Health is Wealth

Smoking accounts for 80 – 90% risk of developing COPD.

Only 15% of smokers clinically get COPD.

Caused by bronchial irritation and swelling of airway.

Chronic Compensated COPD
Dx

Best tool is pulmonary function testing (table 69-1)

ABG Hypoxia is main sign, increases with severity of disease.

CXR

R sided heart failure (Cor Pulmonal)

BNP (helps more to dif from CHF)

ECG or recent Echo with EF

Usually due to increased airway obstruction 2°

Increased bronchospasm

CV deterioration

Continued smoking, really, Smoking.

Noncompliance with medication.

Noxious / Environmental exposures

Clinical Apperance:

Dyspnea

Orthopnea

Pursed lip exhalation

Accessory muscles of resperation used.

Diaphoresis

Pt speaks in shorter increments as obstruction progresses

DX

Assesment of O2 status is Key.

Pluse ox ok but does not give PCO2 or pH.

ABG is best, PaO2 <60>

FEV1 <>

CXR

ECG could reveal concurrent disease process.

TX

O2 titrate to PaO2 >60 mmHg SaO2 >90%

Bronchodilators b2 agonist (albuterol, levalbuterol)

Anticholinergics Ipatropium Bromide 0.5 mg (atrovent)

Corticosteroids Prednisone 60 – 180 mg per/day for 7 to 14 days.

(methylprednisolone 60 -125 mg IV given in asthma exacerbations)

Thank you.

WHO’s Eastern Mediterranean Region is home to some of today’s most intractable

crises. Natural disasters, conflicts and other emergencies continue to affect

populations across the region, putting the health services under extensive strain.

Ladies and Gentlemen

We are all still living the tragedy of Gaza and the catastrophe resulting from the

destruction of the health facilities there. This is a violation of international law and

should be considered a war crime and a grave crime against health. We also still

remember the earthquake that hit Pakistan in October 2005. In a few seconds, out of

796 health facilities ranging from sophisticated hospitals to rural clinics,

388 were completely destroyed. The remaining facilities that were able to continue

functioning were utterly overwhelmed.

The health care workforce was also severely affected by this event.

Why should we invest in safe health facilities in emergencies?
WHO’s Eastern Mediterranean Region is home to some of today’s most intractable crises. Natural disasters, conflicts and other emergencies continue to affect populations across the region, putting the health services under extensive strain.
Ladies and Gentlemen
We are all still living the tragedy of Gaza and the catastrophe resulting from the destruction of the health facilities there. This is a violation of international law and should be considered a war crime and a grave crime against health. We also still remember the earthquake that hit Pakistan in October 2005. In a few seconds, out of 796 health facilities ranging from sophisticated hospitals to rural clinics, 388 were completely destroyed. The remaining facilities that were able to continue functioning were utterly overwhelmed. The health care workforce was also severely affected by this event.
In the past five years, over 800 health facilities were partially or fully damaged from several events within the region. They were earthquakes in the Islamic Republic of Iran and Pakistan, conflict in Iraq, Lebanon and Palestine, a cyclone in Oman and floods in Yemen. Natural disasters and all sort of emergencies can affect anyone, anywhere.
Although climate change and the subsequent warming of the planet may be gradual, the increasing frequency and severity of extreme weather events—intense storms, heat waves, drought and floods—will be abrupt and the health consequences will be acutely felt.
Health facilities are about more than just bricks and mortar. In addition to their physical structure, health facilities must have the functionality to continue providing services throughout and after the events in order to save lives. Functional collapse, not structural damage, is the usual reason for hospitals being put out of service during disasters.
A crisis happens when it is least expected, and we know that disasters can hit at any time. Saving lives can only be achieved if proper investments are made in emergency preparedness and training of the health workforce. Hospital failure and health system disruption during emergencies is as often due to system overload and lack of contingency planning as of physical failure. Staff training is just as important as physical protection.
Incorporating comprehensive disaster protection for earthquakes and extreme weather events into new building designs adds only an additional 4% to total costs. We must remember that when a hospital is out of service, many thousands of people are left without health care. In the long run, disruption of essential health services affects a country’s development potential.
Don’t let health facilities be another victim of emergencies.
Thank you.

MORPHOLOGICAL FEATURES

Gross
neuroblastomas are usually large,soft,grey and relatively well circumscribed;areas of hemorrhage,necrosisand calcification are often present.some time hemorrhage is so extensive as to mimic hematoma.cystic degeneration also occur.
Microscopy
The pattern of growth is vaguely nodular as a result of delicate,incomplete fibrous septa.the tumor cells are small and regular,slightly larger than small lymphocyte.Homer-wright’s rosettes are present,characterized by collection of tumor cells around a central area filled with a fibrillary material,which is mass of nuerites as revealed by silver stains.

ELECTRON MICROSCOPY
Ultra structurally , neuroblastoma cells are characterized by the presence of neuritis ,neurosecretory granules and synaptic endings the neuritis form a complex interdigitating meshwork in the centre of rosette
Immunohistochemistry
Neuroblastoma cells expresses neuron-specific enolase, neurofilaments, neurofilament-66/a-internexin, peripherin, chromogranin, synaptophysin, secretogranin 2, vasoactive intestinal peptide, microtubule associated proteins, NB 84, nerve growth factor receptors and other neuron related antigens including cell surface ganglioside GD2. Expressoin of Insulin- like growth factor 2 is associated with a lobular growth pattern and good cytological differentiation.
Neuroblastoma produce catecholamines which can be demonstrated in sections or touch preparations by the twchnique of formaldehyde- induced fluorescence.
Chromosomal and molecular markers
During last 2 decade, many chromosomal and molecular abnormalities have been identified in neuroblastoma. these biologic markers have been evaluated to determine their value in assigning prognosis,and some of these have been incorporated in to the stratergie sused for risk assignment
The most important of these biologic markers is MYCN ,which is over expressed oncogene in neuroblastoma with amplification of distal arm of chromosome 2.it is amplified in approximately 25% of do novo cases and is more common in patients with advanced-stage disease,and is marker of poor prognosis.in contrast to MYCN ,H-ras oncogene correlates with lower stage of the disease.
Deletion of short arm of chromosome 1 is most common chromosomal abnormality, which confers poor prognosis. Other alleic losses of chromosomes 11q, 14q, 17q and gain of chromosome 1 have been reported.
DNA index is another useful test that correlates with response to therapy in infants. Look.et al demonstrated that

Lab studies
• General laboratory studies should be routinely obtained in children suspected of having neuroblastoma.
•
o A CBC count should be obtained to determine if the child has anemia, which typically does not occur until the tumor has become widely disseminated.
o Once dissemination occurs, abnormalities in findings of coagulation studies (prothrombin time [PT], activated partial thromboplastin time [aPTT]) may secondary to liver involvement. Thrombocytopenia due to overwhelming bone marrow involvement may also be present.
o The erythrocyte sedimentation rate, a nonspecific acute-phase reactant, is elevated in classic neuroblastoma.
• Specific laboratory studies should be obtained when the diagnosis of neuroblastoma is considered.
•
o Metabolic tumor by-products are useful as diagnostic inclusion criteria for detecting neuroblastoma.
o Elevated metabolic catecholamine by-products can be detected in the urine of patients with neuroblastoma.
o Phenylalanine and tyrosine are catecholamine precursors, which are converted through a sequence of enzymatic events to dihydroxyphenylalanine (DOPA), dopamine, norepinephrine, and epinephrine.
o DOPA and dopamine are metabolized into their final product, homovanillic acid (HVA), while norepinephrine and epinephrine are metabolized into vanillylmandelic acid (VMA).
o Ninety percent of neuroblastoma tumors secrete these by-products. This fact becomes clinically relevant because children with dedifferentiated tumors excrete higher levels of HVA than VMA. This occurs because dedifferentiated tumors have lost the final enzymatic pathway that converts HVA to VMA. A low VMA-to-HVA ratio is consistent with a poorly differentiated tumor and indicative of a poor prognosis.
o Neuroblastoma cells lack the enzyme that converts norepinephrine to epinephrine. Despite this fact, elevated levels of norepinephrine are not identified in the serum of patients with neuroblastoma. This might be explained by at least 2 processes—(1) norepinephrine may be catabolized within the tumor; or (2) tyrosine hydrolase, the initial enzyme in catecholamine synthesis, is subject to a negative feedback loop by norepinephrine. For either or both reasons, norepinephrine does not reach detectable serum levels.
o A LaBrosse VMA spot test may be used to screen patients in certain institutions. It is economical but has low sensitivity and specificity.
o High-performance liquid chromatography has a much lower false-positive rate and is more sensitive than the LaBrosse VMA spot test, but its only drawback is that it is more expensive and is therefore often used only to confirm a positive result on spot test.
• Nonspecific tumor markers can be identified in patients with neuroblastoma.
•
o Neuron-specific enolase (NSE), lactic dehydrogenase (LDH), and ferritin are markers useful in the identification of active disease, as well as in prognostication.
o Approximately 96% of patients with metastatic neuroblastomas demonstrate an elevated NSE level, which has been associated with a poor prognosis.

Imaging studies
Radiographic assessment is recommended in all infants and children with an abdominal mass. The standard diagnostic imaging modalities include plain abdominal radiography (kidneys, ureters, bladder [KUB]), renal/bladder ultrasonography, bone scintigraphy, and CT scanning or MRI.
• KUB most commonly reveals finely stippled calcifications of the abdomen or posterior mediastinum.
• Renal/bladder ultrasonography improves the diagnostic evaluation and is probably the single best imaging modality to obtain. Ultrasonography is noninvasive and provides relevant information regarding the laterality, consistency, and size of the mass.
• Abdominal CT scanning or MRI usually follows ultrasonography. Both of these studies are more invasive, in that they require general sedation for young children. The benefit is that they enhance the ultrasonographic findings by providing information about regional lymph nodes, vessel invasion, and distant metastatic disease.
• Bone scintigraphy and a skeletal survey to detect cortical bone disease are helpful in the diagnosis of neuroblastoma. Metaiodobenzylguanidine (MIBG) is a compound taken up by catecholaminergic cells that competes for uptake even in neuroblastoma cells. In this way, MIBG is quite sensitive and specific in the detection of metastasis to bones and soft tissue, with highest sensitivity (91-97%) in the detection of bone deposits. Bone scintigraphy using 99Tc diphosphonate and a skeletal bone survey to detect cortical bone disease are essential if MIBG scintigraphy results are negative in the bone. MIBG is recommended for re-assessment both during and after therapy in high-risk patients with MIBG-avid disease at diagnosis.
• Expression of somatostatin (SS) receptors has been described in neuroblastoma cell lines and tumors. Studies have shown that these tumors can be successfully targeted with radioactive SS analogs as a method of detection. Currently, the indication for radio-labeled SS analog in children with neuroblastoma is not well-defined because this method is less sensitive than MIBG scan (64% vs 94%). However, because neuroblastoma SS receptors are associated with favorable clinical and biological prognostic factors, radio-labeled SS analog could provide valuable information. In fact, improved survival has been found in patients with SS receptor–positive neuroblastoma. However, more studies need to be performed to confirm the benefits of SS receptor scanning.

The international neuroblastoma staging system (INSS)

Stage 1 Localized tumour with complete gross excision, with or without microscopic residual disease; representative
ipsilateral lymph nodes negative for tumour microscopically (nodes attached to and removed with the primary
tumour may be positive).
Stage 2A Localized tumour with incomplete gross excision; representative ipsilateral nonadherent lymph nodes negative for tumour microscopically.
Stage 2B Localized tumour with or without complete gross excision, with ipsilateral nonadherent lymph nodes positive for tumour. Enlarged contralateral lymph nodes must be negative microscopically.
Stage 3 Unresectable unilateral tumour infiltrating across the midline (vertebral column) with or without regional lymph node involvement; or localized unilateral tumour with contralateral regional lymph node involvement; or midline tumour with bilateral extension by infiltration (unresectable) or by lymph node involvement.
Stage 4 Any primary tumour with dissemination to distant lymph nodes, bone, bone marrow, liver, skin and/or other organs (except as defined for stage 4S).
Stage 4S Localized primary tumour (as defined for stage 1, 2A or 2B), with dissemination limited to skin, liver and/or bone marrow (limited to infants <1 year of age).

History

Neuroblastoma was first described by Sir Rudolf Virchow in 1864 and at that time it was

referred as glioma.

In 1891 Marchand histologically linked Neuroblastoma to sympathetic ganglia.

Herxheimer,In1914 gave the substantial evidence of neural origin by demonstrating the fibrils of the tumor stained positively with special neural silver stains.

In 1927, Cushing and WOlbach first described the transformation of malignant Neuroblatoma

into its benign counterpart , ganglioneuroma.IN 1957, Mason published report of a child with

Neuroblastoma whose urine contained pressor amines which helped to understand the possible

origin from sympathetic neurons.

causes:

The etiology of Neuroblastoma is not well understood.

Several risk factors have been prposed and are the subject of ongoing research.

Due to characteristic early onset , many studies have focused on parenteral factors

around conception and during gestation.Factors investgated have included

occupation , that is exposure to chemicals in specific industries,smoking,

alcohol consumption, use of medicinal drugs during pregnancy.

However results have been inconsistent.

Neuroblastoma can exhibit familial incidence .

It can be associated with Beckwith-wiedemann syndrome,

HIrschprungs, Neurofibromatoses or occur as a complication of fetal hydantoin syndrome.

Neuroblastoma has been called the great mimicker because of its myriad clinical

presentations related to the site of tumor, metastatic disease and its metabolic tumor

byproduct.The most common site of neuroblastoma is abdomen arising either in the

adrenals or less commonly in the para midline sympathetic chains.

Other sites being neck, mediastinum, pelvis.Neuroblastoma is one of the rare human

malignancies known to demonstrate spontaneous regression from undifferentiated to

a completely benign cellular appearance.

The initial symptoms are often vague and often include fatigue,

loss of appetite and fever.Later symptoms depend on tumor location.

The most common finding on physical examination is a non tender ,

firm,irregular abdominal mass.at the time of diagnosis ,the site of neuroblastoma

predictably age dependant.Infants often present with compression of sympathetic

ganglia in thoracic region which might result in Horner’s syndrome

(mioses, anhydrosis and ptosis)or Superior vena cava syndrome.

Older children typically present with abdominal complaints.

More than 50% of patients presenting with neuroblastoma have metastatic disease,

which resulted in syndromes. Pepper Syndrome occurs in infants with

metastatic deposits in liver. it generally confers a better prognosis, however,

may die of massive hepatomegaly,respiratory failure and overwhelming sepsis.

Blue-berry muffin babies are infant in whom neuroblastoma has become metastatic

to random subcutaneous sites.Opsoclonus/myoclonus ,thought to be

paraneoplastic ,perhaps autoimmune.

widespread metastasis of neuroblastoma to bone may result in Hutchinson

syndrome. It results in bone pain ,limping and pathological fractures.


Most neuroblastomas produce catecholamines as metabolic by-products resulting,

in some patients, Kerner-morrison syndrome, causes intractable secretory diarrhea,

leading to hypovolaemia ,hypokalaemia, prostration. It is secondary to vasoactive

intestinal peptide(VIP) tumor secretion.


This syndrome more commonly associated with Ganglioneuroblastoma /

Ganglioneuroma typically resolves with complete removal of the tumor.

85% of deaths in children under 5 years old

Economic cost

Direct: USD 12 billion per year in direct losses,lost 1.3% of GDP growth per year for Africa.

For Nigeria alone the direct loss to the economy is estimated at GBP530 million

Burden
35.4 million Disability Adjusted Life Years (sub-Saharan Africa)

Cost per DALY averted

USD 2-24 (sub-Saharan Africa)

Cost of malaria

Around 40% of public health spending in sub-Saharan Africa20-50% of inpatient admissionsUp

to 50% of outpatient visits

Average household spending

Over 10% of yearly spending in AfricaDirect costs $0.41 in Malawi, $7.38 in Ghana

Financial need to tackle Malaria

2009: USD 5.335 billion2010: USD 6.180 billion2011-2020: USD 5.126 billion (average)

Annual funding
2007: USD 1.107 billionFunding gap: USD 4,266 billion
Required investment in research (10 years)
USD 8.9 billion

Current level of coverage

Treatment: more than 100 millionNets: 66.2 millionDiagnostics: 16 million rapid diagnostics

tests delivered in 2006 among which 11 million in Africa

Required coverage by 2010
Protective nets: 730 million long-lasting insecticidal nets (LLINs). (350 million in Africa)Indoor spraying with insecticide: 172 million households need annual spraying.Preventive treatment for pregnant women: 25 million pregnant women annually.Diagnostic tests: approximately 1.5 billion annually.Drugs: 228 million doses of ACTs are needed to treat P. falciparum annually; additional 19 million doses of chloroquine and primaquine are needed annually for P.vivax.

Impact of full coverage

Up to an estimated 4.2 million lives could be saved by 2015 in the 20 highest burden African countries alone.

Malaria and humanitarian crises
Up to 30% of malaria deaths in Africa occur in the wake of war, local violence or natural disasters.

MDGs that could be impacted by addressing malaria problem
MDG 1 – Eradicating extreme poverty and hungerMDG 2 – Achieve universal primary educationMDG 4 – Reduce child mortalityMDG 5 – Improve maternal healthMDG 6 – Combat HIV/AIDS, malaria and other diseasesMDG 8 – global partnerships for development and access to affordable drugs

Costs of interventions
Long-lasting insecticidal net: $10 (includes the net, distribution, teaching usage and monitoring usage)Course of ACTs for adult: $6

Impact in tackling malaria

Eritrea, Rwanda, and Sao Tome and Principe reported declines in the number of cases and deaths of 50% or more between 2000 and 2006–2007 following high coverage of control activities. In addition, 22 countries outside of Africa reported declines of 50% or more in malaria cases and deaths between 2000 and 2006.