Sandbox:Hamid
Hamid Qazi, MD, BSc 
Salm..
==Historical Perspective== 

## Discovery
- Salmonella was first discovered by Daniel E. Salmon, an American veterinarian, who first isolated Salmonella choleraesuis from pigs in 1884 with hog cholera.
- The association between  and  was made in/during .
- In ,  was the first to discover the association between  and the development of .
- In ,  mutations were first implicated in the pathogenesis of .

# Outbreaks
- There have been several outbreaks of , which are summarized below:

# Landmark Events in the Development of Treatment Strategies
- In ,  was developed by  to treat/diagnose .

# Impact on Cultural History

# Famous Cases
- The following are a few famous cases of disease name:

# Classification
-  may be classified according to Kaufmann-White typing system into  subtypes:
Somatic O
Surface Vi
Flagellar H antigens
- Somatic O
- Surface Vi
- Flagellar H antigens

# Pathophysiology
After ingestion, infection with salmonellae is characterized by attachment of the bacteria by fimbriae or pili to cells lining the intestinal lumen. Salmonellae selectively attach to specialized epithelial cells (M cells) of the Peyer patches. The bacteria are then internalized by receptor-mediated endocytosis and transported within phagosomes to the lamina propria, where they are released. Once there, salmonellae induce an influx of macrophages (typhoidal strains) or neutrophils (nontyphoidal strains).
The Vi antigen of S typhi is important in preventing antibody-mediated opsonization and complement-mediated lysis. Through the induction of cytokine release and via mononuclear cell migration, S typhi organisms spread through the reticuloendothelial system, mainly to the liver, spleen, and bone marrow. Within 14 days, the bacteria appear in the bloodstream, facilitating secondary metastatic foci (eg, splenic abscess, endocarditis). In some patients, gallbladder infection leads to long-term carriage of S typhi or S paratyphi in bile and secretion to the stool.  As a rule, infection with nontyphoidal salmonellae generally precipitates a localized response, while S typhi and other especially virulent strains invade deeper tissues via lymphatics and capillaries and elicit a major immune response.

## Pathogenesis
- It is understood that  is the result of / is mediated by / is produced by / is caused by either , , or .
-  is usually transmitted via the  route to the human host.
- Following ingestion, salmonella uses the  to invade the  cell.
-  arises from s, which are  cells that are normally involved in .
- The progression to  usually involves the .
- The pathophysiology of  depends on the histological subtype.

# Genetics
-  is transmitted in  pattern.
- Genes involved in the pathogenesis of  include , , and .
- The development of  is the result of multiple genetic mutations.

# Associated Conditions

# Gross Pathology
- On gross pathology, , , and  are characteristic findings of .

# Microscopic Pathology
- On microscopic histopathological analysis, , , and  are characteristic findings of .

# Overview

# Historical Perspective
===Discovery===
- Peutz-Jeghers syndrome was first discovered by Dr. Connor, a British, in 1895 in identical twin sisters.
- The association between gastrointestinal polyposis with distinctive pigmentation of the skin and Peutz-Jeghers syndrome was made in 1921 by Dr. Johannes Peutz of Holland.
- In 1949, Dr. Harold Jeghers of United States was the first to discover the association between combination of intestinal polyposis and skin pigmentation, and the development of Peutz-Jeghers syndrome.
- In 1954, A. Bruwer used the eponym Peutz-Jeghers syndrome
- In 1998, serine/threonine-protein kinase 11 alias LKB1 (STK11/LKB1) gene mutations were first implicated in the pathogenesis of Peutz-Jeghers syndrome.

# Classification
- There is no established system for the classification of Peutz-Jeghers syndrome.

# Pathophysiology

## Pathogenesis
- It is thought that Peutz-Jeghers syndrome is the result of deletion or partial deletion of STK11 (LBK1) gene, located on chromosome 19p13.3.
- STK11 protein plays an important role in second messenger signal transduction and is found to regulate cellular proliferation, controls cell polarity, and responds to low energy states.
- In Mammalian studies, STK11 is shown in the inhibition of AMP-activated protein kinase (AMPK), and signals downstream to inhibit the mammalian target of rapamycin (mTOR).
The mTOR pathway is dysregulated in Peutz-Jeghers syndrome.
- The mTOR pathway is dysregulated in Peutz-Jeghers syndrome.

## Pathology
- Peutz-Jeghers syndrome associated polyps have a unique smooth muscle core that arborizes throughout the polyp.
These polyps can only be differentiated from other polyp types by histopathology.
- These polyps can only be differentiated from other polyp types by histopathology.

## Causes
- Peutz-Jeghers syndrome is caused by STK11 gene mutation
- Variable penetrance

# Epidemiology and Demographics

## Prevalence
- The prevalence of Peutz-Jeghers syndrome is estimated to be 1 in 8300 to 250000
- Most likely prevalence is 1 in 100000

## Age
- Peutz-Jeghers syndrome affects individuals between the ages of 10 to 30 years; average age of diagnosis is 23 years for males and 26 years for females.

## Gender
- Males and females are equally affected.

# Risk Factors
- There are no established risk factors for Peutz-Jeghers

# Screening
- According to the American College of Gastroenterology (ACG) and the National Comprehensive Cancer Network (NCCN), screening for Peutz-Jeghers syndrome by physical exam, complete blood work for iron deficiency anemia, and endoscopy are recommended every year among patients with Peutz-Jeghers Syndrome.

# Natural History, Complications, and Prognosis

## Natural History
- The symptoms of Peutz-Jeghers syndrome usually develop in the first decade of life, and start with symptoms such as hyperpigmentation, abdominal pain, and rectal bleeding.
- If left untreated, patients with Peutz-Jeghers syndrome may progress to develop colon cancer, breast cancer, and gastrointestinal cancers.
- Extraintestinal manifestation include pancreatic, lung, breast, uterine, ovarian and testicular malignancies.

## Complications
- Common complications of Peutz-Jeghers syndrome include:
Intussusception
Gastric outlet obstruction
Extraintestinal polyps
- Intussusception
- Gastric outlet obstruction
- Extraintestinal polyps

## Prognosis
- Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with  is approximately %.
- Depending on the extent of the  at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as poor/good/excellent.
- The presence of  is associated with a particularly  prognosis among patients with .
-  is associated with the most favorable prognosis.
- The prognosis varies with the  of tumor;  have the most favorable prognosis.

## Signs and Symptoms Differential compared to Peutz-Jeghers Syndrome
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## Use if the above table can not be made

# Differentiating Gastrointestinal Bleeding from other Diseases