free cell earlier than bone marrow and hematopoietic ekstramedulare. How did these changes occur remains unclear.
Anemia with hemoglobin less than 10 g / dl were found in 60% of cases, which can occur due to hemodilution from increased plasma volume, impaired bone marrow production and hemolysis. Patient's peripheral blood smear mielofibrosis: aniso-poikilositosis, oval of erythrocyte, leukomoid reaction (granulocytes side there is one metamielosit, one promielosit and one normoblast). While the cause of hemolysis is estimated: hypersplenism, autoantibodies erythrocytes, hemoglobin H are obtained and the sensitivity of the complement membrane similar PNH (Paroxysmal nocturnal hemoglobinuria).
The morphology of anemia is not generally normositik normokromik KHS, makrositik if folic acid deficiency and microcytic hipokromik when Fe deficiency or gastrointestinal bleeding. The number of leukocytes increased at 50% of cases, followed by eosinophilia and basofilia, while the number of normal lymphocytes. Some meiloblas found in the peripheral circulation and may not have considered the conversion towards acute leukemia, but mieloblas concentration> 1% memeberikan poor prognosis. Also found hipersegmen neutrophils, increases neutrophil enzymes, platelets increased in early MMM, on the progression of the disease can occur thrombocytopenia.
Platelets are usually large, in the circulation megakariocyte found intact or undergo fragmentation. Often abnormal platelet function, bleeding time disruption and retraction jendalan and decline: levels of platelet factor 3, platelet adhesiveness and lipogenesis activity. Changes in soluble factor that can terajdi pemebekuan the disease. Disseminated intravascular coagulation (DIC) subclinical can be found in 15% of MMM patients with advanced form and acquired factor V deficiency can occur in patients tersebnut above. Uric acid levels and lactate dehydrogenase enzyme is almost always increased, describing the existence of an excessive period of hematopoietic cells or the hematopoietic an ineffective or both. It can also increase serum levels of enzymes alkalinefosfatase which is bone involvement, a decline in levels of albumin, cholesterol and lipoproteins. Can increase levels of vitamin B12 in patients with leukocytosis, which is a reflection of the increase in the neutrophil.

b. Bone marrow
Aspiration of bone marrow may not be successful (drytap) and requires a bone marrow biopsy to diagnose MMM. A consensus has been made by the Italian Society of Hematology.
Morphology and clinical data were combined to diagnose appeal MMM from other CMPD disease, and from mielodisplasi syndrome with bone marrow fibrosis. The criteria were: bone marrow fibrosis and bone marrow hyperplasia morphology disorder and hematopoietic ekstramedulare. The three elements above must be contained to the criteria MMM.
Fibrosis have occurred in all cases of MMM, and usually in the patient information. In the early stages of fibrosis were minimal and bone marrow hyperplasia may be more clear. The above situation is called cellular phase MMM. When bone marrow fibrosis patients suspected not proven MMM, have taken material from other places, because the spread is uneven.
Fibrosis may need to be graded by a system that has been publicated and proven. When the massive fibrosis, cellularity whole will go down, but there remain megakariocyte hyperplasia. Bone marrow sinusoids will be widespread, there has been hematopoietic intravascular.
The increase in the number of mast cells can be observed in patients with a fibrosis at the time of biopsy. In the preparation of bone marrow smears, not a cursory look kelaianan, but often found hyperplasia neutrofilik and megakariocyte. The presence mikromegakariocyte and makromegakariocyte can be found, giving rise to nuclear-cytoplasmic asynchrony.
Granulocytes can be hypo or hiperlobulasi so memeperlihatkan Pelger-Huet anomaly obtained or the presence of nuclear-cytoplasmic asynchrony. Precursor erythroid normal or increased, which can be checked by scanning isotope sulfur colloid bone marrow for cell retikuloendoteliel and with colloidal iron for cell erythroid indicating an expansion in the bone marrow to the long bones of normal inactive.

c. Chromosome abnormalities
Half of MMM patients contained clonal karyotype abnormality. Only a few patients showed abnormalities in metaphase, which proves the MMM patients hematopoietic leaving normal cells. Often found deletion of chromosome segments linked to the retinoblastoma gene, del 13 (q13q21) and del 20q. Chromosomes are often disrupted are: 1,5,7,8,9,13,20 and 21. Form of trisomy and monosomy, partial deletions and translocations are also frequently found. Fibroblasts do not contribute to chromosomal abnormalities in MMM.

d. Damage to the immune system
Clinically immune system abnormality common in MMM, this contrasts with other CMPD. T and B lymphocyte cells directly affected by stem cell defect in MMM and functional defects of B cells and T may be shown. Variations humoral immune system abnormalities have been found. The reduced levels of C3 may occur and cause a rise in the possibility of bacterial infection. Pathological autoantibodies may be found among others: Erythrocyte autoantibodies, platelet antibodies, antinuclear antibody, antiimunoglobulin and antibody antiphosfolipid. In MMM filtered lymphoid bone marrow. Monoclonal Gamopati to arise 10% of MMM patients, in some cases the simultaneous occurrence of MMM and plasma cell dyscrasias have been reported.

d. Pathological examination
Typical picture of the MMM is the presence of bone marrow fibrosis and hematopoietic ekstramedulare. Bone marrow fibrosis followed the osteosclerosis 30-70% of cases, especially regarding the axial skeleton and the proximal long bones. Cortical bone is thickened and the normal pattern of trabeculae disappeared. Hematopoietic mainly occurs in the spleen in the presence of splenomegaly, liver and some other organs can also be involved, for example: lymph node, kidney, adrenal, periosteum, intestines, pleura, lung, fat tissue, skin, mammary, dura, ovarian and thimus. Hematopoietic cluster may contain a mixture of derivatives and possible precursor mieloid seen as microscopic or tumor infiltrates makroskopis. The proportion of erythroid ekstramedulare higher on the side rather than in bone marrow and hematopoietic ekstramedulare, there is a tendency of low mitotic index, immature cells and megaloblastic higher than hematopoietic medulare . Damage target organ may occur due to physical pressure around normal tissue, but normal architecture can still be maintained.


Italian Consensus Conference for the Diagnosis Mielofibrosis
A.    Major Criteria
1.    Diffuse bone marrow fibrosis
2.    The loss of T9: 22 chromosome or bcr / abl Rearrangement in peripheral blood cells
3.    Splenomegaly
B.    Minor Criteria
1.    Anisopoikilocytosis with tear drop red cells

3.    Clustred marrow megakaryoblast and anomalous megakariocytes
4.    Metaplasia mieloid


Management
The goal of treatment is to reduce symptoms and reduce the risk of complications. MMM may be cured with hematopoetic stem cells Transplantation (HSCT), but usually successful HSCT for younger patients and represents a significant risk of death. No other form of therapy to prolong survival or prevent the progression mielofibrosis.
Supportive therapy is directed directly to the complications that occur. Some patients are asymptomatic and require observation. Allopurinol is given to maintain blood uric acid levels remain normal, to inhibit: nefropathy vein, renal calculi and gout. Anemia and thrombocytopenia may arise, and will continue until symptoms develop. When some failed to improve hematopoietic therapy, transfusion is required to maintain blood count. Folic acid supplementation is necessary because of frequent occurrence of hemolysis. Blood transfusions can be given to overcome the anemia that occurs in patients.

a. Antirachitis
Mielofibrosis has been described that can occur in patients and lead to deficiency of vitamin D. In addition, patients mielofibrosis associated with trombositemia esencial or mielomonositik leukemia, as acute (idiopathik) mielofibrosis, has given good response to vitamin D. Vitamin D and its analogues can suppress proliferation and repair mielofibrosis megakariocyte associated with rickets. Direct inhibitory effects on thrombosis has been demonstrated. However, some studies do not show the same response on paien with idiopathic mielofibrosis.
Commonly used are calcitriol, which is the primary active metabolite of vitamin D3. it can increase calcium levels by triggering the absorption of calcium from the digestive tract and in urine retention. The dose given to patients mielofibrosis higher than 5 to 10 times the physiological dose. In adults is usually 2.5 mcg / day, orally. Contraindications hypersensitive patients, hypercalcaemia or the presence of malabsorption syndrome.

b. Corticosteroid
These drugs have immunosuppressive and cytotoxic effects. Cytotoxic mechanism of corticosteroids is still not yet known (but apparently through the glucocorticoid receptor). Preparations are usually used is prednisone which act as immunosuppressants in autoimmune disorders. Prednisone can reduce the effects of inflammation by increasing capillary permeabilizas and suppressing PMN activity. Prednisone also can mensstabilkan lysosome membrane and also suppress the production of lymphocytes and antibodies. Efficiency in some cases may reflect an underlying autoimmune defect and / or pressing clones proliferated.
The usual dose is 50-60 mg / day orally. Contraindicated in patients with hypersensitivity, viral infection, peptic ulcers, insufiensi liver, connective tissue infections, fungal infections or tuberculosis of the skin, gastrointestinal bleeding or ulceration of the gastrointestinal tract.
Moreover, it can also be used methylprednison which can suppress the inflammatory process by pressing the spread of PMN leukocytes and also increase capillary permeability.

c. Immunomodulator
Immunomodulator can suppress the autoimmune process, triggered imunoregulasi of abnormal clones. Preparations commonly used are interferon alpha 2a. treatment with these preparations has shown efficient results in the long term for adult patients. Interferon considered because it can suppress the activity of TGF - β and its effectiveness in CML. Interferon - α might be beneficial relieve bone pain, thrombocytopenia and splenectomy, but the effectiveness is decreased by a flulike syndrome and memberatnya severe anemia. The dose commonly used 1-6 million units / day, subcutaneous. It can also be used thalidomide preparations. Thalidomide is statu immunomodulatory agent that can suppress excessive production of tumor necrosis factor alpha (TNF-α) and can decrease adhesion regulation of cell membrane associated with the migration of leukocytes. Because some peretimbangan, including teratogeniknya effects, thalidomide is not freely sold and only given by doctors who are responsible for their patients and only sold by pharmacies who have been enrolled in the program and Safety Education Thalidomide Perscribe (STEPS). Patients must follow a survey that will be executed while getting therapy, and thalidomid only be granted for a period of 28 days.
These preparations are widely used to improve anemia and reduce transfusion of blood or thrombosis associated with mielofibrosis. Patients with severe MMM antiangiogenic preparations can be given thalidomide, 20% of cases occur constitutional symptoms improved with the decrease, the size of the spleen and improvement of blood counts. Serious side effects reported include: severe leukocytosis and thrombocytosis hematopoietic ekstramedulare pericardial, and can occur at very low initial dose of 50 mg / day.
Some researchers provide a combination of thalidomide 50 mg / day with prednisone 0.5 mg / kg / day, 95% complete response within 3 months of treatment. A single dose of 200 mg / day, per oral, then dose titration to achieve the target dose of 800 mg / day, orally. In combination with the provision of prednisone, used 50mg/hari per oral dose.

d. Allogenic hematopoietic stem cell Transplantion
Almost all patients with CMPD may be cured with Allogenic hematopoietic stem cell Transplantation (AHSCT). Limitation of this approach because the factor of age and condition of the patient, using a suitable donor match and morbidity and mortality associated with the procedure. The presence of bone marrow fibrosis and splenomegaly apparently not a barrier to HSCT.
Reported by Guardiola et al (1999) and Jurado et al (2001) Internacional cooperative group trial with 55 patients, almost all young age, mean age 42 years, with HLA-identical related donor. MMM with age> 45 years 5-year survival by 14%. The more it becomes clear, that in younger patients with 2 risk factors, with a predicted low survival, with no curative treatment, HSCT performed immediately considered the diagnosis Estela upright. For older patients with HSCT may provide a low-end result and a bad risk factor is not found, then you should first reach difunda risk factors emerged, although data on this subject has not been widely reported.

e. Androgens and Corticosteroid Therapy
The hormone androgen can be administered in anemia due to MMM. With a response rate of 29-57%. Munngkin spontaneous improvement can occur in MMM, so that the response to therapy should be carefully analyzed. Women with minimal splenomegaly and patients with normal karyotype provide better prognosis. Before therapy with androgens, men need prostate gland screened both physically and with prostate-specific antigen, in women to consider the effects of virilization. During androgen therapy should be monitored with liver function.
Some dosage schedules have given quite good results, including an oral synthetic androgen: fluoksimesteron, dose: 2 - 3 times 10 mg daily. If no improvement Estela 3-6 months of therapy, the androgen should be discontinued. Some patients who do not respond to androgens, the possibility of a response other preparations, due to shortened erythrocyte survival in MMM, the possibility of adrenal corticosteroids improve the vitality of erythrocytes and fix anemia. Oral prednisone, with the dose: 1 mg / kg per day, giving a response in 25-50% of patients. The best responses have been reported in female patients. Patients with hemolysis should be given folic acid supplements. Androgens and corticosteroids can sometimes be combined. Dose started with prednisone 30 mg / day, with a combination fluoksimesteron 10 mg twice a day, if there is a response after one month of therapy, reduced dose prednisone tappering off while fluoksimeteron resumed.
f. Chemotherapy
Chemotherapy rarely give haematological remission, and does not provide general changes in MMM, but may be very dramatic change in symptoms. Chemotherapy can reduce the hepatomegaly and splenomegaly and improve weight loss, fever and night sweats to 70% of patients, and reduce leukocytosis, thrombocytosis, and anemia. Chemotherapy has also been used: busulfan, melfalan, 6-tioguanin and hydroxyurea. In MMM chemotherapy should be more careful because there tends to be toxic to bone marrow than other CMPD. For example, busulfan administration 2-4 mg / day had a maximum dose that can be provided with a degree of safety in the MMM. Patients should be monitored by frequent and continuous, especially when emerging cytopenia.
Hydroxyurea can be given reduced doses of 500-1000 mg daily intervals, with dose adjustments depending on clinical response and blood counts. Hydroxyurea (Hydrea) has effect:
• Lowering the platelet counts are too high
• Reduce the size of splenomegaly and complications
• Reduce or eliminate night sweats and weight loss
• Increasing the hemoglobin concentration
• Sometimes it can reduce the degree of bone marrow fibrosis

g. Irradiation
Patients with hypersplenism may be able to respond with irradiation splenik, especially bial there is a contraindication to splenectomy. Almost all patients had improvement of pain complaints and> 50% reduction in spleen size. Irradiation splenik will provide improvements cytopenia, given by a small faction with close monitoring. Dose fractions of 15-100 cGy, 2 -3 times per week. Total dose of 700 - 2400 cGy to provide results that comfortable with the tolerance of toxicity. Preliminary results can only be seen after several months. Tumor hematopoietic ekstramedulare also symptomatic response to irradiation therapy, especially suitable in bone pain from a tumor or on deposit periostitis and central nervous system.

h. Splenectomy
Splenectomy be considered in patients refractory to therapy: cytopenia, portal hypertension, or symptoms due to hypersplenism. With splenectomy deliver improved: symptoms hypersplenism, portal hypertension, anemia and thrombocytopenia, although these improvements are not always able to be maintained after one year of action. Splenectomy in MMM must be careful, because organomegaly large enough so that it may happen adhesions, increase blood flow and compromised status of patients. The existence of DIC (KID) light which marked an increase of D-dimer levels are often found in MMM, with the risk of bleeding that is not easily corrected preoperative. Acute surgery mortality can reach 38%, at an early stage of disease, whereas mortality in hospital care that is more modern down <10% and 25% within 3 months. Splenectomy sometimes cause Aplastic crisis as a place hematopoietic ekstramedulare lien on severe bone marrow fibrosis. Splenectomy reported any significant complications: intraabdominal infection, severe thrombocytosis and hepatomegaly with rapid thrombosis enlarged. Last two cycles of chemotherapy may require pascaoperatif.
Splenectomy be considered for patients with: a. Transfusion needs that can not be accepted; b. Massive splenomegaly causes unpleasant symptoms that can not be controlled by radiotherapy or chemotherapy and c. Severe thrombocytopenia accompanied by recurrent bleeding.
In advanced disease with severe splenomegaly, the risk is very big surgery, patients in poor general condition and high death rates due to post operative bleeding and infection. Post-splenectomy thrombocytosis has a high risk of thromboembolism.

i. Other Treatment
Anagrelid can lower platelets but does not improve other clinical abnormalities. Some patients may be given eritropoetin even better when combined with interferon. Suramin and imatinib reportedly been given to the MMM, with unclear results.
Mechanical curettage of the iliac bone marrow fibrotic tissue, is expected to increase fixing hematopoietic and anemia, although this complex procedure and not always successful in all patients.
Analog HSCT after high-dose busulfan, ever done on a number of advanced MMM is refractory to other therapies, although with relatively high mortality (6 of 12 patients), almost all patients with symptoms of hypersplenism and improvement occurred half of patients been improved anemia and thrombocytopenia.
         
Diagnosis
Diagnosis is based on the triad MMM: bone marrow fibrosis, hematopoietic ekstramedulare and hematopoietic clonal with no discovery of the underlying disease. Found no sign - a sign of clonal hematopoietic pathognomonic and evidence are not directly when not found an abnormal karyotype. Bone marrow biopsy is necessary to determine the presence of fibrosis and prove the existence of clonal hematopoietic in the form panhiperplasia and to get rid of the infiltration process. For diagnosis using concensus Italian conference even though they may not apply to the early phase of MMM.
MMM need to be distinguished from CML, ET and PV. When bone marrow fibrosis as the main picture then the diagnosis becomes difficult. PV ended with MMM like syndrome is 15-20%. Mielofibrosis in PV is more common after several years of travel sickness. Because patients with PV postpolisitemik, become symptomatic due to the expansion of the red blood cells and into the early attention, and its diagnosis is usually made prior to bone marrow fibrosis arise. Patients with PV, first discovered the existence of phase mielofibrosis postpolisitemik more progressive way than the MMM Patients. Mielofibrosis can also occur in CML, but with a MMM deferensial diagnosis based on genetic analysis.
Mielofibrosis also can be caused by a reaction to: malignancy, infection and some other. It can be connected with change of hematopoietic peripheral blood and looking like MMM.
Mielofibrosis secondary diagnosis based on the underlying disease. Secondary Mielofibrosis a regular description of certain conditions including postpolisitemik PV and a rare complication of systemic lupus erithematosus and rickets. When mielofibrosis because infection is usually chronic form, spread widely and is usually easy to detect. Almost all secondary mielofibrosis due process of malignancy. Examination of urine hidroksiprolin a metabolite of collagen can distinguish between secondary mielofibrosis with MMM. In MMM normal excretion, in the process of malignancy and secondary mielofibrosis excretion increases.
Treatment of secondary mielofibrosis especially treatment of the underlying primary disease. Improved treatment of fibrosis, is reported after successful treatment of PV, Hodgkin's disease, metastasis of prostate and mammary carcinoma.

2.8 Prevention
In addition to the above treatment can be given, there are also several steps can be taken of patients who can mnegurangi mielofibrosis or prevent the occurrence of symptoms, namely:
• Avoid exposure of people or a crowd that brought flux or other infectious diseases if the patient leukocyte levels low.
• Making good hygiene, including washing hands in frequency.
• Brushing your teeth regularly, clean themselves (bath) regularly and notice the areas that are hard to clean like the folds of skin around the rectal area.
• Avoid activities that can cause bruising.
• Use an electric shaver, and be careful when cutting the nails, use a knife, etc..
• Use shoes with hard soles, gloves and long pants while doing outdoor activities such as gardening.
• Use a soft toothbrush if you have had bleeding gums.
• Avoid the use of aspirin or other medications that are similar to aspirin (eg Motrin, Ibuprofenther medications that are similar to aspirin (eg Motrin, Ibuprofen, anti-inflammatory or other) unless it is absolutely necessary. These medications can affect blood clotting.
• A balanced diet, because it can help the body produce new red blood cells.
• Sleep and rest enough to save energy.
• Come with a mild exercise, like brisk walking, which is intended to stimulate circulation and increase energy levels.
• Tell the dentist's other patients and medical staff who may be involved with the patient that the patient had the disease, because there is a high bleeding risk from infection and bleeding while undergoing multiple procedures.

Prognosis
As leukemia, mielofibrosis develop progressive and often requires therapy to control disease. Mielofibrosis can develop into acute lymphocytic leukemia or lymphoma. Although a number of factors to predict survival time has been spent, but usually the survival rate or developments anemia usually have poor prognosis. Survival rate in patients mielofibrosis usually 5 years.
On average MMM can survive 3-7 years and approximately 20% over 10 years to life. Median life extension - about 3-4 years but many patients live 10 years or more. Less than 10% of patients experienced late transformáis become acute leukemia. Prognosis was estimated according to the mid-emergence time blast crisis in CML and possibly worse in ET and PV. Patients with evidence of more disease provide more short survival. Jira better prognosis: there are no constitutional symptoms, Hb> 10gr/dl, platelets> 100 x 10 9 / L and no hepatomegaly. Younger patients have better survival skills, like its low concentration in the circulation mieloblas. Cytogenetics abnormalities including single clone with a translocation of chromosome 1, 5q-, Trisomy 8, 13q-, or 20q-, perhaps with a worse prognosis than a normal karyotype. Similarly, patients with increased plasma volume or increased levels of soluble IL-2 receptor and have poorer survival. 3
Reily, Snowden and Spearing et al (1997) makes several score prognosis include: age, Hb level, symptoms of the constitution and karyotype. Mayo can also be used Prognostic Scoring System (MPSS), which includes:
• Hemoglobin greater than 10 mg / dl
• Calculate the leukocytes of less than 4 or more than 30 x 109 / L.
• Platelet count less than 100 x 109 / L
• Calculate the absolute monocyte type equal to or greater than 1 x 109 / L. 2

Patients were categorized according to risk group with the shortest survival of 16 months and the longest 180 months. As time goes by symptoms and become heavy despite cytopenia be happening spontaneously repair. Some of the problems that arise such as: weight loss, edema extremitas down, infections especially pneumonia. Almost all patients with splenomegaly occurs increasingly become heavy, causing pain and bone pain.
Most patients with portal hypertension with esophageal varices, a result of: increased blood flow splenoportal, hepatica vein thrombosis, portal vein thrombosis, post-transfusion and hematopoietic haemochromatosis intrasinusoid.
Bleeding can be caused by thrombocytopenia, platelet defect, disseminated intravascular coagulation (DIC) or deficiency of factor pemebekuan. MMM patient deaths caused by variated among others: infection, bleeding, heart failure, cerebrovascular accidents, renal failure, liver failure and thrombosis. Conversion towards leukemia reported 50-20% of cases. This shift toward leukemia not clear, some cases without exposure sitostatica therapy, the incidence of acute lymphocytic leukemia direction similar to acute Mieloid Leukemia