ࡱ > v bjbjVV < < 6~ = N
N
4 h d l PN R d @ B M M M M M M M O R M % % % M
N X- X- X- % 8 G N X- % M X- X- 6 E
G h! ( F G N 0 PN F S ) | S 8
G S
G % ! & X- " # % % % M M $- 4 % % % PN % % % % S % % % % % % % % % N
\ : Additional file 1, Table S1.
Title: Summary of 20 patients with T. whipplei chronic encephalitis.
Description: The characteristics of our 5 patients with T. whipplei encephalitis and 15 patients from the literature are summarised in this Table.
Patients
[Respective references]Sex/
Age (y)Neurological signsExtraneurological signs Specific diagnosisPretreatment examinationsTreatmentFollow-upCERTAIN DIAGNOSIS OF T. WHIPPLEI ENCEPHALITISDiagnosis based on T. whipplei PCR of CSF and/or brain biopsy1 Patient 1M/39First symptoms: Dysarthria
Symptoms: Dysarthria, cognitive impairment (dementia), choreiform movements, apathy, depression and intermittent diplopiaPrevious: 3 years before, unexplained diarrhoea for 3 weeks, cytolytic hepatitis, weight gain
Contemporary: Dysphagia, cytolytic hepatitis, weight gainBrain biopsy:
Astrocytar gliosis and neoangiogenesis
PAS -, IHC -, regular PCR: -, repeat PCR +
First CSF:
Regular PCR: - Repeat PCR: +
Second CSF:
Regular PCR: -
Repeat PCR: +
Gastric and SB biopsy:
PAS -, IHC -, PCR -
Saliva: PCR -
Stools: PCR -SGPT = 123 UI/L and SGOT = 51 UI/L.
CSF: 4 g/l of protein, glucose level normal, no cells
Brain CT scan: Somewhat diminished density involving the right lenticuloinsular area and diminished density of the right frontal convexity
Brain MRI: Several high-signal lesions (T2) with a heterogenous contrast (T1) in the cerebral trunk, the anterior hypothalamus, the anterior limbs of the internal capsules and the right centrum semi-ovale.Doxycycline
200 mg
and
hydroxy-chloroquine
200 mg 3 times/day,
and
TMP-SMX
320-1,600 mg/day 3 times/day
for
18 monthsQuick improvement.
Relapse one year after the end of the treatment.
New treatment for 52 months.
Quick improvement.
No sequelae.1 Patient 2M/35First symptoms: Dysuria and hypothalamic signs (impotence)
Symptoms: Gait ataxia, vertiginous sensation and pyramidal syndromePrevious: Asthenia
Contemporary: AstheniaFirst CSF:
Regular PCR: - Repeat PCR: +
Second CSF:
Regular PCR: -
Repeat PCR: +
Gastric and SB biopsy:
PAS -, IHC -, PCR -
Saliva:
Regular PCR: - Repeat PCR: +
Stools:
Regular PCR: - Repeat PCR: +CSF: 2 g/l of protein, glucose level normal, 9 white blood cells/mm3.
Brain MRI: High-signal lesions (T2) in the centrum ovale, particularly in the periventricular area on the left; one of the same type of lesion was observed in the left cerebellar area. A lesion that increased after gadolinium injection was present in the left parieto-occipital area in the white matter.Doxycycline
200 mg
and
hydroxy-chloroquine
200 mg 3 times/day,
and
TMP-SMX
320-1,600 mg/day 3 times/day
for
18 monthsQuick improvement.
No sequelae.
Four years of follow-up.1 Patient 3M/52First symptoms: Cerebellar form (dysarthria and gait ataxia), cognitive impairment (memory impairment and disorientation), and pyramidal syndromePrevious: Unexplained acute diarrhoea, abdominal pain and fever one month before
Contemporary: Dysphagia, abdominal pain, feverFirst CSF:
Regular PCR: - Repeat PCR: +
Second CSF:
Regular PCR: -
Repeat PCR: +
Gastric and SB biopsy:
PAS -, IHC -, PCR -
Saliva: PCR -
Stools: PCR -SGPT = 107 UI/L and SGOT = 51 UI/L
CSF: 0.79 g/l of protein, glucose level normal, 9 white blood cells/mm3 (80% lymphocytes and 20% mononuclear cells).
Brain-CT scan: Normal
Brain-MRI: NormalDoxycycline
200 mg
and
hydroxy-chloroquine
200 mg 3 times/day,
and
TMP-SMX
320-1,600 mg/day 3 times/day
for
18 monthsQuick improvement
No sequelaes
Relapse one year after the end of the treatment, with a discrete cerebellar syndrome and a weight gain of 12 kg.
New treatment for 12 months.
Quick improvement two months later, with the loss of 7 kg.
No sequelae.1 Patient 4M/53First symptoms: Gait ataxia, cognitive impairment (memory impairment and confusion), central nystagmus, and pyramidal syndromePrevious: Unexplained acute diarrhoea three weeks before
Contemporary: None.First CSF:
Regular PCR: - Repeat PCR: +
Second CSF:
Regular PCR: -
Repeat- PCR: +
Gastric and SB biopsy:
PAS -, IHC -, PCR
Stools: PCR -
Blood: PCR -CSF: 0.44 g/l of protein, glucose level normal, 20 white blood cells/mm3 (mainly lymphocytes).
Brain-MRI: NormalCeftriaxone
2 g/day
and
TMP-STX
320-1,600 mg/day
for 15 monthsSlight improvement.
Few sequelae.
We were not able to continue contact with this patient.1 Patient 5F/33First symptoms: Headache, diplopia and seizure
Symptoms: Cerebellar form (dysarthria and gait ataxia), cognitive impairment (reasoning impairment), choreiform movements, oculomasticatory myorhythmia, right facial paralysis, nystagmus, and muscle weaknessNoneBrain biopsy: PAS -, IHC -, PCR -
CSF: PCR +
Blood: PCR
Gastric and SB biopsy: PAS -, IHC -, PCR
Saliva: PCR
Stools: PCR -CSF: 0.38 g/l of protein, glucose level normal, 22 white blood cells/mm3 (mainly lymphocytes).
Brain MRI: Mass lesion on the head of left caudate nuclei
Ceftriaxone
2 g/day
and
TMP-STX
320-1,600 mg/day
for 18 months;
Doxycycline
200 mg
and
hydroxy-chloroquine
200 mg 3 times/day
and
sulfadiazine
1g/day 3 times/daySlight improvement.
Few sequelae.
Relapse six months after the end of the first treatment.
Slight improvement.
Few sequelae.2 Patient 6
ADDIN REFMGR.CITE Rossi20051170Cerebral Whipple's disease as a cause of reversible dementiaJournal1170Cerebral Whipple's disease as a cause of reversible dementiaRossi,T.Haghighipour,M.Haghighi,M.Paolini,S.Scarpino,O.2005DementiaNot in File258261Clin Neurol Neurosurg107Clin Neurol Neurosurg1[30]F/72First symptoms:
Personality changes (very anxious), apathy, and cognitive impairment (memory impairment and confusion)
Symptoms: Gait ataxia, cognitive impairment (disorientation), extrapyramidal signs, and upper motor neuron disorderPrevious: Weight loss
Contemporary: Weight loss
Serum: PCR +
CSF: PCR +
Duodenum and ileum biopsies: PAS -CSF: 45 white blood cells/mm3, (mainly lymphocytes) and elevated protein content
EEG: Slowing of the background activity and recurrent diffuse synchronous slow and sharp wave discharges.
Brain MRI: Mild cortical and subcortical atrophy, with diffusely distributed lacunary lesions that were hypointense on T1-weighted and hyperintense on T2-weighted images. No enhancement after gadolinium administration.TMP-SMXQuick improvement.
No sequelae.2 Patient 7 ADDIN REFMGR.CITE Lee2002503Whipple disease with supranuclear ophtalmoplegia diagnosed by polymerase chain reaction of cerebrospinal fluid.Journal503Whipple disease with supranuclear ophtalmoplegia diagnosed by polymerase chain reaction of cerebrospinal fluid.Lee,A.G.2002Whipple DiseasePolymerase Chain ReactionCerebrospinal FluidNot in File1821J Neuroophtamol22J Neuroophtamol1Nelson20051283Proton magnetic resonance spectroscopy and diffusion-weighted imaging of central nervous system whipple diseaseJournal1283Proton magnetic resonance spectroscopy and diffusion-weighted imaging of central nervous system whipple diseaseNelson,J.W.White,M.L.Zhang,Y.Moritani,T.2005/5AgedBrainBrain DiseasesCase ReportCentral Nervous System Bacterial InfectionsdiagnosisDiffusion Magnetic Resonance ImaginghistoryHumansIowaMagnetic Resonance ImagingMagnetic Resonance SpectroscopyMalemethodsWeight LossWhipple DiseaseNot in File320322J Comput.Assist.Tomogr.293University of Iowa College of Medicine, Iowa City, IA 52246, USA. jared-nelson@uiowa.eduPM:15891498J Comput.Assist.Tomogr.1[34,37]M/72First symptoms: Dizziness
Symptoms: Cognitive impairment (memory impairment and incoherent speech), ataxia, supranuclear ophthalmoplegia, and hypersomniaPrevious: Anorexia, fatigue
Contemporary: Anorexia, fatigueCSF: PCR +
Duodenal biopsy:
PAS -Brain MRI: Significant T1, T2, and fluid-attenuated inversion recovery signalled abnormalities in the cerebellar vermis, bilateral cerebellar peduncles, and superior and posterolateral medulla as well as bilateral foci enhancement in the cerebellar subcortical white matter.Ceftriaxone and streptomycin, TMP-SMXNo improvement.
Death.2 Patient 8
ADDIN REFMGR.CITE Henning20061352A case of cerebral Whipple's disease initially presenting with isolated focal myoclonusJournal1352A case of cerebral Whipple's disease initially presenting with isolated focal myoclonusHenning,S.Tings,T.Schmidt,H.Tergau,F.Wolf,S.Scholz,K.Knauth,M.Buchner,H.Gold,R.Paulus,W.2006/6AntibioticsForearmGermanyMyoclonustherapyNot in File659661Eur J Neurol136Department of Clinical Neurophysiology, Georg-August University, Gottingen, Germany. henning@medizin.uni-goettingen.dePM:16796592Eur J Neurol1[35]M/44First symptoms:
Focal jerks of the left hand and the forearm
Symptoms: Cognitive impairment, supranuclear ophthalmoplegia and myoclonus of the left arm and shoulder NoneCSF: PCR + from 3 consecutive lumbar punctures
Duodenal biopsy:
PAS -CSF: Pleocytosis (10-36/mm3) and mildly increased CSF protein (0.54-1 g/l).
EEG: Intermittent bilateral frontotemporal theta activity and no epileptiform discharges.
Brain MRI: Bilateral lesions around the parahippocampal gyri, the third ventricle and dorsal pons consistent with limbic encephalitis extending to the upper brainstem.TMP-SMX and ceftriaxone.
Adjuvant immunotherapy with polyvalent immunoglobulinsSlow improvement.2 Patient 9
ADDIN REFMGR.CITE Panegyres20061834Primary Whipple's disease of the brain: characterization of the clinical syndrome and molecular diagnosisJournal1834Primary Whipple's disease of the brain: characterization of the clinical syndrome and molecular diagnosisPanegyres,P.K.Edis,R.Beaman,M.Fallon,M.2006/9abnormalitiesAdultAtrophyAustraliabloodBrainBrain DiseasesCase ReportCentral Nervous System Bacterial InfectionscomplicationsdiagnosisDnaetiologyEyeFemaleHumansMagnetic Resonance ImagingmethodsmicrobiologyMiddle AgedMovementNervous System DiseasesphysiologyPolymerase Chain ReactionResearchsecondarysecretionSeizuresSyndromeWhipple DiseaseNot in File609623QJM.999Neurodegenerative Disorders Research, Suite 33, 146 Mounts Bay Road, Perth WA 6000, Australia. macfarlane4@optusnet.com.auPM:16905752QJM.1[36]M/46First symptoms:
Cognitive impairment (memory impairment)
Symptoms:
Ataxia, cognitive impairment (confusion and memory impairment), supranuclear ophthalmoplegia, seizures, SIADH, and insomniaNoneCSF: PCR+
Duodenal biopsy:
PAS -, PCR -CSF: 464 white blood cells/mm3 (90% polymorphs, 10% lymphocytes) and decreased CSF protein (0.03 g/l) and glucose (1.6 mmol/l).
November 2003 Brain -MRI: Atrophy and gliosis of right hippocampal formation.
March 2004 Brain MRI:
Development of nodular enhancing lesions (right temporal lobe, caudate nuclei, anterior commissure, right globus pallidus, left insula cortex, left hippocampal formation, lenticular striate territory, mesencephalon and perivascular spaces).Meropenem for 2 weeks, TMP-SMX for 13 monthsSlow improvement.
Sequelae.2 Patient 10
ADDIN REFMGR.CITE Peters2002511Cerebral Whipple's disease with a stroke-like presentation and cerebrovascular pathology.Journal511Cerebral Whipple's disease with a stroke-like presentation and cerebrovascular pathology.Peters,G.du Plessis,D.G.Humphrey,P.R.2002Not in File336339J Neurol Neurosurg Psychiatry73J Neurol Neurosurg Psychiatry1[43]F/39First symptoms: Speech disturbance and weakness
Symptoms:
Cognitive impairment (memory impairment), depression, decreased level of conscientiousness, personality change, seizures, supranuclear ophthalmoplegia, left hemiplegia, urinary incontinence, and paresthesiasPrevious: Unexplained acute diarrhoea 10 months before, associated with a petechial rash
Contemporary: FeverBlood sample: PCR +
Brain biopsy: PAS +, EM + and PCR +
Digestive biopsy: PAS -Brain MRI: Bilateral hemispheric high signal on T2-weighted images.TMP-SMXSlow improvement.
Sequelae.Diagnosis based on positive T. whipplei PCR on samples other than CSF and brain biopsy 2 Patient 11
ADDIN REFMGR.CITE Coria2000504Whipple's disease with isolated central nervous system symtomatology diagnosed by molecular identification of Tropheryma whippellii in peripheral blood.Journal504Whipple's disease with isolated central nervous system symtomatology diagnosed by molecular identification of Tropheryma whippellii in peripheral blood.Coria,F.Cuadrado,N.Velasco,C.Jiménez Carmena,J.J.Jiménez,M.I.Mena,F.J.Acebes,J.M.2000Not in File173176Neurologia15Neurologia1[28]
M/65First symptoms: Gait ataxia, supranuclear ophthalmoplegia, hypothalamic signs (daytime somnolence and nocturnal insomnia)
Symptoms: Decreasing level of conscientiousness, hemiparesia, myorhythmia, myoclonus, and upper motor neuron disorder NoneBlood sample:
PCR +
Brain autopsy:
PAS +
Digestive biopsy:
PAS -CSF: Normal.
Brain MRI: Mild to moderate cortical atrophy without focal abnormalities.Penicillin and streptomycin, followed by TMP-SMXQuick
Improvement.
Sudden death due to a mesenteric thrombosis.2 Patient 12
ADDIN REFMGR.CITE Louis1996232Diagnostic guidelines in central nervous system Whipple's disease.Journal232Diagnostic guidelines in central nervous system Whipple's disease.Louis,E.D.Lynch,T.Kaufmann,P.Fahn,S.Odel,J.1996Not in File561568Ann Neurol40Ann Neurol1[27]F/47First symptoms: Oculomasticatory myorhythmia and nystagmus
Symptoms:
Cognitive impairment (memory impairment), cerebellar form (dysarthria and ataxia), hypothalamic signs (insomnia and intermittent hypersomnolence), depression, supranuclear gaze palsy, and upper motor neuron disorderPrevious: Arthritis.
Contemporary: Fever, submandubular lymph node enlargementCSF: PAS -
Duodenal biopsy: PAS -, PCR +CSF: Protein levels from 0.5 to 0.55 g/l, normal glucose level, and 0 to 70 mononuclear cells.
EEG: Mildly generalised slow background.
Brain-CT: Normal.
Brain-MRI: Arnold-Chiari type 1 malformation with no brainstem compression.Ceftriaxone 2g/d for 6 months
TMP-SMX Improvement
Recurrence with TMP-SMX
Sequelaes2 Patient 13
ADDIN REFMGR.CITE Averbuch-Heller1999365Whipple's disease mimicking progressive supranuclear palsy: the diagnostic value of eye movement recording.Journal365Whipple's disease mimicking progressive supranuclear palsy: the diagnostic value of eye movement recording.Averbuch-Heller,LPaulson,GWDaroff,RBLeight,JR1999Not in File532535J Neurol Neurosurg Psychiatry66J Neurol Neurosurg Psychiatry1[31]F/54First symptoms: Blurred vision
Symptoms:
Gait ataxia, supranuclear ophthalmoplegia, myorhythmia, extra-pyramidal signs and upper motor neuron disorderNoneJejunal biopsy:
PAS - and PCR +Brain-MRI: A venous angioma in the left cerebellar hemisphere.TMP-SMX followed by ceftriaxoneSlow improvement
No sequelaesPOSSIBLE DIAGNOSIS OF T. WHIPPLEI ENCEPHALITISDiagnosis based on positive PAS-staining and electron microscopy of brain biopsy2 Patient 14
ADDIN REFMGR.CITE Romanul1977430Whipple's disease confined to the brain: a case studied clinically and pathologically.Journal430Whipple's disease confined to the brain: a case studied clinically and pathologically.Romanul,FCARadvany,JRosales,RK1977Not in File901909J Neurol Neurosurg Psychiatry40J Neurol Neurosurg Psychiatry1[38]M/40First symptoms: Headache and seizures
Symptoms: Cerebellar form (gait ataxia and dysarthria), cognitive impairment (dementia, memory impairment, confusion), decrease level of conscientiousness, urine incontinence, and upper motor neuron disorderNoneBrain necropsy : PAS + and EM +
Digestive biopsy: PAS -CSF: Pleocytosis and occasional level of protein.
-*Death2 Patient 15
ADDIN REFMGR.CITE Wroe1991230Whipple's disease confined to the CNS presenting with multiple intracerebral mass lesions.Journal230Whipple's disease confined to the CNS presenting with multiple intracerebral mass lesions.Wroe,SJPires,MHarding,BYoul,BDShorvon,S1991Not in File989992J Neurol Neurosurg Psychiatry54J Neurol Neurosurg Psychiatry1[39]M/32First symptoms: Headache
Symptoms: Decreasing level of conscientiousness, cognitive impairment (dementia, disorientation, memory impairment), apathy, upper motor neuron disorder, and seven nerve palsyNoneBrain biopsy: PAS + and EM +
Duodenal and jejunal biopsies:
PAS -CSF: Normal excepted oligoclonal bands.
Brain MRI: Large high-signal mass lesions with peripheral ring enhancement after gadolinium injection.Penicillin and streptomycin for 2 weeks, followed by TMP-SMX for 11 monthsSlow improvement. Sequelae.2 Patient 16 ADDIN REFMGR.CITE Halperin1982428Whipple disease of the nervous system.Journal428Whipple disease of the nervous system.Halperin,JJLandis,DMKleinman,GM1982Not in File612617Neurology32Neurology1[32]M/58Symptoms:
Cerebellar form (dysarthria and gait ataxia), cognitive impairment (memory impairment), supranuclear ophthalmoplegia, dizziness, personality change, nystagmus, upper motor neuron disorder, hypothalamic signs (impotence), and paresthesiasPrevious: Arthralgias
Contemporary: Low-grade feverCSF: PAS -
Brain biopsy: PAS + and EM +
Jejunal biopsy:
PAS -CSF: 100 mg/dl of protein, 99 mg/dl of glucose, 9,330 red blood cells and 4 lymphocytes.
Brain CT scan: Round areas of low density without mass effect in the right medial temporal lobe and right pontine tegmentum. After the infusion of intravenous contrast material, these lesions demonstrated increased intensity. There was slight central and cortical atrophy.ChloramphenicolTCNDeath 6 months after diagnosis2 Patient 17 ADDIN REFMGR.CITE Posada20041032Whipple's disease confined to the brain. A clinical case with pathological confirmation at necropsyJournal1032Whipple's disease confined to the brain. A clinical case with pathological confirmation at necropsyPosada,I.J.Ferreiro-Sieiro,A.Lopez-Valdes,E.Cabello,A.Bermejo-Pareja,F.2004/1/16BrainBrain DiseasescomplicationsetiologyFatal OutcomeFemaleHumanMiddle AgedpathologyWhipple DiseaseNot in File196198Rev Neurol38Rev Neurol1[40]F/63First symptoms: Myorhythmia
Symptoms: Cerebellar form (ataxia and dysarthria), cognitive impairment (memory impairment), decreased level of consciousness, supranuclear ophthalmoplegia, myoclonus, hemiparesia, depression, extra-pyramidal signs, and personality changesPrevious: Arthralgia for 10 years
Contemporary: NoneJejunal biopsy:
PAS -, PCR -
Brain necropsy: PAS+ and EM +CSF: Normal.
EEG: Normal.
Brain CT scan: Normal.
Brain MRI: Normal.No antibioticDeath2 Patient 18
ADDIN REFMGR.CITE Adams1987229Whipple's disease confined to the central nervous system.Journal229Whipple's disease confined to the central nervous system.Adams,MRhyner,PADay,JDeArmond,SSmuckler,EA1987Not in File104108Ann Neurol21Ann Neurol1[41]F/63First symptoms: Cognitive impairment (memory impairment), somnolence and ataxia
Symptoms: Cognitive impairment (disorientation), supranuclear ophthalmoplegia, hypothalamic signs (hyperphagia), and upper motor neuron disorderNoneBrain autopsy:
PAS + and EM +
Digestive biopsy:
PAS -CSF: Normal.
Brain MRI: Abnormal high signal intensity in the hypothalamus, uncus, and medial temporal lobes on T2-weighted images. Penicillin, TMP-SMX, rifampin, chloramphenicolDeath2 Patient 19
ADDIN REFMGR.CITE Schwartz1986448Oculomasticatory myorhythmia: a unique movement disorder occuring in Whipple's disease.Journal448Oculomasticatory myorhythmia: a unique movement disorder occuring in Whipple's disease.Schwartz,MASelhorst,JBOchs,ALBeck,RWCampbell,WWHarris,JKWaters,BVelasco,ME1986Not in File677683Ann Neurol20Ann Neurol1[42]F/55First symptoms: Somnolence, cognitive impairment (confusion, and memory impairment)
Symptoms: Cognitive impairment (disorientation), decrease level of conscientiousness, oculomasticatory myorhythmia, and supranuclear ophthalmoplegiaPrevious: Arthralgia
Contemporary: ArthralgiaBrain autopsy:
PAS + and EM +
Duodenal biopsy: PAS -CSF: Normal.
EEG: Diffusely slow with frontal, intermittent, rhythmic delta waves.
Brain RMI: Increased signal density around third ventricle.NoneDeathDiagnosis based exclusively on oculomasticatory myorhythmia that is considered by some authors as pathognomonic of T. whipplei2 Patient 20
ADDIN REFMGR.CITE Louis1996232Diagnostic guidelines in central nervous system Whipple's disease.Journal232Diagnostic guidelines in central nervous system Whipple's disease.Louis,E.D.Lynch,T.Kaufmann,P.Fahn,S.Odel,J.1996Not in File561568Ann Neurol40Ann Neurol1[27]M/54First symptoms:
Cognitive impairment (dementia), supranuclear ophthalmoplegia, extra pyramidal signs
Symptoms: Gait ataxia, cognitive impairment (memory impairment), depression, and oculomasticatory myorhythmiaNoneOculomasticatory myorhythmia
Digestive biopsy:
PAS --TCN 1g/d.
Prior treatment lost to follow-up.No benefit1: Patients were seen and followed by one of the authors (DR) in consultation.
2: Patients were from the literature review.
*: The diagnosis of T. whipplei infection was made after post-mortem examination.
SGPT : Serum glutamate pyruvate transaminases
SGOT : Serum glutamic oxaloacetic transaminases
PAS+: Light microscopy showing PAS-positive macrophages in infected tissues
EM+: Electron microscopy showing Whipple bacilli in infected tissues
PCR TW+: Polymerase chain reaction showing T. whipplei DNA
MRI: Magnetic resonance imaging
TMP-SMX: Trimethoprim-sulfamethoxazole
TCN: Tetracycline
FLAIR: Fluid attenuation inversion recovery
SIADH: Syndrome of inappropriate ADH secretion
PAGE
PAGE 1
PAGE
PAGE 9
$ % A L b c o p Ȼխ{m{cVVHVV h k h 6CJ mH sH h k h CJ mH sH h@ CJ mH sH h k hp 6CJ mH sH h k hp CJ mH sH h h 5CJ mH sH h CJ mH sH h k h@ CJ mH sH h k h@ 5CJ mH sH h 5CJ aJ mH sH h 5CJ aJ mH sH h`, 5CJ aJ mH sH hd 5CJ aJ mH sH hd hd 5CJ aJ mH sH c & 9 R e
p# $If $If $
7S d a$gdp
!
.
7
@ M ' . 4 < A P T _ c !
,
6 ? z " ͯͯ h k h@ 5h k h@ #h k h@ 5CJ OJ QJ mH sH h k h@ H*mH sH h k h@ mH sH h k h@ 56mH sH h k h@ CJ mH sH h k h@ 5mH sH : G A $If kd $$If F ִ 9!06<