Circulatory changes in newborn

During in-utero life, the right atrial pressure is greater than left atrial pressure, since there's less pulmonary blood flow, and greater amount of systemic and placental venous return to right atrium.

Hence, the flap valve of foramen ovale remains patent, allowing blood flow from right to left atrium.

Once the baby takes his/her first breath, the pulmonary vascular resistance decreases, amount of pulmonary blood flow increased by 6 folds. In addition, placental venous return is excluded from the venous return to right atrium, hence left atrial pressure is now greater than right atrial pressure.

This results in obliteration of foramen of ovale.

What happens in IUGR the ratio of OFC and Chest circumference?

b. When is the peak growth velocity in adolescent girl?

c. What is the probable age of child who climbs with alternate steps but can not say his name and sex?
d. What is the probable age of a child who hold head at 90 degree?
e. A baby has unilateral moro with positive palmar grasp reflex where is the site of lesion?
f. A child can walk down stairs with alternate steps holding on to the rail. What is the probable age?
g. At what age the moro reflex disappears?

h. Earliest hormonal change to occur in puberty?

i. What is short stature?

a. Fatty liver, patchy depigmentation of hair and oedema is diagnosis of:
b. A child with alopecia, eczematous lesion over mouth and genitalia and hypogonadism is likely to have suffered from:
c. The characteristic three radiological feature of rickets is:
d. what is the calorie requirement for a severely malnourished child?
e. What are the percentage of calorie from diet in balance diet?
f. How breast feeding offers lower risk of infection?
g. What are iron dependent enzymes?

a. A child aged two years presents with anemia. Peripheral smear shows target cells and hypochromic/microcytic picture with Hb of 6gm. There is a positive family history. The next investigation of choice is:
Hb electrophoresis.

b. Feature of Fetal RBC is:
Alkali denaturation resistance.

c. As per WHO for infants less than 6 months, the Hb cut off level for anemia is:
11.5gm/L

d. What percentage of children between 6-23 months suffer from anemia in Nepal?
20%

e. What is the commonest cause of anemia in Nepal?
Nutritional anemia

f. What is the dose of oral iron to treat iron deficiency?
6mg/kg of elemental iron.

g. What are the three causes of hypochromic microcytic anemia?
Iron deficiency/ thalassaemia/ lead poisoning.

h. What are three causes of normochromic anemia with low reticulocyte count?
Leukemia/chronic infection/pure RBC anemia.

i. What further two test you will do for a child having normochromic anemia with high reticulocyte count?
Coombs test and hemoglobin electrophoresis.

j. What is the most likely diagnosis of a child whose total count is 2,500/cmm, platelet 60,000/cmm, RBC:200,000/cmm and no lymphadenopathy and hepatosplenomegaly?
Aplastic anemia.

k. What is the most likely diagnosis for a child with anemia, uremia, thrombocytopenia and raised FDP?
Hemolytic uremic syndrome.

l. What two investigations is done for bleeding disorders?
Bleeding time and clotting time.

m. What three tests are performed for vascular and platelet defects?
Platelet count/ Hess test/ bleeding time.

n. What three tests are assessed for diagnosing coagulation defect?
APTT/PT/Thrombin time.

o. Tell three clinical signs that differentiates platelet or vascular defects from coagulation defects?
Superficial and deep hemorrhages/ superficial bleeding arrested by pressure/ spontaneous bleeding are small and multiple.

p. Tell five causes of purpura?
ITP/leukemia/HSP/aplastic anemia/drugs/SLE/sepsis.

q. What is the desired rise of a coagulation factor required for the control of bleeding in a hemophilic child with single hemarthrosis?
30%.

r. Tell three complications of transfusion reaction?
Febrile reaction/allergic reaction/circulatory over load/ Hemolysis.



Tags: ITP, leukemia, HSP, aplastic, anemia, drugs, SLE, sepsis.

Mysterious,enigmatic and evanescent,the Neuroblastoma(NBL) is the 3rd most common paediatric tumour.It constitutes 10% of all childhood carcinomas and the survival rate is <30%.>1kg in weight.

Microscopically,masses of undifferentiated small,round cells (neuroblasts)are seen.Fibrils form longitudinal bundles or round whorls around cell masses giving a pseudorosette appearance (Homer Wright).
Better differentiated lesions contain more large cells with vesicular nuclei and prominent nucleoli-designated as ganglioneuromas.Large tumours show wide-spread necrosis and calcification.

Spread:
Hematogenous spread is common.
Bone(30%)
liver (20%)
Skull or brain (11%)
Lungs (9%)
Special predeliction exists for mets in the orbit causing proptosis with peripheral haemorrhage.

IN A CASE OF PROPTOSIS IN A YOUNG CHILD,THE CLINICIAN MUST EXAMINE ABDOMEN TO EXCLUDE NEUROBLASTOMA.

Mets in skull from adrenals occur through vertebral system of veins.

Lymphatic spread is late and involves regional nodes(25%) and cervical nodes(5%).

Clinical features:
Abdominal mass (asymptomatic in 2/3 rd patients)is commonest symptom .There may be weight loss,fever,vomitting and abdominal pain.
Pallor and pancytopenia may be present due to bone marrow involvement.

liver enlargement may be due to mets.Mets in skull may lead to swelling of head,proptosis with or without ecchymosis of the lids (Raccoon eyes).Occasional blindness and bone pain may be seen.

As NBL also originate in paraspinal ganglia,they may invade through the neural foramina and compress the spinal cord causing muscle weakness and sensory symptoms.

Due to paraneoplastic syndrome there may be cerebellar ataxia,involuntary movements and nystagmus-DANCING EYES AND FEET SYNDROME.

Rarely severe watery diarrhoea due to secreation of VIP maybe seen.

Posterior mediastinal mass and lung mets may lead to Horner's syndrome,dyspnoea or pneumonia.

SKIN has a typical BLUEBERRY MUFFIN appearance due to mets.

Opsoclonus/Myoclonus may be seen with pervasive and permanent neuro and cognitive deficits and psychomotor retardation.(immuological injury)

Cervical tumours may be palpable or actually visible.They may cause stridor or dysphagia

Criteria for diagnosis:(one out of the two)
1.Unequivocal pathologic diagnosis made from tumour by Light microscopy(with or without immunohistochemistry,electron microscopy or increased serum catecholamines)
2.Combination of Bone marrow aspirate/biopsy containing unequivocal tumour cells and increased level of serum/urinary catecholamines.


International NBL staging system:

Stage I Localised tumour with complete gross excision with or without microscopic residual disease,representative ipsilateral lymph nodes -ve for tumour microscopy.(nodes attached to or removed with primary tumour may be +ve)

Stage 2a Localised tumour with incomplete gross excision,representative ipsilat. non-adherant l.nodes -ve for tumour microscopically

Stage 2b Localised tumour with or without complete gross excision with ipsilat. non-adherant l.nodes +ve for tumour;enlarged contralateral l.nodes must be -ve microscopy.

Stage 3 Unresectable U/L tumour with C/L regional lymph node involvement or midline tumour with B/L extension by infiltration(unresectable) or by l.node involvement.

Stage 4 Any primary with dissemination to distant l.nodes,bone,bone marrow,liver ,SKIN or other organs.

Stage 4s Localised primary tumours(as in stage 1,2a,2b) with dissemination to SKIN ,liver and /or bone marrow (limited to infant epinephrine or NE is produced.
Therefore HVA (Homo vanillic acid) is raised and more specific than the increase in VMA.
LFT is not of much value though even in hepatic mets.

Also important markers are:
LDH>1500 IU/ml
Serum Ferritin>142ng/ml
Neuron specific enolase>100ng/ml
(to be correlated with advanced disease and decreased survival)

Staging work-up:
Chest X-ray
Bone marrow biopsy
radionucleotide scans to search for mets.
(Any abnormality on chest X-ray to be followed up with CT)

MIBG scan is the single best method to document presence of Metastasis.

Abdomen CT -may show occasional obstruction of ureter and displacement of intact kidney .

Open biopsy.


Treatment:
The treatment depends on the stage of the tumour.

Stage I Total excision alone.
Stage II Total excision +/- Post-operative radiotherapy and /or chemotherapy

Stage III Resectable tumours:Excision +multidrug chemotherapy+radiotherapy

Unresectable: Cytoreduction with chemotherapy and radiotherapy,followed by excision of the shrunken tumour.

Stage IV Combination chemotherapy.Attempted excision of residual tumours may be done in those responding to chemotherapy.

Stage IVs Excision of the primary tumour.
Occasionally the patient develops resp.distree due to rapidly enlarging tumour.Rx is low dose irradiation.Alternatively,the abdominal cavity is enlarged using sialastic patch in abdomen wall (as in gastroschisis/giant exomphalos).

Standard chemotherapeutic agents used:Cyclophosphamide,Vincristine.
Other recently tried drugs:Adriamycin,Cisplatin,Melphalan and Ditriazoimidazole carboximide.

However the results of chemo and radiotherapy are disappointing.

New approaches are 1.High dose chemotherapy
2.Total Body Irradiation
3.Allogeneic or autologous bone marrow transplantation.

Before re-infusion, autologous bone marrow may be 'cleaned' of tumour cells by treatment with cytotoxic agents couples to monoclonal antibodies directed against neuroblastoma cells.

Tumour cells may be extracted from the marrow by magnetic separation after application of magnetic beads coupled to monoclonal antibodies by COUNTERFLOW CENTRIFUGAL ELUTRIATION technique.

'Intracellular 'radiotherapy is based on affinity of radioactive I131 MIGB to tumour tissue.


Prognosis:

3 year survival for all stages is 30-50%
Patients 1year,low n-myc
>1 year,amplification of n-myc,
favourable biology

IVs favourable biology


Intermediate III 1 year,favourable biology

IVs low n-myc


High II > 1year,all unfavourable
biology

III 1year,unfav.biology

IV 1 year

IVs amp n-myc

Poor prognostic factors:-
Unfavourable biology
Primary abdominal lesion
High neuron specific enolase
High serum ferritin
Low ratio of VMA to HVA
n-myc amplification
Gain of genetic materialfrom chromosome arm 17q associated with chr.1p deletion
Multi-drug resistant protein

Expression of TRK is inversely associated with n-myc and carries good prognosis.

Diploid tumour carries unfavourable while hyperploid carries favourable prognosis.

Classification By Shimada et all deals with prognostication based on degree of differentiation,mitotic karyorrhexis index,presence/absence of stroma.


Epilogue:As we come to the end of unravelling most of the secrets of Neuroblastoma ,we must understand that this is still a mystery tumor .We are still not totally in a position to battle this neoplasm.Thus this is a challenge to the future generation of surgeons and researchers to come up with a cure.

• A disorder of chromosome 15
  

• Prevalence: 1:12,000- 15,000 (both sexes, all races)

Major characteristics: hypotonia, hypogonadism, hyperphagia, cognitive impairment, difficult behaviors

Major medical concern: morbid obesity

The genetic cause is loss of yet unidentified genes normally contributed
by the father. Occurs from three main genetic errors: Approximately 70%
of cases have a non-inherited deletion in the paternally contributed
chromosome 15; approximately 25% have maternal uniparental disomy
(UPD)—two maternal 15s and no paternal chromosome 15; and 2–5 %
have an error in the "imprinting" process that renders the paternal
contribution nonfunctional.

Diagnostic testing: Individuals who have a number of the clinical
findings should be referred for genetic testing. DNA methylation
analysis confirms diagnosis of PWS. FISH and DNA techniques can identify
the specific genetic cause and associated recurrence risk. (See ASHG/ACMG
Report, Am J Hum Genet 58: 1085, 1996.) Patients who had negative
or inconclusive tests with older techniques should be retested.



Major Clinical Features:

Neonatal and infantile central hypotonia, improving with age

Feeding problems and poor weight gain in infancy
Excessive or rapid weight gain between 1 and 6 years of age; central obesity in the absence of intervention

Distinctive facial features—dolichocephaly in infants, narrow face/bifrontal diameter, almond-shaped eyes, small-appearing mouth with thin upper lip and down-turned corners of mouth

Hypogonadism—genital hypoplasia, including undescended testes
and small penis in males; delayed or incomplete gonadal maturation
and delayed pubertal signs after age 16, including scant or no
menses in women

Global developmental delay before age 6; mild to moderate mental
retardation or learning problems in older children

Hyperphagia/food foraging/obsession with food

Minor Features

• Decreased fetal movement, infantile lethargy, weak cry
• Characteristic behavior problems—temper tantrums, violent outbursts, obsessive/compulsive behavior; tendency to be argumentative, oppositional, rigid, manipulative, possessive, and stubborn; perseverating, stealing, lying
• Sleep disturbance or sleep apnea
• Short stature for genetic background by age 15
• Hypopigmentation—fair skin and hair compared with family
• Small hands and/or feet for height age
• Narrow hands with straight ulnar border
• Eye abnormalities (esotropia, myopia)
• Thick, viscous saliva with crusting at corners of the mouth
• Speech articulation defects
• Skin picking