Hyperacute rejection is caused by

1
Hyperacute rejection is caused by A. Preformed
antibodies B. B-cellgenerated antidonor
antibodies C. T-cellmediated allorejection
D. Nonimmune mechanism
2
Answer A. Explanation Hyperacute rejection,
which usually occurs within minutes after the
transplanted organ is reperfused, is due to the
presence of preformed antibodies in the
recipient, antibodies that are specific to the
donor. These antibodies may be directed against
the donor's HLA antigens or they may be anti-ABO
blood group antibodies. Either way, they bind to
the vascular endothelium in the graft and
activate the complement cascade, leading to
platelet activation and to diffuse intravascular
coagulation. The result is a swollen, darkened
graft, which undergoes ischemic necrosis. This
type of rejection is generally not reversible, so
prevention is key. Prevention is best done by
making sure the graft is ABO-compatible and by
performing a pretransplant cross-match. The
cross-match is an in vitro test that involves
mixing the donor's cells with the recipient's
serum to look for evidence of donor cell
destruction by recipient antibodies. A positive
cross-match indicates the presence of preformed
antibodies in the recipient that are specific to
the donor, thus a high risk of hyperacute
rejection if the transplant is performed. (See
Schwartz 8th ed., Chapter 10, Transplant
Immunology.)
3
The mechanism of action of azathioprine
is A. Inhibition of calcineurin B. Interference
with DNA synthesis C. Binding of FK-506 binding
proteins D. Inhibition of P7056 kinase
4
Answer B. Explanation Azathioprine (AZA) acts
late in the immune process, affecting the cell
cycle by interfering with DNA synthesis, thus
suppressing proliferation of activated B and T
lymphocytes. AZA is valuable in preventing the
onset of acute rejection, but is not effective in
the treatment of rejection episodes
themselves. Cyclosporine binds with its
cytoplasmic receptor protein, cyclophilin, which
subsequently inhibits the activity of
calcineurin. Doing so impairs expression of
several critical T-cell activation genes, the
most important being for interleukin-2 (IL-2). As
a result, T-cell activation is suppressed. The
metabolism of cyclosporine is via the cytochrome
P450 system, therefore several drug interactions
are possible. Inducers of P450 such as phenytoin
decrease blood levels drugs such as
erythromycin, cimetidine, ketoconazole, and
fluconazole increase them. Tacrolimus, like
cyclosporine, is a calcineurin inhibitor and has
a very similar mechanism of action. Cyclosporine
acts by binding cyclophilins, while tacrolimus
acts by binding FK506-binding proteins (FKBPs).
The tacrolimus-FKBP complex inhibits the enzyme
calcineurin, which is essential for activating
transcription factors in response to the rise in
intracellular calcium seen with stimulation of
the T-cell receptor (TCR). The net effect of
tacrolimus is to inhibit T-cell function by
preventing synthesis of IL-2 and other important
cytokines. Sirolimus (previously known as
rapamycin) is structurally similar to tacrolimus
and binds to the same immunophilin (FKBP). Unlike
tacrolimus, it does not affect calcineurin
activity, and therefore does not block the
calcium-dependent activation of cytokine genes.
Rather, the active complex binds so-called target
of rapamycin (TOR) proteins (Fig. 10-2),
resulting in inhibition of P7056 kinase (an
enzyme linked to cell division). The net result
is to prevent progression from the G1 to the S
phase of the cell cycle, halting cell
division. Mycophenolate mofetil works by
inhibiting inosine monophosphate dehydrogenase,
which is a crucial, rate-limiting enzyme in de
novo synthesis of purines. Specifically, this
enzyme catalyzes the formation of guanosine
nucleotides from inosine. Many cells have a
salvage pathway and therefore can bypass this
need for guanosine nucleotide synthesis by the de
novo pathway. Activated lymphocytes, however, do
not possess this salvage pathway and require de
novo synthesis for clonal expansion. The net
result is a selective, reversible
antiproliferative effect on T and B lymphocytes.
(See Schwartz 8th ed., Chapter 10, Clinical
Immunosuppression.)
5
Lymphoceles occur how long after a renal
transplant? A. Within 48 h B. 1 week after
surgery C. 24 weeks after surgery D. 3 months
after surgery
6
Answer C. Explanation The reported incidence of
lymphoceles (fluid collections of lymph that
generally result from cut lymphatic vessels in
the recipient) is 0.6 to 18. Lymphoceles usually
do not occur until at least two weeks
posttransplant. Symptoms are generally related to
the mass effect and compression of nearby
structures (e.g., ureter, iliac vein, allograft
renal artery), and patients develop hypertension,
unilateral leg swelling on the side of the
transplant, and elevated serum creatinine.
Ultrasound is used to confirm a fluid collection,
although percutaneous aspiration may be necessary
to exclude presence of other collections such as
urinomas, hematomas, or abscesses. The standard
surgical treatment is creation of a peritoneal
window to allow for drainage of the lymphatic
fluid into the peritoneal cavity where it can be
absorbed. Either a laparoscopic or an open
approach may be used. Another option is
percutaneous insertion of a drainage catheter,
with or without sclerotherapy however, it is
associated with some risk of recurrence or
infection. (See Schwartz 8th ed., Chapter 10,
Kidney Transplantaion.)
7
Which of the following is NOT a side effect of
cyclosporine? A. Interstitial fibrosis of the
renal parenchyma B. Gingival hyperplasia
C. Headache D. Pancreatitis
8
Answer D Explanation Adverse effects of
cyclosporine can be classified as renal or
nonrenal. Nephrotoxicity is the most important
and troubling adverse effect of cyclosporine.
Cyclosporine has a vasoconstrictor effect on the
renal vasculature. This vasoconstriction (likely
a transient, reversible, and dose-dependent
phenomenon) may cause early posttransplant graft
dysfunction or may exaggerate existing poor graft
function. Also, long-term cyclosporine use may
result in interstitial fibrosis of the renal
parenchyma, coupled with arteriolar lesions. The
exact mechanism is unknown, but renal failure may
eventually result. A number of nonrenal side
effects may also be seen with the use of
cyclosporine. Cosmetic complications, most
commonly hirsutism and gingival hyperplasia, may
result in considerable distress, possibly leading
to noncompliant behavior, especially in
adolescents and women. Several neurologic
complications, including headaches, tremor, and
seizures, also have been reported. Other nonrenal
side effects include hyperlipidemia,
hepatotoxicity, and hyperuricemia. (See Schwartz
8th ed., Chapter 10, Clinical Immunosuppression.)
9
The 5-year graft survival rate after renal
transplantation is A. 3540 B. 5055
C. 7580 D. 9095
10
Answer C. Explanation The incidence of acute
rejection has declined steadily since the early
1990s. Most centers now report acute rejection
rates of 10 to 20 at 1 year posttransplant. This
decline has been a major factor in the
improvement in graft survival rates, which are
now about 75 to 80 at 5 years and 60 to 65 at
10 years posttransplant for all kidney
recipients. Currently, the most common cause of
graft loss is recipient death (usually from
cardiovascular causes) with a functioning graft.
The second most common cause is chronic allograft
nephropathy. Characterized by a slow, unrelenting
deterioration of graft function, it likely has
multiple causes (both immunologic and
nonimmunologic). The graft failure rate due to
surgical technique has remained at about 2. (See
Schwartz 8th ed., Chapter 10, Kidney
Transplantation.)
11
All of the following are absolute
contraindications in considering a candidate for
orthotopic cardiac transplantation
EXCEPT A. Active infection B. Age over 65 years
C. History of medical noncompliance D. Severe
renal insufficiency
12
Answer A. Explanation Active infection is
considered a potentially reversible
contraindication to cardiac transplantation. The
other conditions listed are absolute
contraindications to orthotopic cardiac
transplantation. Heterotopic cardiac
transplantation, in which the patient's right
heart continues to work against the pulmonary
hypertension while the donor heart supplies
systemic circulation, is used for a certain
number of patients with pulmonary hypertension.
(See Schwartz 7th ed.)
13
After completion of the vascular anastomoses,
drainage of a transplanted pancreas is
accomplished by anastomosis to A. Right colon
B. Left colon C. Duodenum D. Bladder or small
bowel
14
Answer D Explanation Once the pancreas is
revascularized, a drainage procedure must be
performed to handle the pancreatic exocrine
secretions. Options include anastomosing the
donor duodenum to the recipient bladder or to the
small bowel, with the small bowel either in
continuity or connected to a Roux-en-Y limb. Some
centers always use enteric drainage, others
always use bladder drainage, and others tailor
the approach according to the recipient category.
Both enteric drainage and bladder drainage now
have a relatively low surgical risk. The main
advantage of bladder drainage is the ability to
directly measure enzyme activity in the
pancreatic graft exocrine secretions by measuring
the amount of amylase in the urine. A decrease in
urine amylase is a sensitive marker for
rejection, even though it is not entirely
specific. Urine amylase always decreases before
hyperglycemia ensues. A rise in serum amylase may
precede a decrease in urine amylase, but serum
amylase by itself is less sensitive (it does not
always rise, but urine amylase always decreases),
and is no more specific for the diagnosis of
rejection. The leak rate is the same whether the
pancreas is drained to the bladder or to the
bowel, but the consequences of a bladder leak are
much less severe than those associated with a
bowel leak. The disadvantages of bladder drainage
include complications such as dehydration and
acidosis (from loss of alkalotic pancreatic
secretions in the urine), and local problems with
the bladder such as infection, hematuria, stones,
and urethritis. Because of these chronic
complications, between 10 and 20 of
bladder-drained graft recipients are ultimately
converted to enteric drainage. Enteric drainage
is more physiologic and has fewer long-term
complications. However, the ability to monitor
for rejection is decreased, given the absence of
urinary amylase. Rejection in simultaneous
pancreas and kidney (SPK) transplant recipients
almost always affects both the kidney and the
pancreas therefore, the serum creatinine level
can be used as a marker for rejection of the
pancreas. Hence, most centers now use enteric
drainage for SPK transplants. If the kidney and
the pancreas are from different donors, or if a
pancreas transplant alone (PTA) is performed,
then bladder drainage is preferred, so rejection
of the pancreas can be detected earlier. (See
Schwartz 8th ed., Chapter 10, Pancreas
Transplantation.)
15
Absolute contraindications for donation of a
heart include all of the following
EXCEPT A. Carbon monoxide-hemoglobin level gt20
B. Prolonged cardiac arrest C. Prolonged
high-dopamine requirement D. Significant smoking
history
16
Answer C. Explanation The use of high doses of
dopamine for more than 24 h before death is a
relative contraindication to transplantation of
the heart. The other listed items are all
absolute contraindications to cardiac donation.
Severe structural heart disease and human
immunodeficiency virus seropositivity are other
absolute contraindications. (See Schwartz 7th
ed.)
17
The most common cause of renal failure in the
United States is A. Chronic glomerulonephritis
B. Chronic pyelonephritis C. Diabetes mellitus
D. Obstructive uropathy
18
Answer C. Explanation Because the life
expectancy of patients with diabetes mellitus has
dramatically lengthened by appropriate use of
insulin, diabetes is now the leading cause of
renal failure and contributes to blindness,
neuropathies, and early atherosclerosis. These
problems have led to the continued interest in
the possibility of pancreatic transplantation as
a form of disease control. (See Schwartz 7th ed.)
19
A 53-year-old man has long-standing liver
cirrhosis secondary to hepatitis C infection. The
most appropriate screening regimen should
include I. yearly CT scan of the abdomen II. a
liver biopsy III. liver ultrasound IV. AFP
level V. diagnostic laparoscopy A. I, II B. III,
V C. III, IV D. I, V E. II, III
20
Answer C. Explanation The risk factors for
developing HCC are well documented and include
the presence of cirrhosis, chronic active viral
hepatitis associated with elevated AFP, age gt50,
male gender, family history of HCC, and
previously resected or ablated HCC. Once
cirrhosis has developed, HCC is estimated to
occur at the rate of 14 per year. This
well-documented risk for developing HCC has led
to the practice of screening and surveillance of
high-risk patients for HCC. Although there are no
randomized trials comparing surveillance with no
surveillance, a National Institute of Health
Consensus Panel currently recommends the use of
ultrasonography and AFP levels for early
detection of HCC in high-risk populations (Fig.
28-20). FIG. 28-20Routine screening for HCC has
been demonstrated not to be cost-effective
however, the wide availability of color-flow or
power Doppler imaging provides a rapid
noninvasive modality to serially examine the
liver in patients at risk for the development of
HCC. The image depicted illustrates an HCC lesion
with a hallmark arterial feeding vessel
visualized by color-flow Doppler imaging.Serum
markers other than AFP have no proven efficacy
for early detection of HCC, and ultrasound has a
reasonable sensitivity (6078) but is operator
dependent. This combination should be done at 6
months intervals. The identification of HCC by
screening has marginal cost effectiveness.
Despite this, screening for HCC in high-risk
patients has become the standard of care and
should be recommended when applicable. When
viewed from an individual patient's perspective,
screening seems to be worthwhile for good
surgical candidates who can undergo resection or
transplantation. The use of CT scan for this
purpose is not cost-effective, and it is not
currently recommended as a screening tool
although some physicians use it in addition to
AFP levels and ultrasound. Liver biopsy and
laparoscopy may establish the diagnosis of HCC in
high-risk patients but should not be routinely
obtained and have no role as screening tools.
IG. 28-20
21
Which of the following radiologic studies is not
recommended for the diagnosis of Caroli's
disease? A. magnetic resonance imaging (MRI)
abdomen B. CT scan abdomen C. abdominal US
D. HIDA scan E. ERCP
22
Answer D. Explanation Caroli's disease is an
abnormal development of the intrahepatic bile
ducts without an obstructive cause, characterized
by saccular dilatations, resembling a picture of
multiple cyst-like structures of varying size.
Two types have been described a type with bile
duct abnormalities alone and a type with bile
duct abnormality combined with periportal
fibrosis, similar to congenital hepatic fibrosis.
This combined type is also known as Caroli's
syndrome and has been reported more frequently
than the pure type, or Caroli's disease. Caroli's
disease is anatomically characterized for
saccular dilatations of the bile ducts more
frequently seen in the left side of the liver. In
3040 of the cases this are confined to one
segment of one side of the liver. Bilateral
abnormalities are more common in the second type
Caroli's syndrome. The most common complications
are cholangitis, septicemia, amyloidosis, and
cholangiocarcinoma (710 of patients). Caroli's
syndrome is associated with renal disorders such
as renal cysts and nephrospongiosis seen in
3040 of patients. These disorders have not been
seen in Caroli's disease. The diagnosis is made
by radiologic studies such as US, CT scan, ERCP,
MRI where saccular or cystically dilated
intrahepatic ducts are seen. Surgical treatment
is indicated in order to reduce the risk of
recurrent cholangitis, biliary cirrhosis, or
cholangiocarcinoma. Hepatic lobectomy is
indicated for localized bile duct abnormalities
(Caroli's disease), while liver transplant should
be considered in selected patients with
generalized disease or concomitant liver fibrosis
and portal hypertension (Caroli's syndrome).
23
Immunologic rejection is mediated by the
recipient's A. Eosinophils B. Lymphocytes
C. Neutrophils D. Plasma cells
24
Answer B. Explanation Early work in the
transplantation field showed that graft rejection
was mediated by the recipient's white blood
cells. Refinement of the techniques involved
demonstrated that the lymphocytes played the
major role in this phenomenon. The development of
antilymphocyte serum was an early step in
controlling the rejection process. (See Schwartz
7th ed.)
25
In the prevention of graft rejection,
cyclosporine A. Blocks transcription of
interleukin-1 (IL-1) and tumor necrosis factor-
(TNF-) B. Inhibits lymphocyte nucleic acid
metabolism C. Results in rapid decrease in the
number of circulatory T lymphocytes
D. Selectively inhibits T-cell activation
26
Answer D. Explanation There are a number of
different agents used to control graft rejection,
and they function in different ways.
Cyclosporine, the mainstay of immunosuppression,
selectively inhibits T-cell activation.
Corticosteroids block the transcription of IL-1
and TNF-. Azathioprine inhibits lymphocyte
nucleic acid metabolism. Mycophenolate mofetil
inhibits RNA and DNA synthesis. OKT3 results in a
rapid decrease in circulatory T lymphocytes. (See
Schwartz 7th ed.)
27
Required laboratory tests in evaluation of a
patient under consideration for heart
transplantation include all of the following
EXCEPT A. Blood type B. Cardiac catheterization
C. Complete blood count D. Prothrombin time and
activated partial thromboplastin time
28
Answer B. Explanation Cardiac catheterization
may be indicated in some patients to evaluate
cardiac function. The other tests are required in
any patient under consideration for cardiac
transplantation. (See Schwartz 7th ed.)
29
All of the following conditions in a potential
donor are absolute contraindications to the use
of a kidney for transplantation EXCEPT A. Age
older than 70 years B. Chronic renal
insufficiency C. Long-standing hypertension
D. Presence of hepatitis C
30
Answer D. Explanation Cadaveric kidneys make up
75 of all donor kidneys, and the demand far
exceeds the supply. For this reason, donor
criteria have been liberalized in recent years.
Advanced age, chronic renal insufficiency,
intravenous drug abuse, and long-standing
hypertension remain absolute contraindications.
Human immunodeficiency virus seropositivity and
the presence of surface antigens against
hepatitis B are also absolute contraindications.
Although there is risk associated with using a
kidney from a donor with evidence of hepatitis C,
this condition is not considered an absolute
contraindication to kidney use. (See Schwartz 7th
ed.)
31
Absolute contraindications to renal
transplantation for a patient with chronic renal
failure include all of the following
EXCEPT A. Chronic active hepatitis B. Human
immunodeficiency virus infection C. Recent
operation of cancer of the colon D. Sickle cell
disease
32
Answer D. Explanation Sickle cell disease is a
relative contraindication to renal
transplantation because of the associated high
incidence of recurrence. The other listed
conditions are considered absolute
contraindications because of the patient's
generally poor health prognosis. (See Schwartz
7th ed.)
33
The single most important factor in determining
whether to perform a transplant between a
specific donor and recipient is A. Mixed
lymphocyte culture assays of the donor and
recipient B. HLA types of the donor and recipient
C. ABO blood types of the donor and recipient
D. Peripheral T-cell count of the recipient
34
Answer C. Explanation Although mixed lymphocyte
culture assays and HLA typing of the donor and
recipient to determine compatibility have been
shown to enhance long-term graft survival,
immediate graft function has been correlated to
the absence of the presensitized state. This
presensitization can be with respect to
lymphocytotoxic antibodies or preformed
isoagglutinins. ABO compatibility is essential in
renal and cardiac transplantation because
incompatibility leads to prompt destruction of
the transplanted organ. In liver transplantation,
the presensitized state is of less importance,
but diminished graft survival has been
demonstrated in ABO-incompatible combinations.
(See Schwartz 7th ed.)
35
A 24-year-old woman is admitted to the intensive
care unit for sudden collapse with progressive
neurologic deficits. A computed tomography scan
reveals an intracranial tumor with evidence of
acute hemorrhage. Emergent craniotomy is done for
decompression, and tissue obtained reveals
high-grade malignant astrocytoma. On
postoperative day 1, the patient is placed on
large doses of phenobarbital for seizure activity
but continues to deteriorate. On day 3, she
requires dopamine support at 10 mg/kg/min to
maintain a systolic blood pressure of 90 mm Hg.
She develops diabetes insipidus, and her urine
output is adequate, although her creatinine rises
to 1.5 mg/dL and the blood urea nitrogen (BUN) is
40 mg/dL. A urine culture from a Foley specimen
yields Escherichia coli at 100,000/mL. On day 4,
she becomes unresponsive, without evidence of
cortical or brainstem function. An
electroencephalogram (EEG) is isoelectric. Which
of the following is an absolute contraindication
for consideration of this woman as a potential
organ donor? A. Presence of high-grade
intracranial malignancy B. Requirement of pressor
support C. Elevated BUN and creatinine
D. Presence of supratherapeutic phenobarbital
levels
36
Answer D. Explanation The presence of
phenobarbital, narcotics or alcohol, or of
hypothermia is a contraindication to organ
donation, even with an isoelectric EEG. This is
because these factors may suppress spontaneous
electric activity of the brain. Intracranial
tumors are not considered a contraindication,
mainly because of their lack of systemic
metastasis. Other malignancies do contraindicate
donation. The need for pressor is not necessarily
a contraindication, especially if these drugs are
used in the terminal period to maintain blood
pressure and urine output. Elevations of BUN and
creatinine are not uncommon, especially in the
face of diabetes insipidus with prerenal
azotemia. Adequate urine output is the most
important factor in consideration of renal organ
donation. Lower urinary tract infection caused by
instrumentation is not a contraindication to
donation of kidneys, whereas systemic or
peritoneal sepsis is. (See Schwartz 7th ed.)
37
All of the following are side effects of
cyclosporine A administration for prevention of
organ rejection EXCEPT A. Hepatotoxicity
B. Hirsutism C. Tremor D. Bone marrow depression
38
Answer D. Explanation Bone marrow depression has
often been seen with azathioprine but is not seen
in patients on cyclosporine. Hepatotoxicity,
hirsutism, tremor, and nephrotoxicity are
complications of prolonged use of cyclosporine A.
Nephrotoxicity is the most clinically important
and most frequently seen side effect and may
limit the drug's use in some patients. (See
Schwartz 7th ed.)
39
Currently, which of the following infectious
illnesses is most likely to compromise patients
after renal transplantation? A. Coli sepsis
B. Pneumococcal sepsis C. Candidiasis
D. Cytomegalovirus sepsis
40
Answer D. Explanation Immunosuppression for
transplantation increases the risk for all types
of infection. Use of cyclosporine, along with
broad-spectrum antibiotics, has reduced the
incidence of bacterial infections. Most serious
posttransplant infections arise when rejection is
being treated, and in the past, these led to high
mortality. Both Candida and Aspergillus
infections can occur but are relatively rare
compared with viral infection. Cytomegalovirus
(CMV) can produce a spectrum of illness
characterized by fever, neutropenia, arthralgias,
malaise, gastrointestinal ulcerations, and
decreased renal function. CMV itself produces a
state of immunosuppression, and many serious
infections are superinfections in patients
already experiencing CMV infections. Treatment of
CMV sepsis includes decreasing immunosuppression
and administering ganciclovir, a new antiviral
drug. (See Schwartz 7th ed.)
41
Postoperative indicators of primary nonfunction
of a liver allograft include all of the following
EXCEPT A. Hypokalemia B. Hypoglycemia
C. Elevated prothrombin time D. Alkalosis
42
Answer A. Explanation Primary graft failure is
a very serious complication. The patient
decompensates quickly, and urgent transplantation
is indicated. Severe central nervous system
changes, with acid-base changes (early alkalosis
due to inability to metabolize citrate and
acidosis as a terminal event), hyperkalemia,
coagulopathy, hypoglycemia, and oliguria are
often terminal events of this acute hepatic
decompensation. (See Schwartz 7th ed.)
43

• An absolute contraindication to cardiac
  transplantation is
• Active peptic ulcer disease
• Age older than 60 years
• Fixed pulmonary vascular resistance
• Heavy cigarette smoking

44
Answer C. Explanation Although the other three
items are relative contraindications to cardiac
transplantation, fixed pulmonary vascular
resistance is the only absolute contraindication
among those listed. A heart accustomed to low
pulmonary artery pressure and resistance will
fail immediately if placed in a recipient with
fixed pulmonary vascular resistance. (See
Schwartz 7th ed.)
45
A 45-year-old female underwent a kidney
transplant 6 months ago and has been taking
cyclosporine and steroids. She developed
cholelithiasis and requires a laparoscopic
cholecystectomy. She wants to know if her chance
to have a wound infection is increased. The best
answer to her question is A. No, steroids and
cyclosporine do not increase the chance to have
wound infection when used chronically B. Yes,
because of inhibition of collagen synthesis and
fibroblast proliferation C. Yes, because of
persistent vasoconstriction and hypoxia D. Yes,
because of structural nuclear changes and
decreased DNA synthesis E. Yes, mainly because of
cyclosporine, which blocks IL-2 and decrease
migration of macrophages
46
Answer B. Explanation During the past two
decades the survival rate of solid organ
recipients has improved dramatically. The major
factor in improved clinical outcome is the
decline in death secondary to infection.
Currently, 1-year mortality caused by infection
has decreased to less than 5 for renal
transplant patients. Better immunosuppression and
understanding by the clinician of drug
pharmacodynamics and pharmacokinetics are
responsible for decrease morbidity and mortality
after solid organ transplantation. Steroids
reduce the inflammatory process blocking
transcription of cytokine genes (especially IL-1)
leading to nonspecific inhibition of T
lymphocytes and macrophages. It is well
documented that steroids decrease fibroblast
migration and collagen synthesis. Topical
steroids also inhibit wound healing. Cyclosporine
is a potent immunosuppressant used to suppress
transplant rejection. Experimental evidence
suggests that the effectiveness of cyclo-sporine
is because of specific and reversible inhibition
of immunocompetent lymphocytes in the G0- or
G1-phase of the cell cycle. T lymphocytes are
preferentially inhibited. The T-helper cell is
the main target, although the T-suppressor cell
may also be suppressed. Cyclosporine also
inhibits lymphokine production and release of
IL-2. Cyclosporine does not significantly affect
hydroxyproline content and macrophages migration,
although there is some evidence that cyclosporine
impairs wound healing. Studies in rats have shown
that activin- expression and matrix
metalloproteinases (MMPs) activity by fibroblast
is reduced. BIBLIOGRAPHYMulder GD et al. Factors
complicating wound repair. In McCulloch JM,
Kloth LC, Feedar JA (eds.), Wound Healing
Alternatives in Management, 2nd ed. Philadelphia,
PA FA Davis, 1996, 51. Petri JB, Schurk S,
Gebauer S, Haustein U. Cyclosporine A delays
wound healing and apoptosis and suppresses
activin BA expression in rats. Eur J Dermatol
19988(2)104113.  PubMed 9649703
47
The best method of monitoring the development of
acute rejection in a patient after cardiac
transplantation is A. Dipyridamole thallium study
B. Electrocardiogram C. Endomyocardial biopsy
D. Ultrasound examination of the heart
48
Answer C. Explanation It would be desirable to
follow possible rejection by some noninvasive
procedure, but none has given timely results.
Endomyocardial biopsies allow rejection to be
diagnosed before significant organ damage and
dysfunction occur. (See Schwartz 7th ed.)
49
You are caring for a 50-year-old man who is 3
years out from a cadaveric renal transplant for
diabetic nephropathy. He had a single episode of
vascular rejection 1 month after transplant, but
otherwise has done well with a baseline serum Cr
of 1.8 mg/dL. He is admitted to your service with
increasing fatigue, dyspnea with exertion, and
acute renal failure. His medications include
cyclosporine, mycophenolate mofetil, prednisone,
and nifedipine. On examination, he is pale and
weak with a BP of 150/95 mmHg and a pulse of
110/min. He has a few scattered ecchymoses on his
skin, but otherwise the examination is
normal. Laboratory values 3 months ago Laboratory
findings on admission Na   142 Na   144 K  
4.8 K   6.7 Cl   105 Cl   110 HCO3   25
HCO3   17   BUN 30 BUN 68 Cr 1.8 Cr 5.8 LDH
150 LDH 650 Bili 0.7 Bili 2.9 Alb 3.9 Alb 3.5
AlkP 78 AlkP 80 WBC 8 WBC 14 Hb 11 Hb 5 Hct 33
Hct 15 Plts 221 Plts 45 U/A trace pro U/A 2
protein No cells     2030 RBC/Hpf Laboratory
values 3 months ago Laboratory findings on
admission Na   142 Na   144 K   4.8 K  
6.7 Cl   105 Cl   110 HCO3   25
HCO3 Which of the following is the most
appropriate step in the evaluation of your
patient? A. schedule a renal biopsy B. give IV
pulse steroids C. order a renal ultrasound
D. obtain a right upper quadrant (RUQ) ultrasound
E. review the peripheral smear looking for
schiztocytes
50
Answer E. Explanation The patient has a
hemolytic anemia (elevated LDH and bilirubin),
thrombocytopenia, and renal failure. Therefore,
the patient meets the criteria of HUS. The most
important next step would be to obtain a
peripheral smear to document the presence of
schiztocytes. HUS is usually seen in children
with bloody diarrhea associated with infection
with verotoxin producing E. coli from undercooked
meat however, HUS is also seen in a variety of
conditions including malignancy, scleroderma
renal crises, bone marrow transplantation, and
the administration of the immunosuppressants
cyclosporine A and tacrolimus. In renal
transplantation, cyclosporine associated HUS may
develop in up to 10 of patients. Treatment is
removal of the offending agent. Small case series
suggest that plasma exchange may be
helpful. Bibliography Zarifian A, Meleg-Smith S,
O'Donovan R, et al. Cyclosporine-associated
thrombotic microangiopathy in renal allografts.
Kidney Int 19995524572466.  PubMed 10354295
51
All of the following examination findings are
consistent with a diagnosis of brain death
except A. dilated and nonreactive pupils
B. absent oculocephalic reflex C. extensor
(decerebrate) posturing D. absent gag reflex
52
Answer C. Explanation There are two reasons to
declare that a patient is brain dead. The first
is to allow for organ donation, and the second is
to allow for removal of life support mechanisms
once it is deemed that further medical treatment
is futile. Most state governments and hospitals
refer to the guidelines established by the
President's Commission for the determination of
brain death. For older children and adults, the
physical examination must show absence of
cerebral and brain stem function, no response to
deep central pain, and absence of complicating
conditions such as hypothermia or hypotension.
Findings consistent with absence of brain stem
function are dilated and nonreactive pupils,
absent corneal reflexes, absent oculocephalic
(doll's eyes) reflex, absent oculovestibular
reflex, and absent oropharyngeal (gag) reflex. In
addition to these, the apnea test is used to
assess the function of the medulla. Brain death
is confirmed if the patient has no spontaneous
respirations after allowing the PaCO2 to reach
greater than 60 (hypercapnia of this degree will
always produce spontaneous respirations in a
patient with a functioning brain stem). If a
patient has extensor (decerebrate) or flexor
(decorticate) posturing in response to deep
central pain, then information from the brain
stem is still being transmitted down through the
spinal cord which is incompatible with a
diagnosis of brain death. Additionally, a patient
should be free of any complicating condition that
may simulate brain death. Such conditions include
hypothermia, hypotension, intoxication, anoxia,
immediate postresuscitation state, and patients
emerging from a pentobarbital coma. Certain
observation periods ranging from 6 to 24 h may
also be warranted depending on the specific
circumstances. For children less than 5 years of
age coma and apnea must coexist, and there must
be absence of brainstem function on physical
examination. Additional criteria include two
examinations and two negative electroencephalogram
s (EEG) 48 h apart for children age 7 days to 2
months, two examinations and two negative EEGs 24
h apart for children age 2 months to 12 months,
and an interval of 12 h between examinations and
EEGs for children age 12 months to 5 years.
Besides EEG, other confirmatory tests for
diagnosing brain death include cerebral
angiography and radionuclide blood flow studies.
These studies may be helpful in patients with
severe congestive heart failure or chronic
obstructive pulmonary disease where the apnea
test is invalid, in patients with severe facial
trauma which would preclude cranial nerve
testing, in patients coming out of a
pentobarbital coma, and in allowing more
expedient organ donation. BIBLIOGRAPHYPresident's
Commission for the study of ethical problems in
medicine guidelines for the determination of
death. JAMA 198124621842186.  PubMed
16429157Task force for the determination of
brain death in children guidelines for the
determination of brain death in children. Arch
Neurol 198744587588.
53
Characteristics of fulminant hepatic failure are
as follows I. It is rarely a medical
emergency. II. It is a clinical syndrome
representing a final common pathway for a wide
variety of diseases. III. It is most commonly
because of alcohol abuse. IV. It has
pathognomonic features making the diagnosis
evident. V. Sometimes may not have an
identifiable cause. A. III, IV B. III, V C. II,
III D. IV, V E. II, V
54
Answer E. Explanation Acute fulminant hepatic
failure is an uncommon manifestation of liver
disease that constitutes a medical emergency. It
is because of loss of hepatic parenchyma
secondary to a given insult and carries a grave
prognosis (Fig. 28-9).
55
A 33-year-old man tested positive for antibody to
HCV when donating blood. His liver enzymes are
within normal range. The patient is otherwise
healthy, feels well, and denies any risk factors
for HCV. His physical examination is unremarkable
and shows no stigmata of chronic liver disease.
Qualitative polymerase chain reaction (PCR)
testing is positive for HCV RNA. Which of the
following actions is most appropriate for this
patient? A. reassure the patient that he does not
have chronic HCV infection and requires no
further evaluation or treatment B. recommend
treatment with antiviral therapy for chronic HCV
infection C. recommend liver biopsy and initiate
therapy accordingly D. recommend yearly follow-up
with liver enzymes monitoring and do not initiate
any treatment at this time E. recommend liver
imaging consisting of an ultrasound or CT
56
Answer D. Explanation Screening recommendations
for HCV are currently practiced according to the
Centers for Disease Control recommendations. The
main transmission mode is following initiation of
injection drug use, whereas the risk of sexual
transmission is low. The accuracy of anti-HCV
testing (enzyme immunoassay) depends on the
pretest probability of disease. The predictive
value in a patient with known parenteral exposure
exceeds 90, whereas the predictive value of a
positive anti-HCV test in blood donors with a
normal alanine aminotransferase (ALT) level and
no risk factor for HCV infection is less than
50. In this situation, direct measurement of HCV
RNA by PCR assay is required. Seventy to 85 of
patients initially infected with HCV develop
persistent infection. In approximately 15 of
patients, HCV infection resolves within 16
months, possibly because of HCV-specific T-cell
function. Of those patients with persistent
infection, 20 have chronic viremia with normal
liver enzymes. In this group of patients, risk of
progression to cirrhosis is low. On the other
hand, patients with a consistently or
intermittently elevated ALT level have a 20 risk
of developing cirrhosis over 20 years. The risk
of hepatic decompensation manifesting as ascites,
variceal bleed, encephalopathy, or loss of
hepatic synthetic ability averages about 35 per
year. Moreover, in the cirrhotic patient, the
risk of hepatoma is in the range of 14 per
year. The decision to perform a liver biopsy
should be individualized. It may provide useful
information in a middle aged individual with long
standing HCV infection and clinical features of
advanced liver disease. Treatment is indicated
for patients with significant inflammation or
fibrotic disease. There are two Food and Drug
Administration (FDA) approved therapies for
chronic hepatitis C interferon monotherapy and
the combination of interferon with ribavirin.
Sustained response after discontinuation of
therapy is 515 with monotherapy and 3540 with
combination treatment.
57
Which of the following dietary changes will
improve the Child-Pugh classification in
end-stage liver patients with protein-calorie
malnutrition? A. lactoalbumin supplementation
B. oral intake of fat soluble vitamin K
C. maltodextrin supplementation D. branched chain
amino acid supplementation E. long-term
parenteral nutrition
58
Answer D. Explanation Malnutrition in the
end-stage liver failure patient plays a
significant role in outcome. The nutritional
deficiencies are mainly because of protein
malnutrition and have been shown to be an
independent risk factor for mortality and
life-threatening complication. The factors
causing the protein loss and failure of intake
are the hypermetabolism associated with end-stage
liver failure necessitating a greater protein
intake. A protein load in these patients can, in
turn, lead to worsening encephalopathic
changes. Branched chain amino acid supplements
have been used successfully in cirrhotic patients
to increase the protein intake to combat nitrogen
losses, while avoiding encephalopathic
changes. Long-term studies assessing the benefits
of oral branched chain amino acid supplementation
in these patients have found that there is no
statistically significant difference in
mortality. When compared with equivalent caloric
and protein oral supplementation there have been
shown to be significant improvements in
Child-Pugh score, number of required hospital
admissions, bilirubin, anorexia, and
health-related quality of life. Nutritional
support with branched chain amino acids has
improved anthropometric measurements in this
subset of malnourished patients and this
correction has been proven to prolong life. The
major downside to branched chain amino acid
supplementation is that the supplements are
notoriously unpalatable and this had led to
noncompliance and patient withdrawal from
trials. BIBLIOGRAPHYFabbri A, Magrini N, Bianchi
G, et al. Overview of randomized clinical trials
of oral branched-chain amino acid treatment in
chronic hepatic encephalopathy. JPEN J Parenter
Enteral Nutr 199620159164.  PubMed
8676537Italian multicentre cooperative project
in nutrition in liver cirrhosis. Nutritional
status in cirrhosis. J Hepatol 199421317325.
Marchesini G, Bianchi G, Merli M, et al.
Nutritional supplementation with branched-chain
amino acids in advanced cirrhosis a
double-blind, randomized trial. Gastroenterology
200312417921801.  PubMed 12806613Plauth M,
Merli M, Kondrup J, et al. ESPEN guidelines for
nutrition in liver disease and transplantation.
Clin Nutr 1997164355.
59
A 25-year-old female is brought to the local
emergency room with signs and symptoms compatible
with encephalopathy. Her family members report
that she had been jaundiced over the past few
days and had recently separated with her
boyfriend. She had been otherwise healthy and on
no medications. The most likely etiology and best
treatment course include the following. I.
Hepatic failure in this setting is usually
secondary to viral hepatitis. II. The patient
should receive broad-spectrum prophylactic
antibiotics III. Steroid therapy should be
started immediately. IV. An evaluation for liver
transplantation should be done as soon as
possible. V. Acetylcysteine should be
administered. A. II, IV B. I, V C. I, II, III
D. III, V E. IV, V
60
Answer E. Explanation The time course of
fulminant hepatic failure has an etiologic and
prognostic significance. An illness of 1 week or
less before the development of failure is usually
suggestive of hepatic ischemia or acetaminophen
toxicity. On the other hand, illness longer than
4 weeks is more likely the result of viral
hepatitis or hepatic failure of unknown
etiology. Patients who are ill for more than 8
weeks before they develop encephalopathy have a
higher chance of developing portal hypertension,
whereas patients with illness of shorter duration
(lt4 weeks) are more likely to develop cerebral
edema. Encephalopathy preceded by 1 week of
jaundice is a poor prognostic indicator. Because
of its easy availability, acetaminophen is a
commonly used drug for suicide. This is also a
problem with other over-the-counter remedies that
contain acetaminophen as an active
ingredient. Although infectious complication may
develop in up to 80 of patients with fulminant
hepatic failure, prophylactic antibiotic therapy
is still controversial. A wide variety of
therapies have been proposed and used for the
treatment of this disease, including
corticosteroids, prostaglandins, and exchange
transfusion, yet none have proved efficacious.
Only the development of liver transplantation has
allowed the salvage of patients with irreversible
liver failure. Patients should therefore be
evaluated for liver transplantation as soon as
possible and placed on the transplant waiting
list. Treatment is otherwise supportive and
includes prophylaxis for gastrointestinal
bleeding in the setting of coagulopathy,
correction of hypoglycemia, intracranial pressure
(ICP) monitoring of intracranial hypertension,
along with osmotherapy and barbiturates,
hemodynamic monitoring and organ-directed support
if multiorgan failure develops. Surveillance
cultures should be routinely obtained and if
infection is suspected, empirical therapy should
be tailored to local hospital antimicrobial
sensitivities and should cover Staphylococcus and
gram-negative aerobes.
61
A 26-year-old surgery resident is evaluated for
malaise, fatigue, myalgia, and low-grade fever.
He was previously well and denies illicit drug
use, transfusions, or recent travel. He admits
though to multiple needle stick accidents.
Physical examination reveals jaundice and
hepatomegaly. Laboratory studies are as follows
AST 1000 U/L, ALT 2000 U/L, INR 1.0, total
bilirubin 4 mg/dL, IgG anti-HAV positive, IgM
anti-HAV negative, HBsAg positive, IgG anti-HBc
positive, IgM anti-HBc positive, anti-HCV
negative. The most likely diagnosis is A. acute
hepatitis C B. acute hepatitis B C. chronic
hepatitis A D. chronic hepatitis B E. chronic
hepatitis C
62
Answer B. Explanation HBV is primarily
transmitted by parenteral and mucous membrane
exposure to infectious body fluids such as blood,
serum, semen, and saliva. Risk factors include
close personal or intimate exposure to an
infected household contact or sexual partner,
intravenous drug use, tattooing and body
piercing, unapparent blood inoculations as with
shared razor blades, blood transfusion or
exposure to blood products, hemophilia and
hemodialysis, and work in the health care
profession. Because of improved screening of
blood donors, and educational efforts to combat
human immunodeficiency virus (HIV), the incidence
of HBV infection has declined in the United
States since 1991. Diagnosis of acute hepatitis
depends on the results of specific antiviral
serology. Hospitalization is warranted for
intractable symptoms of anorexia, vomiting, or
severe impairment of liver function. Other
symptoms include jaundice, weight loss, and
malaise. Severe hepatic dysfunction manifests as
renal failure, metabolic acidosis,
encephalopathy, variceal bleeding or ascites. In
adults, more than 90 of HBV infection results in
self-limited acute hepatitis with subsequent
resolution of the disease in 36 months.
Approximately 5 of patients will develop chronic
hepatitis, and 12 will progress to fulminant
hepatitis. IgM antibody to hepatitis B core
antigen is the most specific marker for diagnosis
of acute hepatitis B. Development of antibody to
hepatitis B surface antigen signifies resolution
of the acute infection and is the marker for cure
and immunity to HBV infection. The pattern of
negative HBsAg, positive anti-HBsAg, and positive
anti-HBc assays is seen during the recovery phase
following acute hepatitis B. This antibody
pattern may persist for years and is not
associated with liver disease or infectivity.
Coinfection with delta agent, an incomplete virus
requiring HBsAg for replication, is associated
with severe hepatitis and higher likelihood of
fulminant hepatic failure. Treatment is primarily
supportive and consists of rest, fluids, and
maintenance of adequate nutrition. Antiviral
therapy is currently not recommended for acute
hepatitis B in patients with preexisting HBsAg or
anti-HBs. In patients with parenteral and sexual
exposure, blood should therefore be tested for
hepatitis B surface antigen and antibody to
hepatitis B surface antigen prior to hepatitis B
immune globulin (HBIG) administration. Coadministr
ation of hepatitis B vaccine with HBIG is
recommended for susceptible individuals
sustaining parenteral or sexual exposure and for
all neonates born to HBV positive
mothers. Vaccination with the hepatitis B vaccine
(genetically manufactured HBsAg particles with
HBV DNA or core antigen) is universally
indicated, with the initial dose given at birth
and repeated at 1 and 6 months of age. It is
associated with the development of anti-HBs
antibody alone.
63
About Caroli's disease, mark the correct
answer(s). A. It is characterized by intrahepatic
bile duct atresia. B. Abdominal mass and weight
loss are the most common initial symptoms. C. It
is a developmental anomaly of the ductal plate
characterized by saccular dilatations of the
large bile ducts. D. It is more commonly seen in
adult females. E. It is a risk factor for the
development of cystadenocarcinoma of the bile
duct.
64
Answer C. Explanation Caroli's disease is an
abnormal development of the intrahepatic bile
ducts without an obstructive cause, characterized
by saccular dilatations, resembling a picture of
multiple cyst-like structures of varying size.
Two types have been described a type with bile
duct abnormalities alone and a type with bile
duct abnormality combined with periportal
fibrosis, similar to congenital hepatic fibrosis.
This combined type is also known as Caroli's
syndrome and has been reported more frequently
than the pure type, or Caroli's disease. Caroli's
disease is anatomically characterized for
saccular dilatations of the bile ducts more
frequently seen in the left side of the liver. In
3040 of the cases this are confined to one
segment of one side of the liver. Bilateral
abnormalities are more common in the second type
Caroli's syndrome. The most common complications
are cholangitis, septicemia, amyloidosis, and
cholangiocarcinoma (710 of patients). Caroli's
syndrome is associated with renal disorders such
as renal cysts and nephrospongiosis seen in
3040 of patients. These disorders have not been
seen in Caroli's disease. The diagnosis is made
by radiologic studies such as US, CT scan, ERCP,
MRI where saccular or cystically dilated
intrahepatic ducts are seen. Surgical treatment
is indicated in order to reduce the risk of
recurrent cholangitis, biliary cirrhosis, or
cholangiocarcinoma. Hepatic lobectomy is
indicated for localized bile duct abnormalities
(Caroli's disease), while liver transplant should
be considered in selected patients with
generalized disease or concomitant liver fibrosis
and portal hypertension (Caroli's syndrome).
65
Which of the following is not a complication of
Caroli's disease? A. stone formation B. recurrent
cholangitis C. septicemia D. cholangiocarcinoma
E. amyloidosis F. renal disorders
66
Answer F. Explanation Caroli's disease is an
abnormal development of the intrahepatic bile
ducts without an obstructive cause, characterized
by saccular dilatations, resembling a picture of
multiple cyst-like structures of varying size.
Two types have been described a type with bile
duct abnormalities alone and a type with bile
duct abnormality combined with periportal
fibrosis, similar to congenital hepatic fibrosis.
This combined type is also known as Caroli's
syndrome and has been reported more frequently
than the pure type, or Caroli's disease. Caroli's
disease is anatomically characterized for
saccular dilatations of the bile ducts more
frequently seen in the left side of the liver. In
3040 of the cases this are confined to one
segment of one side of the liver. Bilateral
abnormalities are more common in the second type
Caroli's syndrome. The most common complications
are cholangitis, septicemia, amyloidosis, and
cholangiocarcinoma (710 of patients). Caroli's
syndrome is associated with renal disorders such
as renal cysts and nephrospongiosis seen in
3040 of patients. These disorders have not been
seen in Caroli's disease. The diagnosis is made
by radiologic studies such as US, CT scan, ERCP,
MRI where saccular or cystically dilated
intrahepatic ducts are seen. Surgical treatment
is indicated in order to reduce the risk of
recurrent cholangitis, biliary cirrhosis, or
cholangiocarcinoma. Hepatic lobectomy is
indicated for localized bile duct abnormalities
(Caroli's disease), while liver transplant should
be considered in selected patients with
generalized disease or concomitant liver fibrosis
and portal hypertension (Caroli's
syndrome). Bibliography Porte R, Clavien PA.
Cystic diseases of the biliary system. In On
Diseases of the Gallbladder and Bile Ducts.
Oxford, UK Blackwell Science, 2001, 216225.
67
Which of the following (Fig. 29-3) is not
considered a risk factor for cholangiocarcinoma
development? FIG. 29-3A. primary sclerosing
cholangitis B. Caroli's disease C. choledocal
cyst D. biliary atresia E. hepatolithiasis
68
Answer D. Explanation Cholangiocarcinoma is an
uncommon cancer found in 0.010.2 of all
autopsies. The majority of the patients are older
than 65-year-old with a male predominance. The
etiology is unknown, but several predisposing
conditions have been identified 1. Primary
sclerosing cholangitis have a 630 chance of
developing it and 1030 of patients who undergo
liver transplant for PSC have an occult
cholangiocarcinoma. (See Fig. 29-3.) 2.
Congenital biliary cystic disease (Caroli's
disease, choledochal cyst) have a 1520 chance
of cancer. 3. Hepatolithiasis (recurrent pyogenic
cholangitiohepatitis or oriental
cholangiohepatitis), prevalent in Japan,
secondary to chronic portal bacteremia and portal
phlebitis which may give rise to intrahepatic
pigment stone formation. 4. Biliary parasites,
especially Clonorchis sinensis and Opisthorchis
viverrini, are associated with an increased
risk. 5. Carcinogens such as thorium, radon,
nitrosamines, dioxin, and asbestos. Different
classifications have been used to describe this
tumor. Anatomically they can be divided in intra-
and extrahepatics, where 94 of the
cholangiocarcinomas are extrahepatics and
perihiliar (67). The most commonly used
classification is the Bismuth classification,
which describes the tumor in perspective to the
bile duct bifurcation and has direct implication
on the surgical strategy. Bismuth 1 Tumor below
hepatic bifurcation and can be treated with bile
duct resection alone. Bismuth 2 Tumor that
reaches the bifurcation. They usually require a
caudate lobe resection, in addition to bile duct
resection. Bismuth 3a They may reach the second
intrahepatic division of the right main
duct. Bismuth 3b They extend to the left main
bile duct. Both require either a right or left
hemihepatectomy with bile duct resection. Bismuth
4 Affects both main bile ducts. Surgery is not
an option in this type of location.
69
A patient is brought to the ER 3 months following
liver transplantation. The patient had been doing
well until about 1 week prior to admission when
he because confused, tremulous and complained of
unsteadiness and difficulty with vision. An MR
scan showed T2 hyperintense lesions in both
occipital lobes (Fig. 35-18). The most likely
diagnosis is FIG. 35-18 Axial T2-weighted MRI of
the brain, revealing white matter hyperintensity
in both occipital lobes. A. Creutzfeldt-Jakob's
disease (prion disease) B. cyclosporin toxicity
C. PML D. posttransplantation lymphoma
70
Answer B. Explanation Cyclosporin toxicity can
result in the posterior leukoencephalopathy
syndrome. There are a variety of acute illnesses
that can result in a reversible encephalopathy
secondary to edema of the cerebral white matter,
most prominently in the occipital and posterior
parietal and temporal regions of the brain.
Clinically the syndrome is manifested by the
subacute onset of headache, lethargy, confusion,
altered mental status, seizures, and difficultly
with vision. The white matter edema is visible as
decreased attenuation on CT scans and
hypointensity on T1 and hyperintensity on T2 MR
scans. Originally described in encephalopathy
associated with malignant hypertension and
eclampsia of pregnancy, the syndrome also occurs
secondary to toxicity of cyclosporin and other
immunosuppressants. White matter edema results
from disruption of the blood-brain barrier. The
mechanism for this disturbance is not entirely
clear in cases of immunosuppression. The syndrome
can occur with levels of drug in the therapeutic
range and is probably the result of a
vasculopathy caused by the medication. The
syndrome is reversible by discontinuing or
lowering the drug level. The radiologic
abnormalities often resolve completely within
several weeks. Creutzfeldt-Jakob's disease is a
prion (proteinaceous infectious particle) disease
that results in an invariably fatal
encephalopathy manifested by dementia, ataxia,
myoclonic jerks, and visual symptoms.
Creutzfeldt-Jakob's disease is not associated
with immunosuppression. PML is a white matter
infection of the brain caused by the polyomavirus
in patients who are immunosuppressed and with
certain malignancies. Mental symptoms as well as
blindness can occur. The disease is rapidly
progressive. Imaging studies show areas of white
matter hypointensity on CT and low signal on T1
and high signal on T2 images. There is no
enhancement and little if any mass effect.
Primary central nervous system lymphoma occurs in
patients with AIDS and in patients who have had
organ transplantation and are immunosuppressed. Bi
bliography Hinchey J, Chaves C, Appignana B, et
al. A reversible posterior leukoencephalopathy
syndrome. N Engl J Med 1996334494500.
 PubMed 8559202Truwit C, Denaro C, Lake J,
et al. MR imaging of reversible cyclosporin
A-induced neurotoxicity. Am J Neuroradiol
199112651659.  PubMed 1882738