조재형가톨릭의과대학   伽서울성모병원   伽내분비내과   伽조교수   伽

우리   伽의학교과서의   伽세계진출,,

그   伽1155년의   伽기록

Ideas, dreams ---

0 5 10 15

years

도움이 지위

현실과 꿈의 시간차!

경험 약간의 돈

Human Network

A product

A result

Dreams come true!

우 리 도

갈 수 있 다낼

1981년 초등학생 4학년의 꿈!

1996년 의학과 4학년의 꿈!

An inspiration!

Systemic Lupus Erythematosus

Anemia (of chronic ds)†Hemolytic anemia† Leukopenia (<4000/µL)Lymphopenia (<1500/ µL)† Thrombocytopenia <100,000/ µL)Splenomegaly

Hematologic

Cognitive dysfunction (mc)Mood disorderHeadache, SeizurePsychosis, CVAPolyneuropathyAutonomic dysfunctionOptic neuritis, SAH

Neurologic (CNS lupus)

Thrombosis in vessels‡ Lupus anticoagulant (LA) and ‡ Anti-cardiolipin (aCL) ab : associated with clotting.Cerebral emboli

Vascular

Lumbar puncture (when the Dx of CNS lupus is in doubt or when infection is a possible cause of symptoms)MRI with contrast (acute and chronic lesion of SLE)CT (R/O bleeding or mass lesion)Neurologic problems usually improve with immunosuppressive tx : recurrence in 1/3 of patients (with the exception of deficits resulting from large infarcts)

Malar rashDiscoid rashPhotosensitivityOral ulcersAlopeciaVasculitis

Cutaneous

Arthral

gia, M

yalgi

a

Myopath

y

Nonero

sive

poly

arthrit

isMuscu

loskel

etal

Fatigue, malaiseFever, NauseaAnorexiaWeight loss

Systemic

Pleurisy, PericarditisMyocarditis, arrhythmiaEndocarditis, CAD (MI)Pleural effusionLupus pneumonitisHeart failure, Pulmonary hypertension*The most common cause of pulmonary infiltrate in patients with SLE is infection

Cardiopulmonary

Proteinuria >500mg/24hrCellular castsNephrotic syndromeRenal failureHematuria

Renal (lupus nephritis)

Rapidly deteriorating renal function and active urine sediment require prompt aggressive tx without biopsy

A slow rise in serum Cr. To 3mg/dL : should be biopsied

Pathology

Retinal vasculitis

Conjunctival/

episcleritis

Sicca syndrome

Ocular

Lupus peritonitis (nausea, diarrhea, vague discomfort)Vasculitis of intestine (the most dangerous) : presenting with acute crampy abd. pain, vomiting, diarrhea, : Intestinal perforation (immediate surgery)Pseudoobstruction (*surgery shoud be avoided unless frank obstruction is present)Acute pancreatitisElevated serum transaminase levels

Gastrointestinal

Mesangial or mild focal proliferative nephritis maintain good renal function (do not require treatment)Diffuse prolierative nephritis develop renal failure if untreated (require tx with high-dose glucocorticoid and cytotoxic agents)*A high proportion of sclerotic glomeruli : suggest that these patients are unlikely to respond to immnosuppressive tx and are candidates for dialysis ro trnasplantation

Hemolysis is usually responsive to high-dose GC * resistant case may respond to splenectomyLeukopenia is common but is rarely associated with infection : does not require treatmentSevere thrombocytopenia with bleeding or purpura should be treated with high-dose GC * If the platelet count fail to reach acceptable level in 2 weeks, cytotoxic drugs, cyclosporins, danazole, and/or splenectomy should be considered.

†

LA is recognized by prolongation of PTT and failure of added normal plasma to correct the prolongationLA, aCL : thrombocytopenia, recurrent venous or arterial clotting, recurrent fatal loss, vascular heart disease.LA is associated with hypoprothrombinemia or thrombocytopenia.Bleeding may occur.*Bleeding syndrome usually respond to GC. but clotting syndrome do not.

‡

Fertility rates : normalSpontaneous abortion and still birth are frequent (10-30%) ; Tx : low-dose heparin (e.g., 5000U S.C. twice a day) * if contraindicated to heparin, low-dose aspirin or low-to moderate dose glucocorticoid may be used.Glucocorticoid : do not cause fetal abnormality because corticosteroid are inactivated by placental enzymes,

SLE in pregnancyCaused by transmission of maternal anti-Ro across the placentaTransiet skin rash and (rarely) permanent heart heart blockTransient thrombocytopenia from maternalanti-PLT ab.

Neonatal lupus

If they fail to respond

J&J 2002

2001년 함께 꿈을 꾸다!

孔子는 登東山而小魯하시고 登太山而小天下

2002년 다시 시작된 작업!Reticulocyte production index

Index < 2.5 Index ≥ 2.5

Lead poisoning (rare in adults)

Sideroblastic anemia (some cases)

Thalassemia trait (reticulocyte count may be elevated)

Anemia of chronic disease (some cases)

IDA (severe)

Physiologic anemia

Iron deficiency (mild to moderate)

Mixed microcytic and macrocytic anemias

Anemia of chronic disease (most cases)

Myelodysplasia (most cases)

Myelophthisis

Myelofibrosis

Pure red cell aplasia

Renal insufficiency

Bone marrow aplasia/hypoplasia

Liver disease

Hypothyroidism

Myelodysplasia (some cases)

Prior cancer chemotherapy

Treatment with drugs that interfere with DNA sysnthesis and cell division

Folate def.

Cobalamine (vit B12)def.

[ Further evaluation ]

Low

Normal

High

Osmotic damage - Fresh water drowning

Infection - Malaria, Babesiosis, Bartonellosis, Clostridia toxin

Membrane abnormalities - Acanthocytes (spur cells) - Echinocytes (burr cells) - PNH - Thermal injury (burns)

Hypersplenism

Traumatic (microangiopathic and macroangiopathic) Hemolysis - TTP/HUS/HELLP - DIC - Vasculitis - Eclampsia - Malignant hypertension - Prosthetic heart valves - Arterial grafts

Immune hemolysis -Autoimmune -Drug-induced -Alloimmune

[ Further evaluation ]

Hemoglobinopathies -Thalassemias -Hemoglobin S,C,D,E

RBC Enzymatopathies -G6PD deficiency -Pyruvate kinase def.

RBC membranopathies -Spherocytosis -Eliptoctyosis -Stomatocytosis

Acquired

Inherited/Congenital

Hem

orrh

age

Serum iron, TIBC, ferritin,soluble transferrin receptor(± bone marrow iron stain)

Hemoglobin electrophoresis,hemoglobin A2 and hemoglobin F levels, globin DNA alalysis, globin chain systhesis ratios

PLT count, WBC count with differential, BM aspirate and biopsy

BM aspirate and biopsy(including Prussian blue stain of iron),karyotype analysis

BM biopsy with stainsfor collagen (trichrome stain)and reticulin (siliver stain)

Renal function test

Serum vit. B12 level, urine (± serum) methylmalonic acid level, BM aspirate, Schilling tests

Red blood cell folate level, serum folate level, BM aspirate

Reduction in serum haptoglobinPresence of urine hemoglobin and/or urine hemosiderinIncreased LDH and serum unconjugated bilirubin

Thyroid function test

Liver function test

[ General measures of hemolysis ]

Direct Coombs’ test, quantitation of red blood cell surface antibodies,cold agglutinin titer

Direct and indirect Coombs’ test, quantitation of red blood cell surface antibodies, cold agglutinin titier

Acid hemolysis (HAM) or sucrose hemolysis test, flow cytometry analysis of GPI-anchored cell surface proteins (e.g., CD55, 59)

History and physical exam. of hypertension, pregnancy, prosthetic heart valves or vascular grafts, systemic vasculitis, neurologic changes, fever?;Schistocytes, anemia, and destructive thrombocytopenia;BUN/Cr; Urinalysis; DIC study

IDA Anemia of chronic diseaseSerum iron Serum total iron-binding capacity Low normal -

Transferrin saturation Low normal -Serum ferritin Normal - Serum soluble transferrin receptor Bone marrow iron stores Iron-containing normoblasts in the bone marrow

Sear

ch b

leed

ing

focu

s and

trea

t

Hemolysis

+

MCVNo symptoms or signs of blood loss

Findings of acute or chronic blood loss on history or physical examiantion

Hemolysis or Hemorrhage

Differential diagnosis

J J&

Peak Bone mass

Factors affecting peak bone massGenderRace, Genetic factor, Gonadal steroidsGrowth hormone, Timing of pubertyCaclium intake, exercise

Osteoporosis2ndary causes (secondary osteoporosis) Hypogonadal state : Turner syndrome, Anorexia nervosa, Kleinfelter Endocrine dis: Cushing’s syndrome Hyperparathyroidism Thyrotoxicosis IDDM Acromegaly Adrenal insufficiency Nutritional and GI dis : Malnutrition Parenteral nutrition gastrectomy Reumatologic dis: RA, AS Hematologic : MM. Lymphoma, leukemia

Drgus : Glucocortuciud Cyclosporin Cytotoxic drugs Anticonvulsants Excessive alcohol Excessive thyroxine Aluminum Heparin GnrH agonist Lithium00

※ If estrogen deficiency : IL-1, IL-6, TNF ↑ → osteoclast mediated bone resorption ↑

; Vertebra fracture upper lumbar vertabra : most common Hip fracture Colles’ fracture : Early ambulation is recommended.

Fracture

Risk factors for osteoporosis fractureNonmodifiable Fracture hx as an adult Hx of fracture in first degree relative Female, Advanced age Caucassian race, Dementia

Modifiable Current cigarette smoking, Alcoholism Low body weight, Impaired eyesight Estrogen def, Recurrent falls Low calcium intake, Inadequate physical activity Poor health

DEXA(BMD) : T score <-2.5Biochemical markers : monitoring the responsiveness to treatment Bone formation markers

serum bone-specific alkaline phosphataseserum osteocalcinserum propeptide of type I procollagen

Bone resorption markers.

1. Women with no risk factors should begin therapy if their T score is -2 or below; and 2. Women with risk factors should begin therapy if their T score is -1.5 or below.

Glucocorticoid induced osteoporisus : inhibit osteoblast fuction, increase osteoblast apoptosis stimulation of bone resorption, increase of urinary calcium loss impairment of the absorption of calcium across the intestine : Bone loss – rapid loss first 6-12 months after start of glucocorticoid Tx :Risk facotrs reduction, Exercise Bisphosphonate (residronate) Calcium (1000mg) + calcitriol (0.5 – 1.0µg) Calcitonin

Antiresoptive drugHRT(ERT)†SERMCaclium : 1000=-1200mg of elemental cacliumBisphhosphonateVit D 20µg or 800 IUCalcitonin : might have analgesic effect

Formation stimulator Lowdose intermittent PTH Fluoride Anabolic steroid (mnostly derivatives of testosterone primarly as antiresorptive agents may also stimulate osteoblst acitivity)

: at age of 30-35 years

Type I osteoporosis : Estrogen ↓ ⇒ Ca resorption ↑ ⇒ PTH ↓ 1,25(OH)2D3 ↓Type II osteoporosis : 1,25(OH)2D3 ↓ ⇒ intestinal Ca absorption ↓ ⇒ PTH↑ ⇒ Ca resorption ↑

Dr u

g in

duce

d os

teo p

oros

is

Estrogen deficient women at clinical risk of osteoporosisVerterbral abnormalities on X-ray suggestive of osteoporosisGlucocoriticoid treatment equivalent to ≥7.5mg of prednisolone, or duration of therapy >3monthsPrimary hyperparathyroidismMonitoring response to an FDA-approved medication for osteoprosisRepeat BMD evaluation at >23-month intervals, or more frequently, if medically justified.

FDA-Approved Indications for BMD tests

Diagnosis

Treatment recommedations (from National Osteoporosis Foundation)

Trea

tmen

t

Risk factorsReduction

Exercise

Management of the fractures

Pharmacologic treatment

J J&

2003년 도전의 시작!

‘ 꿈은 매우 구체적이어야한다!’

1. 아마존닷컴에 꽂힌다.

2. 하바드의대 학생들이 우리책으로 공부하게한다.

Proposal

ToOxford

UniversityPress To

McGrawHill

꿈을찾아여행을 떠나다!

To England

8개월의 기다림

그리고,결과는?

이제 어떻게!

친구의 전화 한통!

무언가를할때

죽는 척이아니라

정말 죽을 것같아야한다!

Proposal in Korean

공보의군의관

임상강사

범문사 (현, E-public)

2004, 1월. 드디어 계약!

Adobe illustrator!?

미친 작업!

Wonju, 2004

또 한번의 여행!

To America

0

500

1,000

1,500

2,000

한국

몽골

타국

1쇄 2쇄

?

제2의 내과교과서

아직, 꿈은 이루어지지 않았다!

Get Friends!

130명의 참여

전문 illustrator의 참여

1,000 page분량

푸랑크푸르트 세계 도서전시회

LWW and Mcgraw Hill과 교섭중

2010.4.21. 2nd. Ed

2010.4.22. On the publication day

To Amazon

중앙일보, 2010.11.1.

Korea Herald, 2010.11.19.

새로운 시작을 꿈꾸며!

KOOB새로운 도전

iProducing & Sharing Anywhere

감사합니다!