Case Studies

Received 3.6.05 | Revisions Received 3.16.05 | Accepted 3.17.05

Neck Pain and Rash in an 18-Year-Old Student

Monte Willis, MD, PhD, Michael Roth, MD, Peter Gilligan, PhD
(Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, NC)

Downloaded from https://academic.oup.com/labmed/article-abstract/36/7/419/2657419 by guest on 17 January 2020

DOI: 10.1309/YWACB7N08JJ2KWD6

Patient Past Medical History tachycardia, hypotension, and purpuric lesions

18-year-old Caucasian college student.
Chief Complaint
Headache and skin rash.
History of Present Illness
The patient reported having a sore throat within
the past week. One day prior to admission, he
experienced nausea and vomiting. On the day
of admission, while attending class, he noticed
“spots” on his arms, legs, trunk, and abdomen.
Shortly before his presentation to the
emergency department, he developed fatigue,
headache, neck pain, and photophobia.
The patient had no history of abdominal pain,
tick bites, sick contacts, sexually transmitted
diseases, or recent travel. The patient received
quadravalent Neisseria meningitidis vaccination
at the County Health Department 6 months
prior to his admission.
Family History
Non-contributory.
Physical Exam
Vital signs: temperature, 36.8°C; heart rate,
114 beats per minute; respiratory rate, 24 per
minute; blood pressure, 88/34 mm Hg.
Pertinent physical exam findings included
on his arms, legs, trunk, and genitals (Image 1).
He was acutely ill in appearance, but oriented
with nuchal rigidity on neurologic exam (positive
Brudzynski and Kernig signs).
Principal Laboratory Findings
At presentation (Table 1).
Results of Additional Diagnostic
Procedures
An echocardiography revealed mild left
ventricular enlargement with decreased
function [estimated ejection fraction = 30%
(Normal >60%)]. A chest x-ray demonstrated
pulmonary edema.

Questions: and 3) disorders of coagulation (eg, von Willebrand’s disease,

1. What are this patient’s most striking clinical and laboratory
findings?
2. How do you explain this patient’s most striking clinical and
laboratory findings?
3. What condition(s) is (are) suggested by this patient’s most
striking clinical and laboratory findings?
4. What additional test(s) should be ordered on this patient
and why?
5. What is this patient’s most likely diagnosis?
6. How is this patient’s condition typically treated?
Possible Answers:
1. Clinically, the most striking findings in this patient are
purpuric skin lesions located on his legs, arms, trunk, and genitals;
tachycardia; hypotension; and nuchal rigidity. Significant labora-
tory findings include normocytic anemia, thrombocytopenia, pro-
longed PT and PTT, elevated D-dimer, decreased fibrinogen and
ATIII activity, elevated creatinine, decreased calcium, magnesium,
phosphorus, and an elevated AST and ALT (Table 1).
2. Purpura represents bleeding into the skin and mucosal
membranes resulting in a dark (purple) non-blanching rash
that may be caused by a variety of conditions. Generally pur-
pura may be categorized by 3 major etiologies: 1) vascular dis-
orders (eg, viral illnesses, sepsis); 2) abnormalities in platelet
number and function (eg, infections, autoimmune diseases);
proteins C, S, antithrombin III deficiencies).1 Nuchal rigidity is
the inability of a patient to place their chin to their chest pas-
sively without involuntary muscles spasms preventing it. This
represents inflammation of the meninges, the delicate
membranes that cover the brain, and is often the result of an
infectious agent. Normocytic anemia, or the decrease in normal
sized red cells, may be associated with several diseases such as
chronic inflammation (infection, connective tissue disease),
chronic renal failure, endocrine failure, hepatic disease, or blood
loss. Significantly decreased platelets (thrombocytopenia) can be
caused by: 1) decreased platelet production; 2) splenic sequestra-
tion, hypersplenism; and 3) increased platelet destruction. De-
creased production may be seen in processes that affect the bone
marrow directly such as leukemia, viral infections, and radiation.
Increased platelet destruction can be non-immune or immune
mediated. Non-immune mediated destruction is seen in dissemi-
nated intravascular coagulation (DIC) and thrombotic thrombo-
cytopenia (TTP), while immune mediated destruction is seen in
alloimmune thrombocytopenia, post-transfusion purpura, and
idiopathic thrombocytopenic purpura (ITP).1 A prolonged PT
and PTT suggests that an excessive activation of the coagulation
cascade has occurred, resulting in the formation of fibrin. This
activation of the coagulation cascade is further evidenced by the
decreased fibrinogen, which is used to make a fibrin matrix for
clotting. Factors that prevent coagulation (specifically anti-
thrombin III) are decreased in this patient. When D-dimer, a
degradation product of fibrin, is elevated, fibrinolysis is occur-
ring. A prolonged PT and PTT, decreased fibrinogen and anti-
thrombin III, and an elevated D-dimer in the context of this

labmedicine.com July 2005 䊏 Volume 36 Number 7 䊏 LABMEDICINE 419

Case Studies
Image 1_The patient’s skin lesions during the first 24 hours after admission to the hospital. The distribution of the rash was over his entire body.
patient’s history is highly consistent with DIC. Moreover, DIC
leads to purpura fulminans, thrombocytopenia, and normocytic
anemia described above and can result from bacterial
sepsis/meningitis.
Creatinine is continuously released from muscle and cleared
by renal excretion. Its elevation can be an indicator of decreased
renal function. Decreased circulating calcium may be associated
with decreased PTH secretion or with hyperphosphatemia lead-
ing to calcium precipitation. Decreased circulating magnesium is
generally associated with a decreased intake, an increased loss due
to renal magnesium wasting, and acute myocardial infarction.2
Decreased phosphorous can be due to inadequate intestinal phos-
phate absortion, excessive kidney excretion, or the shift of phos-
phorous from extracellular to intracellular compartments.3
420 LABMEDICINE 䊏 Volume 36 Number 7 䊏 July 2005
Downloaded from https://academic.oup.com/labmed/article-abstract/36/7/419/2657419 by guest on 17 January 2020
Hypocalcemia is commonly associated with critically ill patients
and correlates with the severity of illness.4,5 Decreased magne-
sium has also been associated with sepsis.6 Decreased phospho-
rous levels are associated with malnutrition, refeeding syndrome,3
sepsis, trauma, diuretics, and steroid therapy.7,8 The transami-
nases aspartate aminotransferase (AST) and alanine aminotrans-
ferase (ALT) are sensitive indicators of liver injury and are used to
detect diseases such as hepatitis. Alanine aminotransferase is
found mainly in the liver, while AST can be found in the liver as
well as muscle, organs, and erythrocytes. Acute elevations of AST
and ALT, such as those seen in this case, are seen in disorders
with extensive hepatocellular injury such as viral hepatitis,
ischemic liver injury (eg, severe cardiac dysfunction, shock, sep-
sis), or drug/toxin mediated liver injury.
labmedicine.com
 Case Studies

Table 1_Principal Laboratory Findings

Test Patient’s Result “Normal”

Reference Interval

Hematology
WBC Count 5.4 4.5-11.0 x109/L
28.4 (24 hours)
46.7 (48 hours)
RBC 3.51 4.50-5.90 x1012/L
Hgb 11.6
Hct 33.0 41.0-53.0%
MCV 94 80-100 fL
Platelets 87 150-440 x109/L
67 (24 hours)

Downloaded from https://academic.oup.com/labmed/article-abstract/36/7/419/2657419 by guest on 17 January 2020

46 (48 hours)
Chemistry
Sodium 136 135-145 mmol/L Image 2_Gram stain of a representative CSF with multiple intracellu-
Potassium 4.1 3.5-5.0 mmol/L lar gram-negative diplococci (arrows) in neutrophils identified as
Chloride 104 98-107 mmol/L Neisseria meningitidis. 1,000x magnifcation.
CO2 22 22-30 mmol/L
BUN 19 7-21 mg/dL
36 (24 hours)
Creatinine 2.7 0.8-1.4 mg/dL 4. The early recognition of acute infections of the nervous
Calcium 7.0 8.5-10.2 mg/dL system is necessary to initiate antimicrobial therapy quickly, which
Magnesium 1.0 1.6-2.2 mg/dL
Phosphorus 1.4 2.4-4.5 mg/dL can be lifesaving. Therefore, the identification of the offending
AST 51 15-45 U/L organism is most important. In this patient, blood culture should
673 (24 hours) be performed in order to isolate an infectious cause of this
ALT 48 patient’s possible meningitis and shock (Image 2). Since the pa-
484 (24 hours) 10-40 U/L tient was in DIC, a lumbar puncture for CSF was not performed
ALP 126 65-260 U/L
GGT 45 13-68 U/L because of the high risk of bleeding. Aerobic blood cultures turned
CK 181 70-185 U/L positive within 24 hours and gram-negative diplococci were iden-
CK-MB 1.2 0.0-6.0 ng/ml tified on a Gram stain smear of the blood cultures. The blood cul-
Lactate Dehydrogenase 874 340-670 U/L tures were plated on chocolate blood agar at 35°C in 5% CO2.
Troponin T <0.029 0.000-0.029 ng/ml The organisms were found to be oxidase-positive and had the abil-
PTT 84.1 22.6-32.4
PT 20 11-14 ity to utilize maltose and glucose. The culture was sent to the State
INR 1.8 of North Carolina Public Health Laboratory, as required by law,
D-dimer 23.4 0.0-0.5 where serogrouping was performed.
Fibrinogen 107 150-504
ATII Activity 59 70-118 5. Most likely diagnosis: Neisseria meningitidis bacteremia
WBC, white blood cell; RBC, red blood cells; HCT, hematocrit; MCV, mean corpuscular volume; and meningitis.
BUN, blood urea nitrogen; AST, aspartate aminotransferase; ALT, alanine aminotransferase; In the United States, sporadic Neisseria meningitidis meningo-
ALP, alkaline phosphatase; GGT, gamma-glutamyl transferase; CK, creatine kinase. coccal disease presents in approximately 1/100,000 people per
year.10 There are 2 peak ages of infection: infants 3 to 9 months
of age in whom protective antibodies have not yet formed (10 to
15 cases/100,000 infants/year) and teenagers subjected to
3. In patients with clinical findings suggestive of menin- crowded conditions such as dormitories and barracks (<1
gitis (fever, headache, nuchal rigidity), the differential diagno- case/100,000 people/year).10 The patient in the present case is a
sis should include bacterial meningitis, viral meningitis, college student living in a dormitory. The highest incidence of
encephalitis, focal infections (brain abscess and subdural disease occurs during the winter months when respiratory viral
empyema), and infectious thrombophlebitis. Fever, headache, illnesses are at their peak.
and nuchal rigidity occur in >90% of meningitis cases along Neisseria meningitidis (meningococcus) is subdivided or
with mental status changes in >75%. Each of these infections grouped based on the antigenic structure of the capsular polysac-
can start with a fever and headache in a previously healthy charides (A, B, C, Y, W-135). Meningococci colonize the upper
individual.9 In community-acquired bacterial meningitis in respiratory tract of about 10% of healthy individuals.11 Infection
adults, Streptococcus pneumoniae (51%), Neisseria meningitidis occurs by either direct contact or by respiratory droplets.
(37%), Listeria monocytogenes (4%) are the most common eti- Meningococci are internalized by non-ciliated mucosal cells
ologies.9 Profound alterations in consciousness are less com- and/or cross them to enter the submucosa and the blood stream.
mon in viral meningitis than that seen in bacterial meningitis. However, it is not essential that the organisms infect the blood
Meningitis is unique from other brain infections such as en- for survival.10 The virulence traits of meningococcus include an
cephalitis, focal infections, and infectious thrombophlebitis, anti-phagocytic capsule and outer membrane proteins such as
which largely result in focal neurological deficits. The patient LOS (lipo-oligosaccharide or endotoxin) and pili to facilitate
in this case had symptoms consistent with meningitis (nuchal adhesion.10 Multiple host factors play a role in keeping N.
rigidity, headache, mental status changes) in addition to evi- meningitidis at bay in the nasopharynx. To prevent growth, anti-
dence of bacteremia that possibly initiated the diffuse intravas- bodies with bactericidal activity are needed, in addition to op-
cular coagulation and skin purpura. sonic antibodies and phagocytes. These antibodies are serogroup

labmedicine.com July 2005 䊏 Volume 36 Number 7 䊏 LABMEDICINE 421

Case Studies
Figure 1_Pathophysiology of meninococcemia infection. These mecha-
nisms explain the major sequelae seen clinically: 1) capillary leak, 2)
intravascular thrombosis, 3) cardiac dysfunction, 4) multi-organ failure
due to impaired perfusion. LOS=Lipo-oligosaccharide; LBP=LPS bind-
ing protein. Based on: Pathan, et al, 2003 and Stephens et al, 2005.
specific, usually of IgG or IgM, and generally bind the capsular
surface.10 Genetic associations with host determinants of
meningococcus infection have been made with multiple genes
involved in the innate immune system.12 Meningococcus infec-
tion is a complex interaction between bacterial virulence factors
and genetically determined host responses.
If N. meningitidis is able to enter the blood stream from the
upper respiratory tract, replication occurs either slowly or rap-
idly. Slow growth allows the bacteria to seed in sites such as the
meninges, joints, and pericardium. Rapid proliferation is associ-
ated with meningococemia resulting in petechiae, purpura, DIC,
and shock. When meningococci enter the blood, 2 main diseases
result: 1) meningitis; 2) fulminant meningococcemia (purpura
fulminans). In people who develop blood stream invasion, ap-
proximately 55% will experience meningitis alone,
approximately 30% will have meningitis and meningococemia,
and approximately 15% will have only fulminant meningococ-
cemia (without meningitis). Based on this patient’s clinical signs
and symptoms, he had meningitis (headache, nuchal rigidity)
and bacteremia (hypotension, tachycardia, purpuric rash). Based
on his clinical presentation and laboratory findings of thrombo-
cytopenia, DIC, elevated AST/ALT, and identification of
meningococcus in the blood, the most likely diagnosis is fulmi-
nant meningococcemia/meningitis.
Neisseria meningitidis infection results in the most rapid form
of septic shock and differs from other organisms by the promi-
nence of hemorrhagic skin lesions and the consistent develop-
ment of DIC. The dominant pro-inflammatory molecule that
mediates meningococcal disease is its endotoxin (specifically its
lipid A moiety). The outer membrane of meningococci contains
lipo-oligosaccharide (LOS) that is loosely connected to the un-
derlying peptidoglycan.10 The loosely connected LOS accounts
for its shedding as the bacteria grow at a much faster rate than
other gram-negative bacteria. The active component in LOS,
however, is identical to that of lipopolysaccharide (LPS) found in
other gram-negative bacteria. The detectable plasma endotoxin is
10 to 1,000-fold greater in patients with meningococcal
bacteremia than other gram-negative bacteria and may account
422 LABMEDICINE 䊏 Volume 36 Number 7 䊏 July 2005
for the more fulminant disease that meningococcus causes com-
pared to sepsis caused by other gram-negative bacteria.10
The major pathways of meningococcus pathogenesis are
outlined in Figure 1. Endotoxin is released from meningococci
and activates the immune system by 3 major pathways. First,
LOS interacts with toll-like 4 (Tlr-4) receptors on monocytes,
neutrophils, and endothelial cells releasing cytokines and other
mediators.13 Meningococci also invade endothelial cells directly
producing pro-inflammatory molecules as well as upregulating
adhesion molecules for leukocytes.13 The main pro-inflamma-
tory mediators that have been identified include TNF-α, IL-1β,
IFN-γ, and IL-8.13 The second major pathway involves the co-
agulation system. Pro-coagulant and anti-fibrinolytic
Downloaded from https://academic.oup.com/labmed/article-abstract/36/7/419/2657419 by guest on 17 January 2020
mechanisms are activated in meningococcemia, resulting in the
tendency for fibrin deposition and thrombosis.13 Upon activa-
tion by LOS, monocytes synthesize tissue factor in addition to
pro-inflammatory cytokines. This uncontrolled activation of the
coagulation cascade results in clotting and deficiencies in regula-
tors of the cascade: protein S, protein C, and anti-thrombin
III.13 Moreover, fibrin deposition is favored by the anti-coagu-
lant tendency from the excessive plasminogen activator
inhibitor-1 (PAI-1) released from endothelial cells and
platelets.13 Plasminogen activator inhibitor-1 inhibits the forma-
tion of plasmin and the degradation of clotting. Bilateral acute
adrenal gland hemorrhage can result in adrenal insufficiency in
meningococci infection. This clinical scenario is referred to as
the Waterhouse-Friderichsen syndrome and is rare. More com-
monly, partial adrenal insufficiency results and the patient is un-
able to mount a normal hypercortisolemic response to stress,
increasing the risk of mortality and morbidity.14 The third major
pathway in the pathogenesis of meningococcus involves the acti-
vation of classical complement pathway by antibodies and/or
mannan binding lectin or by the alternative complement path-
way, which leads to endothelial cell damage. These mechanisms
explain the capillary leak (hypotension), intravascular thrombo-
sis, cardiac dysfunction, and multi-organ failure that may be
seen in meningococcal infections.
6. Patients with meningococcemia should be treated with a
third-generation cephalosporin (eg, cefotaxime or ceftriaxone).
The third-generation cephalosporin should be combined with
agents to cover bacteria that can cause similar symptoms (eg, S.
pneumoniae and H. influenzae) until the etiologic agent can be
identified. Penicillin G remains an acceptable alternative for con-
firmed meningococcal disease. However, it should be noted that
an increased prevalence of meningococci with reduced penicillin
susceptibility has been reported.15 Upon admission the patient
was treated empirically for meningitis with ceftriaxone,
vancomycin, and doxycycline. Upon identification of meningo-
coccemia, the vancomycin and doxycycline were discontinued.
Meningococcal disease is associated with a high morbidity
and mortality.16 Approximately 500,000 cases occur worldwide,
of which approximately 10% result in death.17,18 Of the patients
that survive, deafness, seizures, amputation, and mental retarda-
tion can result.19-22
Vaccination. Eighty to ninety percent of immunocompetent
adults vaccinated with quadravalent meningococcal polysaccha-
ride vaccine against serotypes A, C, W-135, and Y develop pro-
tective immunity. Children >3 years of age may be vaccinated
with multiple doses to prevent serogroup A infection. The dura-
tion of the adult immunity is estimated to be less than 5 years.10
There is currently no vaccine for serogroup B because its poly-
saccharide is not sufficiently immunogenic.10 While the patient
labmedicine.com

described in this case study DID receive a meningococcal vaccine
within the past 6 months, it was not protective because he was
infected with serogroup B meningococcus as determined by the
North Carolina State Public Health Laboratory.
Chemoprophylaxis. Since the attack rate for household
contacts is >400 fold more than the general population, close
contacts should be treated with prophylactic antimicrobials.
Ciprofloxicin is the most frequently used agent. Rifampin may
be used in children but it should be noted that rifampin resistant
meningococcal isolates have been reported.23
Patient follow-up. Over the first 4 days of the patient’s hos-
pitalization, normalization of his PT/PTT, LFTs, creatinine, and
thrombocytopenia occurred. Clinically his mental status returned
to normal as well. Adrenal insufficiency was ruled out as the pa-
tient underwent a low- and high-dose co-syntropin stimulation
test, to which the cortisol response was appropriately increased.
Since the patient was at increased risk for seizures after his
meningococcemia, an EEG was performed and his risk for
seizures was thought to be low. The patient’s purpura fulminans
was treated symptomatically and was beginning to resolve by the
time the patient was discharged on day 11. The leading cause of
morbidity and mortality in sepsis is the myocardial depression,
which generally lasts 7 to 10 days and has been shown to be me-
diated by the pro-inflammatory cytokines released in response to
LPS such as TNF-α, IL-β, and IFN-γ.24 On day 2, the patient
had an estimated cardiac output (ejection fraction) of 30% (nor-
mal >60%). By day 11, his cardiac function was still impaired,
although improved (45%). While he was well enough to be dis-
charged, he was still experiencing significant cardiac dysfunction
that would eventually return to normal. The patient was treated
as a heart failure patient until another echo could be performed
in 4 to 6 weeks. Lastly, a complement panel looking for deficits
for the terminal complement components was performed and
found to be normal. People with these deficiencies are more
prone to infections with meningococcus. LM
Keywords
Neisseria meningitidis, meningococcus, lipo-oligosaccharide,
endotoxin, cytokines, DIC, toll-like receptor 4, vaccination
1. Gurevitch AW, Zipperstein K. Dermatologic problems in the intensive care
unit. In: Bongard FS, ed. Current Critical Care Diagnosis & Treatment. 2nd ed.
New York: The McGraw-Hill Companies, Inc; 2003.
2. Bongard FS, Sue DY. Fluids, electrolytes, & acid-base. In: Bongard FS, ed.
Current Critical Care Diagnosis & Treatment. 2nd ed. New York: The McGraw-
Hill Companies, Inc; 2003.
labmedicine.com
Case Studies
3. Schade Willis T, Boswell R, Willis MS. Refeeding syndrome in a severely
malnourished child. Lab Med. 2004;35:548-552.
4. Gauthier B, Trachtman H, Di Carmine F, et al. Hypocalcemia and
hypercalcitoninemia in critically ill children. Crit Care Med. 1990;18:1215-
1219.
5. Zivin JR, Gooley T, Zager RA, et al. Hypocalcemia: A pervasive metabolic
abnormality in the critically ill. Am J Kidney Dis. 2001;37:689-698.
6. Lote K, Andersen K. Hypocalcemia and hypomagnesemia in meningococcal
septicemia. Tidsskr Nor Laegeforen. 1977;97:1667-1669.
7. Menezes FS, Leite HP, Fernandez J, et al. Hypophosphatemia in critically ill
children. Rev Hosp Clin Fac Med Sao Paulo. 2004;59:306-311.
8. Antachopoulos C, Papassotiriou I. Hypophosphatemia in meningococcal
sepsis. Pediatr Nephrol. 2004.
9. van de Beek D, de Gans J, Spanjaard L, et al. Clinical features and prognostic
Downloaded from https://academic.oup.com/labmed/article-abstract/36/7/419/2657419 by guest on 17 January 2020
factors in adults with bacterial meningitis. N Engl J Med. 2004;351:1849-
1859.
10. Stephens DS, Munford RS, Wetzler LM. Meningococcal infections. In: Kasper
DL, Braunwald E, Fauci AS, et al, eds. Harrison's Principles of Internal
Medicine. 16th ed. New York: McGraw-Hill Companies, Inc.; 2005.
11. Yazdankhah SP, Caugant DA. Neisseria meningitidis: An overview of the
carriage state. J Med Microbiol. 2004;53:821-832.
12. Emonts M, Hazelzet JA, de Groot R, et al. Host genetic determinants of
Neisseria meningitidis infections. Lancet Infect Dis. 2003;3:565-577.
13. Pathan N, Faust SN, Levin M. Pathophysiology of meningococcal meningitis
and septicaemia. Arch Dis Child. 2003;88:601-607.
14. Bosworth DC. Reversible adrenocorticol insufficiency in fulminant
meningococcemia. Arch Intern Med. 1979;139:823-824.
15. Antignac A, Ducos-Galand M, Guiyoule A, et al. Neisseria meningitidis strains
isolated from invasive infections in France (1999-2002): Phenotypes and
antibiotic susceptibility patterns. Clin Infect Dis. 2003;37:912-920.
16. Thorburn K, Baines P, Thomson A, et al. Mortality in severe meningococcal
disease. Arch Dis Child. 2001;85:382-385.
17. Tikhomirov E, Santamaria M, Esteves K. Meningococcal disease: Public health
burden and control. World Health Stat Q. 1997;50:170-177.
18. Balmer P, Miller E. Meningococcal disease: How to prevent and how to
manage. Curr Opin Infect Dis. 2002;15:275-281.
19. Offit PA, Peter G. The meningococcal vaccine-public policy and individual
choices. N Engl J Med. 2003;349:2353-2356.
20. Pollard AJ, Levin M. Vaccines for prevention of meningococcal disease. Pediatr
Infect Dis J. 2000;19:333-345.
21. Kirsch EA, Barton RP, Kitchen L, et al. Pathophysiology, treatment and
outcome of meningococcemia: a review and recent experience. Pediatr Infect
Dis J. 1996;15:967-979.
22. Tzeng YL, Stephens DS. Epidemiology and pathogenesis of Neisseria
meningitidis. Microbes Infect. 2000;2:687-700.
23. Nolte O, Muller M, Reitz S, et al. Description of new mutations in the rpoB
gene in rifampicin-resistant Neisseria meningitidis selected in vitro in a stepwise
manner. J Med Microbiol. 2003;52:1077-1081.
24. Court O, Kumar A, Parrillo JE. Clinical review: Myocardial depression in
sepsis and septic shock. Crit Care. 2002;6:500-508.
July 2005 䊏 Volume 36 Number 7 䊏 LABMEDICINE 423