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2016年12月5日 星期一

[醫如往常] Senior Clerkship Day 96: Lab Medicine: Metabolic disorder & Lab Diagnosis

Metabolic disorder & Lab Diagnosis呂醫師

Hypoglycemia
Palpitations, tremor, anxiety

Hunger, diaphoresis, paresthesias

Wipple's triad
  • Symptoms
  • Low Glucose level
  • Relief after treatment

Causes
Drug
Hormone deficiency
Critical illness
Nesidioblastosis
Insulinoma
  • 72 hours fasting
  • Glucose<45 mg/dl
  • >3uIU/ml
  • C-peptide>0.6
  • BHBA<2.7

Autoimmune
Non-beta-cell tumors, IGF2
Alimentary or reactive, dumping
  • 5hr OGTT
  • Idiopathic
  • Alcohol
  • Treat wt alpha glucodase

全大腸切除治療慢性便秘，但可以能造成反應性低血糖
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Acrobose 延遲吸收，從dudenum改成terminal ileum吸收，阻斷餐後低血糖

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[醫如往常] Senior Clerkship Day 96: Lab Medicine: ERCA mutation

ERCA mutation molecular diagnosis 俞教授

Ovarian cancer 2nd most common
15% familial BRCA1, 2
No hot spot
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BRCAness phenotype
Platinum
PARP inhibitor
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Oraparib 亞洲上市
台灣沒有

Hazard ratio 0.35
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>3000 kinds

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Germline 18%
Somatic 7% both alleles mutation in cancer cells
  • Mutation >50%
  • Wild type homozygous mutations
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Capture-based method (ion torrent)
Long range PCR， 分成十段overlap 10k segments

Singapore也要送臺灣做NGS
台灣可以做tissue, 很先進
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大部分用MiSeq
Illumina 只能用blood, 不能tissue
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Setup of BRCA Database

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Founder mutation
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五階mutation
  1. Pathogenic 用藥很有效
  2. Pathogenic-like
  3. Variant of uncertain genecity 人數最多
  4. Non-pathogenic
  5. Normal-like
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BRCA functional mutation: positive
Other mutation 只能註記有
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之後主流
Immunooncology (IO)
Head and neck, 人數跟lung相當
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IHC Synchronization也是努力的目標
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研究比較有信譽
  • 中科院
  • 浙江
  • 華西
  • 復旦
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協和沒有Protocol
data就出來了
data跟西方一模一樣

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[醫如往常] Senior Clerkship Day 96: Lab Medicine: Diagnostic Endocrinology

Diagnostic Endocrinology
邱醫師
Growth hormone
先跑兩圈再抽血
增加測到的機率
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Cortisol 用米彩頭 agar tube
ACTH 用EDTA管+冰浴
IPSS (Inferior petrosal sinus sampling) 管子不要弄錯
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Cortisol
早上0800: 1
下午1600: 1/2
晚上2000: 1/4
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Midnight salivary cortisol 國外才有
只能測Hypercortisolism
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Package insert
看檢驗有哪些干擾

Dexamethasone 不會干擾cortisol測定
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Urinary free cortisol 只能篩檢 cushing
Serum >25 ug/dl 才會漏到尿中

24 hours
50-100ug borderline
>100ug positive
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Overnight dexamethasone suppression test
Cutoff: 2 ug/dl
Borderline: 2-5 µg/dL

CYP3A4 inducer
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現在只做High dose
Pituitary or ectopic
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Adrenal insufficiency
Cortisol <5  µg/dL
5-10 borderline
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Cushing
Loss of diurnal pattern

Pituitary MRI
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Ectopic
  • Small cell lung cancer
  • Parathyroid
  • Thymic cancer
  • Pancreas NET
  • Carcinoid
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Adrenal medulla
24hr urinary VMA(vanillylmandelic acid) HPLChigh-performance liquid chromotography (HPLC) >7.0 mg/24h
24-hour Urinary catecholamines:100 g/24h
  • Epi>20g/24hr
  • NE>80g/24hr
24hr urinary metanephrines 要在基因醫學部免費驗mass
>2 mg/24h
(metanephrine >0.4 mg/24h, normetanephrine >0.9 mg/24h)

Plasma metanephrines
  • NMN <112 ng/L and MN <61 ng/L: exclude pheo
  • NMN >400 ng/L or MN >236 ng/L: high probability of pheo


Clonidine suppression test
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Catecholamine axis: ARB ACEi不會影響
Mineral axis: 只有alpha blocker不會影響

也可以直接自費CT 避免風險
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2016年12月4日 星期日

[醫如往常] Senior Clerkship Day 94: Quality Control

    20161124 Quality Control
    NTUH每日6000～8000件
    Quality
    操作型 多少時間內可以檢出
    內部型 satisfication of the needs and expectations of customers 零檢出

    Insurance
    Media
    Associations
    Cost effectiveness

    林院長 三聚氰胺 下台

    Contact 脈絡
    ------------
    LC MASS
    HPLC

    ------------
    TSH

    Low T3, T4 syndrome
    ------------
    中華民國行業標準分類
    服務業Q86
    ------------
    唐醫師在北京兩年
    建郭台成骨髓庫

    ------------
    ANCOVA

    ------------
    服務滿意 死亡率上升
    兩種解釋
    1. 會吵的有糖吃
    2. 不告知重症滿意度高， 死的快
    ------------
    醫療不是服務業的原因
    1. 不能拒絕病人
    2. 很多事不能用錢解決
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    醫師信任度僅次於家人
    ------------
    Co-efficiency of variance=SD/Mean
    2 COA 95%
    ------------
    Total error=Accuracy+2SD

    TEa
    Allowance 人為定義
    ------------
    Internal QC
    Levey Jenning Control chart

    ------------
    Medical method 引用數最大的論文

    ------------
    Proficiency testing
    Target value
    • Gold standard
    • Artificial 調配
    • 所以檢驗的Mean
    ------------
    Lab error
    Murphy law
    Swiss cheese

    ------------
    為了節省沒用到的管子
    條碼貼兩層
    太敏感可能讀到下面那層
    ------------
    沒有手圈
    可能抽到家屬的血
    ------------
    管子抽血順序弄錯
    EDTA

    ------------
    污染菌
    到底要不要cover
    不cover法律問題
    Cover 防衛性醫療， 無法治療病人
    ------------
    Accreditation
    PDCT
    Plan
    Do
    ------------

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[醫如往常] Senior Clerkship Day 93: Lab Medicine: 藍紅黃綠紫灰黑

20161123
李醫師
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Good Marker
  • Sensitivity
  • Specific
  • Low molecular weight
  • Long half life
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Syncope
VT
  • >120 /min
  • 1/3
  • AV dissociation
  • Capture beat
  • Fusion beat

V1 rbbb
Lbbb
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Pacemaker
  • Subclavian vein
  • LBBB
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ANB monocyte
CAE eosinophil
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Cytospin
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AML
Cd34 immature
Cd11b, 15 mature
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A Coulter counter [1] [2] is an apparatus for counting and sizing particles suspended in electrolytes. It is used for cells, bacteria, prokaryotic cells and virus particles.[3]
A typical Coulter counter has one or more microchannels that separate two chambers containing electrolyte solutions. As fluid containing particles or cells is drawn through each microchannel, each particle causes a brief change to the electrical resistance of the liquid. The counter detects these changes in electrical resistance.
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CML
Basophil
Eosinophil

Megakaryocytes small
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藍紅黃綠紫灰黑
  • Blue 3.2% citrate (以前用3.6%): PT, aPTT 
  • 採血量較少時，依1:9比例使用。
  • 紅: 生化
  • 黃
  • 綠色 heparin: NH3, LDH
  • Purple EDTA: CBC, Hb 電泳, HbA1C
  • Gray NaF EDTA: glucose
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ACD 淺黃 lymphocytes
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胡助教授
血小板生命 兩周
全血 四個月

Fy-ab (-) 有anti-malaria效果，非洲人很多
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MCHC 正常值33+-3 代表RBC central pale zone的比例
RDWCV 正常值13+-1.5
Ret 正常<2%
IRF(Immature Retic Fraction)=(HFR+MFR)/Reticulocyte 正常<20%
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遇到Platelet EDTA agglutination
改用citrate

MDS plt沒有granule會不準確
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NTUH每天6000個CBC 常規35項
1200要做WBC differential
300機器會自動染色觀看
60個需要人工染色

NTUH是大宗的
所以NHI打七折給付


Positive: 異常
  • count
  • differential
  • morphology
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Chédiak–Higashi syndrome[1] is a rare autosomal recessive disorder that arises from a mutation of a lysosomal trafficking regulator protein,[2] which leads to a decrease in phagocytosis. The decrease in phagocytosis results in recurrent pyogenic infections, partial albinism and peripheral neuropathy. It occurs in humans, cattle, blue Persian cats, Australian blue rats,[3] mice,[4] mink,[4] foxes,[4] and the only known captive albino orca.[5]


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[醫如往常] Senior Clerkship Day 92: Lab Medicine: Hepatology Clinical Chemistry Instrument

Clinical Chemistry Instrument
鄭醫師
Spectrophotometry
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Chemistry
Tungsten 350-800nm
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Endogenous interference

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Flow cytometry
Laser
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Monochromator

Diffraction gratings

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Cuvets
Sample holder
Quartz, plastics, borosilicated glass
乾淨的水
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Detector
Photodiode array

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Beer's law


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Indicator
Chromophores
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Glucose hexokinase method
NAD→NADH

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化學標準化
1U = Catalyze 1 umole substrate in 1 minute
37℃

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Immunoassay 沒有標準化
因為各家抗體不一樣

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High dose hook effect
Lattice precipitation

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Pancreas cancer cyst change
Pancreatitis

幾十萬測出來只有幾千

先dilute 再做就會準了
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Turbidimetry
可以直接在生化儀上做
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Light scatter
Nephelometry


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太大太小的東西不能測


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Labeled method
  • Radioactive 準確度高
  • Fluorescence
  • Luminescence 藍色為主， 干擾少
  • Enzyme 便宜， 干擾多
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競爭性的是雙曲線， 因此只有中間準

非競爭型正關係比較準

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Heterogeneous assay
ELISA
  • 大小分子都可以驗
  • 敏感性高
  • 不過相對不精密
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化學冷凝光

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Evening 洪醫師
異常值一小時 危急值半小時


移植八項= 針扎十項-AST, ALT
  • Anti-HBVs
  • HBV Surface antigen
  • Anti-HBVcore
  • Anti-HCV
  • HIV ag/ab
  • Syphilis VDRL/RPR,  FTA-ABS/ TP-PA

前兩項HBV不會緊急通報
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CSF五項antigen
  1. Streptococcus pneumoniae
  2. Streptococcus group B ?
  3. HiB; Haemophilus influenzae type B
  4. Mycobacterium tuberculosis
  5. Escherichia coli (carrying the K1 antigen).
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流感快篩
  • -
  • A
  • B
  • A+B (可能是干擾)
  • 無法判定
共五種結果
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[醫如往常] Senior Clerkship Day 91: Lab Medicine: Diagnostic Hepatology

Hepatology 陳醫師

data異常一定要去看病人
Hyperglycemia-> 可能是從D5W IV側抽血造成的
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AST
  • 80% mitochondria
  • Half-life 17 hrs
  • Acute >10x

ALT
  • Chronic
  • Half-life 47 hrs
  • Acute >10x
    • Viral (>2000IU is very dangerous)
      • Jaundice 70% HAV(good prognosis), 35%HBV, 25%HCV
      • Mild fever通常是HAV，糞便要用lysol消毒，vaccination兩劑撐廿年，incubation 1mo，症狀出現之前糞便就有病毒
      • HBV分八種genotype，華人常見BC, C outcome很差，不過genotype在biofunction沒有甚麼實際差異。疫苗要>10IU/ml才有保護力。Anti-Hbe spontaneous seroconversion 10-20% annually. Adult得的<5% 變carrier
HBsAg
HBsAb
HBeAg
HBcAb
HBV DNA
Acute
+
-
+
IgM
+
Clerared infection
-
+
-
IgG
-
vaccinated
-
+
-
-
-
Inactivated carrier
+
-
-
IgG
<2000IU/ml
Chronic infection with active replication
+
-
+/-
IgG
>2000IU/ml
  • HCV 80%會變成carrier, asymptomatic,
  • HEV: High risk for pregnancy->fulminant hepatic failure. Window period 6-8 weeks.
  • Ischemia
  • Toxin/drug (3000IU是正常的，排除underlying就OK) Ex: statin (2.5% population)
  • Autoimmune
    • Type 1
      • ANA (Cytoplasmic); anti nuclear antibody
      • ASMA; anti smooth muscle antibody
      • AAA; anti actin antibody
    • Type 2
      • ALKM1; anti liver kidney microsomal I antibody
      • ALCM; anti liver cytosol 1 antibody
Ref.周貝倫 自體免疫性肝炎 - Taiwan Society of Internal Medicine http://www.tsim.org.tw/journal/jour20-3/03.PDF

  • Early phase of obstruction (jaundice & pain)
    • PBC; Primary Biliary Cirrhosis: AMA
    • PSC; Primary Sclerosing Cholangitis
    • Gallstones, CBD stones, pancreatic cancers
  • AST/ALT 3-5X
    • NASH; non-alcoholic steatohepatitis
      • 不一定fat有關，可能跟biofilm有關
      • 可能變成HCC
      • Asymptomatic
  • Gilbert syndrome
    • 2-10% population
    • Unconjugated bilirubin levels fluctuate
    • No risk of kernicterus to the fetus (不用浪費錢驗bilirubin)
    • R/o hemolysis
  • Wilson's disease
    • Low Ceruloplasmin (homozygous 65-95%, heterozygous 20%)

Factors
  • BMI
  • Exercise: Independent AST↑
  • Hemolysis: AST↑ ALT↑ Red urine, Occult blood, pale face, dizziness
  • Rhabdomyolysis: AST↑ ALT↑ Red urine, Occult blood(-), pale face(-)
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Gamma GT
  • Confirm ALP↑ due to hepatic source
  • Alcohol
  • Drugs: statin
  • BMI
  • steatohepatitis (一般視為正常人)

ALP
  • Liver and bone
  • BMI, pregnancy
  • Marker of cholestasis
  • Half-life 1 week
  • 可以用ALP isoenzyme (很貴), 5-NT, gamma GT 驗證

Conjugation Bilirubin
  • Exercise
  • Hemolysis
  • Hemolytic anemia

INR

Thrombocytopenia
  • Liver fibrosis

Albumin
  • Half-life 19-21 days
  • Nephrotic syndrome
  • Burns
  • Enteropathy
  • SIRS
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ALP
AST
ALT
 GGT
 T-bil
TP
Albumin
Hepatocellular pattern
-
↑
↑
-



Cholestatic pattern
↑
-
-
↑



Mixed pattern
↑
↑
↑
↑



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對於無症狀的人，做預防醫學
抽Anti-Hbs IgG, anti-HCV, Anti-HAV IgG
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對於 RUQ pain, jaundice, fever, AST/ALT>1000 U/L
抽Anti-Hbc IgM, HbsAg, Anti-HAV IgM, anti-HCV (rare acute onset)
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