2 diego vergani rejection& tolerance in lt

•

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Osama Arafa

international pediatrics conference of gastroenterology & nutrition Hurghada 2013

Health & Medicine Technology

Diego Vergani - Institute of Liver Studies
King’s College London School of Medicine
at King’s College Hospital, London UK
Rejection and tolerance
in liver transplantation

Cellular liver rejection
 Common
 Due to T-cell recogniton
of alloantigens

Cellular immunity physiology
 T-cell activation
 T-cell commitment

Th
naive
APC
IFN-
IL-4
Costimuli 1986, Mosmann &
Coffman
Th0
Th2Th1
Cell mediated
Immunity
Humoral
Immunity
IL-12
IL-4, IL-10
ModifiedfromNickersonetal

Th
naive
APC
Costimuli
ModifiedfromNickersonetal

Th
naive
APC
Costimuli
Th0
ModifiedfromNickersonetal

Th
naive
APC
Costimuli
Th0
Th1
Cell mediated
Immunity
IL-12
ModifiedfromNickersonetal
Rejection

Th
naive
APC
IL-4, IL-10
Costimuli
Th0
Th2
Humoral
Immunity
ModifiedfromNickersonetal
Tolerance

Th
naive
APC
Costimuli 1986, Mosmann &
Coffman
Th0
Th1
IL-12
ModifiedfromNickersonetal
Rejection
Th2
Tolerance
IL-4, IL-10
IFN-

Th
naive
APC
Costimuli 1986, Mosmann &
Coffman
Th0
Th2
IL-4, IL-10
ModifiedfromNickersonetal
Tolerance
Th1
IL-12
Rejection
IL-4, IL-10

Immune mechanisms of
 Rejection
 Tolerance

Th1
APC
IL-2
IL-2R
Costimuli
Allograft
Rejection
Alloantigen
Modified from Nickerson et al

Th1
CTL
APC
IL-2
Costimuli
Allograft
Rejection
Alloantigen
Modified from Nickerson et al

Th1
CTL
APC
IL-2RIL-2
IL-2R
Costimuli
Allograft
Granzyme B
Rejection
Alloantigen
Modified from Nickerson et al

Th1
IFN- IFN-
CTL
APC
DTH
Costimuli
Allograft
Rejection
Alloantigen
IL-2
IL-2R
IL-2R
Modified from Nickerson et al

Th2
pCTL
APC
IL-4R
IL-2R
Allograft
Tolerance
Alloantigen
Modified from Nickerson et al

Th2
pCTL
APC
IL-4R
IL-2R
Allograft
Tolerance
Alloantigen
IL-4
Modified from Nickerson et al

Th2
pCTL
APC
IL-4R
IL-2R
Allograft
Tolerance
Alloantigen
IL-10
IL-4
Modified from Nickerson et al

Th2
pCTL
APC
IL-4
IL-4R IL-2R
Allograft
Tolerance
Alloantigen
Th1
IL-10
IL-10
Modified from Nickerson et al

PATIENTS
72 paediatric liver transplant recipients
with normal liver function for > 6 months
29 healthy children
(15 M, median age 2 yrs, 2 days - 13 yrs)
CONTROLS

‘Tolerant’
Median CyA trough level 70ng/ml [range: 0-80]:
13 patients [6 M, median age at transplant 4 yrs
(range: 8 mths – 10 yrs.)]
‘Non-Tolerant’
CyA 150ng/ml (90-250), or Tacrolimus 7mg/l (5-12):
59 patients [32 M, median age at transplant 3 yrs
(range: 6 mths - 10 yrs)]
PATIENTS

100
60
20
0
Normal ‘Tolerant’ ‘Non -tolerant’
TGF-b1(pg/ml) Levels of TGF-b1
N S

‘Non-Tolerant’‘Tolerant’Normal
500
0
1000
IL-4(pg/ml)
N S
Levels of IL-4

‘Tolerant’Normal
0
500
900
IFN-(pg/ml)
Levels of IFN-
P=0.003
‘Non-
Tolerant’

IL-10(pg/ml)
‘Tolerant’ ‘Non-
Tolerant’
2000
Normal
0
4000
P= 0.005
6680
6995
7650
7490
9297
9280
Levels of IL-10
9303

IL-10/IFN-Ratio IL-10/IFN- ratio
‘Tolerant’
1000
3000
5000
‘Non-Tolerant’
P= 0.00001

T cell activation
Possible sites of
intervention

Tacrolimus
Calcineurin
inhibitors
Ciclosporin

Knowledge of rejection mechanisms is
key to:
Designing rationale regimens
Developing new modes of intervention

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A previously healthy 3-year-old female presented to our pediatric clinic with two days history of high temperature 38- 40 c Mother gave ibuprofen susp. With diclofenat in alternative way aiming to control temperature . On the second day the mother asking to medical advice for this illness and she was diagnosis as acute tonsillephyrgitis and azithoromcin described to ttt the infection At that time only the increase in temperature & mild abdominal pain there is no vomiting or diarrhea At night the mother called here doctor prescribing a bloody stool twice with no vomiting or colic He ask the mother to do abdominal ultra sound & erect X RAY for her daughter But the results was –ve nothing wa found to explain the bloody stool He ask here to make alab evaluation for C B C &stool analysis On the third day she pass a fleshy, bulky bloody mass twice was passed one of them referred to pathology lab. & the patient was referred to be evaluated by surgeon who ask to repeat the ultrasound and the results referred to signs of intussusception but there is no any clinical signs of obstruction like vomiting or bouts of colic she referred to Cairo for further evaluation . Ultrasound was done for the third time but surprising us There is no any suggestive signs of intussusceptions so the decision was wait and see with the time no blood in stool general condition improved with time temperature disappeared So she was referred to PEDIATRIC G. I .T consultant for revaluation Drug induced GIT BLEEDING

Case presentation port said

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During the last decades advances in neonatal intensive care have led to an impressive decrease of neonatal mortality and morbidity. However, infectious episodes in the early postnatal period still remain serious and potentially life-threatening events with a mortality rate of up to 50% in very premature infants. [1, 2] The signs and symptoms of neonatal sepsis can be clinically indistinguishable from various noninfectious conditions such as respiratory distress syndrome or maladaptation. Therefore rapid diagnosis is crucial for preventing the child from an adverse outcome. The current practice of starting empirical antibiotic therapy in all neonates showing infection-like symptoms results in their exposure to adverse drug effects, nosocomial complications, and in the emergence of resistant strains. [3] Sepsis results from the complex interaction between the invading microorganism and the host immune, inflammatory, and coagulation response. [4, 5] Inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-15, IL-18, MIF) and growth factors (IL-3, CSFs), and their secondary mediators, including nitric oxide, thromboxanes, leukotrienes, platelet-activating factor, prostaglandins, and complement, cause activation of the coagulation cascade, the complement cascade, and the production of prostaglandins, leukotrienes, proteases and oxidants. [6] Laboratory sepsis markers represent a helpful tool in the evaluation of a child with clinical signs and complement the evaluation of a neonate with a potential infection. During the last decades efforts were done to improve laboratory sepsis diagnosis and a variety of the above mentioned markers and more were studied with different success. Despite the promising results for some of them current evidence suggests that none of them can consistently diagnose 100% of infected cases. C-reactive protein (CRP) is the most extensively acute phase reactant studied so far and despite the ongoing rise (and fall) of new infection markers it still remains the preferred index in many neonatal intensive care units.

C r p

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A voluntary, Internet-based reporting system for neonatal healthcare providers recently revealed that a broad range of medical errors occur in the NICU.[3] The most frequent error categories reported were wrong medication, dose, schedule, or infusion rate (including nutritional agents and blood products; 47%); error in administration or method of using a treatment (14%); patient misidentification (11%); other system failure (9%); error or delay in diagnosis (7%); and error in the performance of an operation, procedure, or test (4%). Errors in patient misidentification, for example, were a common cause of feeding a mother's expressed breast milk to the wrong baby.[3]

Common medical error in nicu

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Definition of High-risk Neonate: Any baby exposed to any condition that make the survival rate of the neonate at danger. Factors that contribute to have a High-risk Neonate: A) High-risk pregnancies: e.g.: Toxemias B) Medical illness of the mother: e.g.: Diabetes Mellitus C) Complications of labor: e.g.: Premature Rupture Of Membrane (PROM), Obstructed labor, or Caesarian Section (C.S).D) Neonatal factors: e.g.: Neonatal asphyxia

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According to the WHO, malnutrition is by far the biggest contributor to child mortality Under-weight births and IUGR (intra-uterine growth restrictions) cause 3 million child deaths a year. According to the Lancet, consequences of malnutrition in the first two years is irreversible. Malnourished children grow up with worse health and lower educational achievements. Malnutrition can exacerbate the problem of diseases such as measles, pneumonia and diarrhoea. But malnutrition can actually cause diseases itself , and can be fatal in its own right The term 'faltering growth' is widely used in relation to infants and young children whose weight gain occurs more slowly than expected for their age and sex. In the past, this was often described as a ‘failure to thrive’ but this is no longer the preferred term :- partly because ‘failure’ could be perceived as negative, but also because lesser degrees of faltering growth may not necessarily indicate a significant problem but merely represent variation from the usual pattern when measured against the standardized growth charts (WHO Growth Charts

Faltring growth

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Anemia can be seen in the emergency department both as a primary pathological process or secondary to both medical and surgical diseases. Moreover, acute anemia can occur in children who have been otherwise healthy, who have systemic disease, or who have known hematologic disorders. Anemia may indicate a disorder with a single hematopoietic cell line (eg, red blood cells) or may be associated with changes in multiple cell lines indicative of bone marrow involvement, immunologic disease, peripheral destruction of erythrocytes, or sequestration of cells. Independent of the etiology, prompt diagnosis is predicated on understanding the classifications of anemia, the associated presenting symptoms, and the proper ordering and interpretation of laboratory studies. This article will discuss the evaluation, proper classification, differential diagnosis, and initial management of acute anemia using cases representative of those that might be seen in the pediatric emergency department.

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Child with recurrent infections Prof osama arafa . Pediatrics PHD consultant& head of pediatric department Port Fouad hospital General secretary of Port Said Pediatrics Conference. Abstract The child with recurrent chest infections presents the clinician with a difficult diagnostic challenge. Does the child have a simply-managed cause for their symptoms, such as recurrent viral respiratory infections or asthma, or is there evidence of a more serious underlying pathology, such as bronchiectasis? Many different disorders present in this way, including cystic fibrosis, a range of immunodeficiency syndromes, and congenital abnormalities of the respiratory tract. In some affected children, lung damage follows a single severe pneumonia: in others it is the result of inhalation of food or a foreign body. The assessment of these children is demanding: it requires close attention to the history and examination, and in selected cases, extensive investigations. Early and accurate diagnosis is essential to ensure that optimal treatment is given and to minimise the risk of progressive or irreversible lung damage. The aim of this presentation is to examine the causes of recurrent chest infections and to describe how this complex group of children should be assessed and investigated.

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Pacifier &Thumb sucking is it good or bad? Many parents and doctors express concern over their child's thumb sucking or use of a pacifier. Often worried about affects on teeth and language development In fact, it has been shown that embryos actually suck on their thumbs while in the mother's womb. Thumb sucking and pacifier use both help children become comfortable with their environment, as well as offer children a sense of security. Most children should grow out of thumbsucking and pacifier use by age 3 or 4. As long as the habit is discontinued before their permanent teeth come in (around ages 4-5) your child will be fine. If, however, they continue this habit as their permanent teeth come in it is best to help your child discontinue their habit. In this presentation we will put spotlight on advantages and disadvantages of both pacifiers & thumb sucking trying to answer is it good or bad? Dr.Osama Arafa Abd EL Hamed M. B.,B.CH - M.Sc Pediatrics - Ph. D. Consultant of Pediatrics &Neonatology Head of pediatrics department Port-fouad hospital E mail; osama_1967@hotmail.com ¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬Tel:- Mob. 010 5196625 Clin. 066 3423252 Hom. 066 3412624

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