Vol. 28 No.
10 October 2005
What’s New in ACP Medicine
DAVID C. DALE, MD, FACP, Editor-in-Chief DANIEL D. FEDERMAN, MD, MACP, Founding Editor
WENDY LEVINSON, MD, FACP, Associate Medical Editor, What’s New in ACP Medicine
PRACTICE OF
MEDICINE
New-Onset Seizures
JERRY S. WOLINSKY, MD
JEREMY D. SLATER, MD
University of Texas Health Science
Center at Houston
uly is an interesting and exciting
J time at the medical center. On the
first of the month, the knowledge
base of the house staff changes dra-
matically, as a large proportion of the
most experienced physicians in train-
ing are replaced by eager and anxious
new faces. Suddenly the attending
physician is faced with a flurry of
questions about common problems
that were seldom still asked just a few
days before. On a neurology consulta-
tion service, many of the questions are
predictable, being heavily slanted to
those common conditions for which
our advice is often sought. This year it
was comforting to have some new
data to help with one of those fre-
quently asked questions: what should
be done for patients who present with
new-onset seizures?
About 10% of the general popula-
tion can be expected to have one or
more seizures over the course of a life-
time. Roughly half of those who expe-
rience one seizure will go on to have
additional seizures. Thus, it is not sur-
prising that this question arises fairly
often in any active emergency depart-
ment or acute care setting. Once the
drama surrounding the acute seizure
has settled, these patients require a
well-considered decision as to whether
to initiate drug therapy or continue
the anticonvulsants that were started
continued on page 2
THIS MONTH’S UPDATES
1 CARDIOVASCULAR MEDICINE erosclerosis reduces the likelihood of
progression of atherosclerosis and also
helps prevent adverse cardiovascular
XVI Peripheral Arterial Disease
MARK A. CREAGER, MD
events. Patients who stop smoking cig-
arettes have a more favorable progno-
Harvard Medical School and Brigham
and Women’s Hospital sis than those who continue to smoke.
Aggressive lipid-lowering therapy
Calculating the Odds for
Claudication
reduces progression of peripheral ath-
erosclerosis, but it has not been estab-
lished that it prevents progression of
yslipidemia, particularly hypercho-
D lesterolemia, is present in 40% of
patients with peripheral atherosclero-
symptoms from claudication to critical
limb ischemia. Cholesterol-lowering
therapy with statin drugs reduces ad-
sis. The relative risk of peripheral verse cardiovascular events in patients
arterial disease is 1.2 to 1.4 for each
with atherosclerosis and may improve
40 to 50 mg/dl increase in total cho- walking ability.1-4
lesterol. Hypertriglyceridemia and an
elevated plasma concentration of continued on page 3
lipoprotein(a) each increase the risk of
developing peripheral arterial disease.
Hypertension increases the risk of
claudication by at least twofold in In This Issue
men and by fourfold in women.
Practice of Medicine
Hyperhomocysteinemia has emerged New-Onset Seizures 1
as an important risk factor for athero-
1 Cardiovascular Medicine
sclerosis and increases the risk of
XVI Peripheral Arterial Disease 1
peripheral atherosclerosis by twofold
4 Gastroenterology
to threefold. Elevations in markers of
IX Cirrhosis of the Liver 3
inflammation, including levels of C- XII Diverticulosis, Diverticulitis, and
reactive protein and soluble intercellu- Appendicitis 4
lar adhesion molecule–1, are also 11 Neurology
independent predictors of the develop- XIV Pain 4
ment of symptomatic peripheral arter-
15 Rheumatology
ial disease in otherwise healthy men.1 III Seronegative Spondyloarthritis 5
1. Pradhan AD, Rifai N, Ridker PM: Soluble inter-
cellular adhesion molecule–1, soluble vascular adhe- Clinical Essentials
sion molecule–1, and the development of sympto- I On Being a Physician 6
matic peripheral arterial disease in men. Circulation II Contemporary Ethical and Social
106:820, 2002 [PMID 12176954] Issues in Medicine 6
A Systemic Approach to the 12 Oncology
XVIII Head and Neck Cancer 7
Periphery CDC Recommendation Report
n patients with peripheral arterial dis-
I ease, treatment of risk factors for ath-
Influenza Vaccine Preview 2005–2006 7
2 What’s New in ACP Medicine • October 2005
PRACTICE OF MEDICINE
continued from page 1
in the “heat of battle”—a decision
complicated by the fact that most
new-onset seizures lack readily defined
causes. Before making this decision, it
is worth reviewing the first reported
analysis of a randomized, unmasked,
pragmatic trial comparing immediate
treatment with deferred treatment,
which was conducted by the Medical
Research Council Multicentre Study of
Early Epilepsy and Single Seizures
(MESS) Study Group.1
Of 1,847 patients invited to partici-
pate in this trial, 1,443 were random-
ized either to receive immediate treat-
ment with an anticonvulsant chosen
by the treating physician or to have
treatment deferred pending the devel-
opment of subsequent seizures or
other indications for initiating therapy.
Nearly half of the patients were
recruited in the United Kingdom; the
remainder were seen at centers scat-
tered across Europe, Israel, Brazil, and
Chile. The overwhelming majority of
patients in the study were in their late
teenage years or were young adults. In
all cases, the patient had an adequate-
ly documented history of one or more
clinically definite, spontaneous, and
unprovoked epileptic seizures; the
patient had not been treated with anti-
convulsants before, except for acute
management of the presenting event;
and both the treating physician and
the patient were uncertain whether to
initiate long-term therapy.
When immediate therapy was
given, carbamazepine and valproate
were the most frequently selected anti-
convulsants. Immediate therapy
increased the time to the first seizure,
the second seizure, and the first tonic-
clonic seizure; and it reduced the time
to achieve a 2-year remission of
seizures. Early treatment did not influ-
ence the proportion of patients who
were seizure free 3 and 5 years after
randomization. Two years after ran-
domization, about equal numbers of
patients in the immediate-treatment
group and the deferred-treatment
group (just under 10% of respondents
to a quality-of-life questionnaire)
reported that they were not in school
full-time or employed because of
seizures. By 6 years after randomiza-
tion, nearly half of all patients were on
anticonvulsant therapy, regardless of
whether treatment was started imme-
diately or was deferred. Of patients
randomized to deferred treatment,
between 60% and 70% of those who
had an additional seizure on follow-up
did so within 6 months of study entry;
the risk of an additional seizure was
1.7-fold higher in patients who experi-
enced more than one seizure before
randomization.
What does this mean for decision-
making? Clearly, little is lost in the
long run by deferring treatment in
patients who present with a first idio-
pathic seizure. Seizures are defined as
idiopathic when the patient has not
had significant previous head trauma
or a precipitating metabolic derange-
ment; has a normal neurologic exami-
nation; and, when appropriate, has a
normal result on a cerebral imaging
study. When immediate therapy is
undertaken, about 14 patients must be
treated to prevent one additional
patient from having a second seizure
within the next 2 years. Whether ther-
apy is immediate or deferred, the
patient should receive careful follow-
up evaluations at progressively longer
intervals over the first several years
after presentation. Although few pa-
tients in this study were treated with
newer anticonvulsants, none of the
currently available anticonvulsants are
universally effective; therefore, drug
selection is unlikely to result in out-
comes that differ from those described
in this large pragmatic trial.2,3
References
1. Marson A, Jacoby A, Johnson A, et al: Immediate
versus deferred antiepileptic drug treatment for early
epilepsy and single seizures: a randomized controlled
trial. Lancet 365:2007, 2005 [PMID 15950714]
2. French JA, Kanner AM, Bautista J, et al: Efficacy and
tolerability of the new antiepileptic drugs I: treatment of
new onset epilepsy. Report of the Therapeutics and Tech-
nology Assessment Subcommittee and Quality Standards
Subcommittee of the American Academy of Neurology
and the American Epilepsy Society. Neurology 62:1252,
2004 [PMID 15111659]
3. Wilby J, Kainth A, Hawkins N, et al: Clinical effective-
ness, tolerability and cost-effectiveness of newer drugs for
epilepsy in adults: a systematic review and economic eval-
uation. Health Technol Assess 9:15, 2005 [PMID
15842952]
jerrywolinsky@webmd.net
www.acpmedicine.com
Published by WebMD Inc.
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FOUNDING EDITOR: Daniel D. Federman, M.D.,
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www.acpmedicine.com
THIS MONTH’S UPDATES
continued from page 1
1. Mondillo S, Ballo P, Barbati R, et al: Effects of
simvastatin on walking performance and symptoms
of intermittent claudication in hypercholesterolemic
patients with peripheral vascular disease. Am J Med
114:359, 2003 [PMID 12714124]
2. Mohler ER 3rd, Hiatt WR, Creager MA: Choles-
terol reduction with atorvastatin improves walking
distance in patients with peripheral arterial disease.
Circulation 108:1481, 2003 [PMID 12952839]
3. Schillinger M, Exner M, Mlekusch W, et al:
Statin therapy improves cardiovascular outcome of
patients with peripheral artery disease. Eur Heart J
25:742, 2004 [PMID 15120884]
4. MRC/BHF Heart Protection Study of cholesterol
lowering with simvastatin in 20,536 high-risk indi-
viduals: a randomised placebo-controlled trial.
Lancet 360:7, 2002 [PMID 12114036]
The Future of Claudication
Treatment
ngiogenic growth factors, such as
A vascular endothelial growth factor
(VEGF) and basic fibroblast growth
factor (bFGF), are undergoing inten-
sive investigation for their potential
efficacy in patients with peripheral
arterial disease. These angiogenic fac-
tors may be delivered parenterally as
recombinant proteins or through gene
transfer using intra-arterial catheter
techniques or intramuscular injection.
Both VEGF and bFGF increase collat-
eral blood vessel development and
improve blood flow in experimental
models of hindlimb ischemia. The effi-
cacy of angiogenic growth factors in
patients with intermittent claudication
or critical limb ischemia is an active
area of investigation. Several placebo-
controlled trials in patients with claudi-
cation have been reported. In one trial,
intra-arterial infusion of recombinant
FGF-2 resulted in a significant increase
in peak walking time at 90 days.1 In
another study, intramuscular adminis-
tration of VEGF did not improve exer-
cise performance.2
Autologous implantation of bone
marrow mononuclear cells is a
promising area of study. These cells
have the potential to promote angio-
genesis, because they can supply
endothelial progenitor cells and they
secrete angiogenic factors.3
1. Lederman RJ, Mendelsohn FO, Anderson RD, et
al: Therapeutic angiogenesis with recombinant
fibroblast growth factor–2 for intermittent claudica-
tion (the TRAFFIC study): a randomised trial.
Lancet 359:2053, 2002 [PMID 12086757]
2. Rajagopalan S, Mohler ER 3rd, Lederman RJ, et
al: Regional angiogenesis with vascular endothelial
ACP Medicine 3
growth factor in peripheral arterial disease: a phase
II randomized, double-blind, controlled study of
No Role for Colchicine?
adenoviral delivery of vascular endothelial growth lthough small clinical trials have
factor 121 in patients with disabling intermittent
claudication. Circulation 108:1933, 2003 [PMID
14504183]
A shown improvement in survival
and reversal of cirrhosis with
3. Tateishi-Yuyama E, Matsubara H, Murohara T, colchicine treatment, a randomized,
et al: Therapeutic angiogenesis for patients with
limb ischaemia by autologous transplantation of
controlled trial found that in patients
bone-marrow cells: a pilot study and a randomised with advanced alcoholic cirrhosis,
controlled trial. Lancet 360:427, 2002 [PMID there was no reduction in overall or
12241713]
liver-specific mortality with colchi-
cine. Liver histology improved to sep-
Angioplasty in the Periphery tal fibrosis in a minority of pa-
evascularization procedures are tients after 24 months of treatment,
R indicated for patients with disabling
claudication, ischemic rest pain, or
but rates of improvement were similar
with placebo and colchicine.1
impending limb loss. Revasculariza- 1. Morgan TR, Weiss DG, Nemchausky B, et al:
tion can be achieved by catheter-based
Colchicine treatment of alcoholic cirrhosis: a ran-
domized, placebo-controlled clinical trial of patient
endovascular interventions. Percutane- survival. Gastroenterology 128:882, 2005 [PMID
ous transluminal angioplasty (PTA) of
iliac arteries has an initial success rate
15825072]
of 90%.1 Patency rates after 4 to 5 Slowing Progression in
years are approximately 60% to 80% Patients with Hepatitis
and are even higher with implantation
n patients with compensated cirrho-
of a stent. The success rate of PTA of
femoral and popliteal arteries is lower
Isis, specific therapies prevent the
development of clinical complications
than that of PTA of iliac arteries.
and therefore delay the need for liver
Patency rates at 1, 3, and 5 years are
transplantation. Treatment with pegy-
approximately 60%, 50%, and 45%,
lated interferon plus ribavirin should
respectively. The patency rate is better
be considered in patients with com-
when PTA is performed for relief of
pensated cirrhosis from hepatitis C
claudication rather than for limb sal-
virus infection, although the rate of
vage and is also better in patients with
sustained response is lower than in
good runoff (i.e., in patients with open
noncirrhotic patients.1 Moreover,
distal vessels). Stents have not been
antiviral treatment may worsen exist-
shown to improve the patency rates of
ing anemia or thrombocytopenia, and
femoral and popliteal arteries over
drug discontinuance is frequent. In
PTA alone. PTA of tibial and peroneal
patients with cirrhosis related to
arteries is associated with poorer out-
hepatitis B virus (HBV) infection,
come than PTA of more proximal
lamivudine appears to be a safe and
lesions and is usually performed in
effective antiviral agent that may
patients with critical limb ischemia
improve or stabilize liver disease in
who are considered at high risk for
selected patients with advanced cirrho-
vascular surgery. Limb salvage rates of
sis and active HBV replication.2
1 to 2 years range from 50% to 75%.
1. Wright TL: Treatment of patients with hepatitis
1. Kanani RS, Garasic JM: Lower extremity arterial occlu-
C and cirrhosis. Hepatology 36:S185, 2002 [PMID
sive disease: role of percutaneous revascularization. Curr
Treat Options Cardiovasc Med 7:99, 2005 [PMID
12407593]
15935118] 2. Lai CJ, Terrault NA: Antiviral therapy in patients
with chronic hepatitis B and cirrhosis. Gastroenterol
Clin North Am 33:629, 2004 [PMID 15324948]
4 GASTROENTEROLOGY
Who Are Candidates for Liver
IX Cirrhosis of the Liver Transplantation?
RAMÓN BATALLER, MD
rthotopic liver transplantation
O
PERE GINÈS, MD
(OLT) is a central tool for the man-
Liver Unit, Institut de Malalties
Digestives i Metabòliques, Hospital agement of advanced cirrhosis.1 In the
Clinic, Barcelona, Catalonia, Spain United States, more than 3,000 liver
4 What’s New in ACP Medicine • October 2005 www.acpmedicine.com

transplants are performed each year.
However, because there are many
more candidates for transplantation
than there are available donor livers,
the selection and timing of patient
referral are critical. The general indica-
tions for OLT are broadly categorized
as clinical and biochemical [see Table,
below].
Contraindications for OLT include
severe cardiovascular or pulmonary
disease, active drug or alcohol abuse,
malignancy outside the liver, sepsis, or
psychosocial problems that may jeop-
ardize a patient’s ability to follow
medical regimens after transplanta-
tion. The presence of HIV infection
was considered a contraindication to
transplantation, but successful liver
transplantations are now being per-
formed in patients in whom antiretro-
viral therapy has eliminated any
detectable HIV viral load. Additional
clinical study is required before OLT
can be offered routinely to such
patients.
In the United States, the Model for
End-Stage Liver Disease (MELD) is
the scoring system used by most liver
transplant centers for determining pri-
ority for OLT.2 MELD relies primarily
on the bilirubin level, international
normalized ratio, and creatinine level
to determine a patient’s risk of dying
within 3 months if OLT is not per-
formed. Patients’ scores are calculated
continuously while they are on the
waiting list for OLT. Scores typically
range from 6 (less ill) to 40 (gravely
ill). A MELD calculator is available on
the Internet (http://www.unos.org/
Indications for Liver Transplantation
resources/MeldPeldCalculator.asp?
index=98).
1. Brown KA: Liver transplantation. Curr Opin
Gastroenterol 21:331, 2005 [PMID 15818154]
2. Freeman RB Jr: MELD and liver allocation: con-
tinuous quality improvement. Hepatology 40:787,
2004 [PMID 15382164]
4 GASTROENTEROLOGY
XII Diverticulosis, Diverticulitis,
and Appendicitis
WILLIAM V. HARFORD, MD, FACP
University of Texas Southwestern
Medical Center at Dallas and Dallas
Veterans Affairs Medical Center
Preventing Diverticulitis
hanges in bacterial colonic microflo-
C ra have been reported in patients
with diverticulosis. It has been pro-
posed that these changes may lead to
low-grade chronic inflammation, pre-
disposing to the development of diver-
ticulitis. Long-term intermittent use of
oral rifaximin, a poorly absorbed
antibiotic, and mesalazine, an anti-
inflammatory agent, appears to reduce
the risk of diverticulitis in patients
with uncomplicated diverticulosis.1-4
1. Tursi A: Preventive therapy for complicated
diverticular disease of the colon: looking for a cor-
rect therapeutic approach. Gastroenterology
127:1865, 2004 [PMID 15578538]
2. Tursi A: Acute diverticulitis of the colon: current
medical therapeutic management. Expert Opin
Pharmacother 5:55, 2004 [PMID 14680435]
3. Latella G, Pimpo MT, Sottili S, et al: Rifaximin
improves symptoms of acquired uncomplicated
diverticular disease of the colon. Int J Colorectal
Dis 18:55, 2003 [PMID 12458383]
4. Tursi A, Brandimarte G, Daffina R: Long-term
treatment with mesalazine and rifaximin versus
rifaximin alone for patients with recurrent attacks
of acute diverticulitis of colon. Dig Liver Dis
34:510, 2002 [PMID 12236485]
Diagnosing Acute
Diverticulitis
he diagnosis of acute diverticulitis is
T often made on the basis of the histo-
ry and physical examination, which
includes abdominal, rectal, and pelvic
examinations; imaging studies are
used to confirm the diagnosis. Com-
puted tomography has become the
optimal method of investigation for
patients suspected of having divertic-
ulitis. The modified Hinchey classifica-
tion, which takes into account both
clinical and CT findings, is useful for
prognosis and management [see Table,
page 5].1
1. Kaiser AM, Jeng-Kae J, Lake JP, et al: The man-
agement of complicated diverticulitis and the role of
computed tomography. Am J Gastroenterol 100:910,
2005 [PMID 15784040]
Suspected Appendicitis? Don’t
Hold the Morphine
he abdominal examination is very
T important for the diagnosis of
appendicitis. This has led some physi-
cians to delay the administration of
narcotic analgesics until a surgeon has
had the opportunity to examine the
patient. It has been proven that this
practice is unnecessary: morphine does
not change the physical examination in
acute appendicitis, and early pain relief
does not affect the decision for surgery
in adults.1
1. Wolfe JM, Smithline HA, Phipen S, et al: Does
morphine change the physical examination in
patients with acute appendicitis? Am J Emerg Med
22:280, 2004 [PMID 15258869]

Disease Criteria 11 NEUROLOGY

Hepatocellular
Serum bilirubin > 3 mg/dl XIV Pain
liver disease Serum albumin < 2.5 g/dl
ALAN CARVER, MD
Prothrombin time > 5 sec above control
Mount Sinai School of Medicine
Serum bilirubin > 5 mg/dl
Cholestatic liver Intractable pruritus Keeping It Simple in Pain
disease Progressive bone disease
Recurrent bacterial cholangitis
Assessment
ain may be measured by use of a

Both hepatocellular
Recurrent or severe hepatic encephalopathy
Refractory ascites
P variety of scientifically validated
assessment tools. The Numeric Pain
and cholestatic liver Spontaneous bacterial peritonitis
disease Intensity Scale, in which the patient
Recurrent portal hypertensive bleeding
Progressive malnutrition
rates his or her pain on a scale from
zero to 10 (0 = no pain, 10 = worst
< 3 nodules pain imaginable), allows for quantifica-
Hepatocellular
No nodule > 5 cm
carcinoma tion of pain severity, evolution over
No portal invasion
time, and response to treatment. Use of
www.acpmedicine.com
the Visual Analog Scale or the Simple
Descriptive Pain Intensity Scale may be
better for some patient populations. In
the Visual Analog Scale, a mark on a
horizontal line denotes pain intensity;
in the Simple Descriptive Pain Intensity
Scale, the patient picks an appropriate
verbal pain descriptor. The Faces Pain
Scale for Adults and Children and the
Wong-Baker Faces Rating Scale consist
of multiple faces with various expres-
sions; the patient may select the facial
expression most consistent with his or
her current level of pain. This method-
ology has been validated for use in the
pediatric population. Several more
extensive tools for assessing pain and
its impact on the activities of daily liv-
ing, such as the Initial Pain Assessment
Tool, Brief Pain Inventory, McGill Pain
Questionnaire, Memorial Pain Assess-
ment Card, Neuropathic Pain Scale,
and Memorial Symptom Assessment
Scale, permit valid serial assessment of
pain and its functional import. For
general clinical practice, however, sim-
ple assessment tools are sufficient.
The Importance of Timely
Referral
any painful conditions may be
M managed adequately by a patient’s
primary care physician. However,
referral to a pain specialist or a team
approach may be best for certain cases
of chronic, cancer-related, or otherwise
complex pain that is debilitating or
refractory to treatment. Important
members of the pain management
team may include neurologists, psychi-
atrists, anesthesiologists, physiatrists,
physical or occupational therapists,
clergy, social workers, and counselors.
Pain clinics may bring all relevant team
members “under one roof.” Many
pain specialists believe that referrals
frequently are made past the so-called
golden hour when their intervention
may be of maximal effectiveness, espe-
cially in cases of neuropathic and can-
cer pain. Referral to a pain specialist
ideally should occur before significant
disability or loss of function occurs;
pain behaviors or the emergence of
maladaptive coping strategies may
serve as cues for referral.
Combination Therapy for
Neuropathic Pain
he role of opioids in neuropathic
T pain has been established since the
ACP Medicine 5
Modified Hinchey Classification
of Acute Diverticulitis
Stage Characteristic Symptoms
Mild clinical diverticulitis (left lower quadrant
0 abdominal pain, low-grade fever, leukocytosis,
no imaging information)
1a Confined pericolic inflammation, no abscess
Confined pericolic abscess (abscess or phlegmon
1b may be palpable; fever; severe, localized abdomi-
nal pain)
Pelvic, retroperitoneal, or distant intraperitoneal
2 abscess (abscess or phlegmon may be palpable,
fever, systemic toxicity)
3
Generalized purulent peritonitis, no communica-
tion with bowel lumen
Feculent peritonitis, open communication with
4
bowel lumen
Complications Fistula, obstruction (large bowel or small bowel)
late 1990s, when a series of well- Imaging Ankylosing
designed randomized, controlled
Spondylitis
clinical trials clearly demonstrated
adiologic evidence of sacroiliitis is
efficacy in neuropathic pain states
such as diabetic neuropathy. Current R essential in confirming a diagnosis
data suggest that neuropathic pain of ankylosing spondylitis. In patients
may be managed more effectively whose clinical presentation suggests
ankylosing spondylitis but whose
when morphine is combined with
gabapentin than when either agent is
used alone. Antiepileptic drugs
sacroiliac radiographs are normal, the
presence of HLA-B27 is highly sug-
gestive but not definitive evidence of
(AEDs) such as gabapentin, carba-
the disease. Follow-up studies of
mazepine, and topiramate may be patients in whom the diagnosis was
useful as adjuvant drugs in the treat- strongly suspected on the basis of the
ment of a variety of forms of neuro- clinical picture and HLA-B27 positivi-
pathic pain, including peripheral dia-
ty showed that sacroiliac joint abnor-
betic neuropathy, postherpetic neu- malities eventually appear on plain
ralgia, reflex sympathetic dystrophy,
x-rays, but the evolution may occur
trigeminal and glossopharyngeal over as many as 10 years. Magnetic
neuralgia, HIV neuropathy, and resonance imaging of the sacroiliac
spinal cord injury–related dysesthe- joints is a very sensitive method for
sias. These agents are also useful for detecting early sacroiliitis, as well as
postlaminectomy, phantom limb, inflammation elsewhere in the
and cancer pain. spine.
Although monotherapy (most
commonly with gabapentin) is often Tumor Necrosis Factor
tried initially in managing neuropath- Antagonists for Treating
ic pain, many patients are best served Spondyloarthritis
by a so-called cocktail approach that he tumor necrosis factor (TNF)
targets multiple mechanisms. T antagonists etanercept and inflix-
imab are approved for the treatment
of ankylosing spondylitis, as well as
15 RHEUMATOLOGY psoriatic arthritis. An increasing num-
ber of controlled and open-label stud-
III Seronegative Spondyloarthritis ies of the use of these agents in each of
FRANK C. ARNETT, MD, FACP the forms of spondyloarthritis have
University of Texas Health Science shown dramatic and rapid improve-
Center at Houston ment in symptoms; significantly
6 What’s New in ACP Medicine • October 2005
reduced inflammatory changes in the
spine and peripheral joints, as evi-
denced on MRI; and lowered acute-
phase reactants such as erythrocyte
sedimentation rate and C-reactive pro-
tein. Long-term efficacy and modifica-
tion of disease progression and out-
come have yet to be determined.1-3
Treatment with TNF-α antagonists
also has been shown to halt progres-
sion of secondary amyloidosis.4
Because of the high cost of these
agents and still-unanswered questions
about their long-term safety, guidelines
have been developed by international
consensus to facilitate the judicious
use of TNF antagonists.1 Many
patients with mild disease may never
require TNF antagonists.
1. Reveille JD, Arnett FC: Spondyloarthritis:
update on pathogenesis and management. Am J
Med 118:592, 2005 [PMID 15922688]
2. Gorman JD, Sack KE, Davis JC Jr: Treatment of
ankylosing spondylitis by inhibition of tumor
necrosis factor alpha. N Engl J Med 346:1349,
2002 [PMID 11986408]
3. Braun J, Brandt J, Listing J, et al: Treatment of
active ankylosing spondylitis with infliximab: a
randomised controlled multicentre trial. Lancet
359:1187, 2002 [PMID 11955536]
4. Fernandez-Nebro A, Tomero E, Ottiz-
Santamaria V, et al: Treatment of rheumatic
inflammatory disease in 25 patients with sec-
ondary amyloidosis using tumor necrosis factor
alpha antagonists. Am J Med 118:552, 2005
[PMID 15866260]
The Laboratory Picture of
Psoriatic Arthritis
aboratory testing in patients with
L psoriatic arthritis may show eleva-
tions in the erythrocyte sedimentation
rate or C-reactive protein level, anemia,
and hyperuricemia. Although symmet-
Coming in November
Clinical Essetials
VI Occupational Medicine
2 Dermatology
X Malignant Cutaneous Tumors
4 Gastroenterology
VI Gallstones and Biliary Tract Disease
7 Infectious Disease
XXXIX Infections Due to Mycobacteria
leprae and Nontuberculous Bacteria
13 Psychiatry
IX The Eating Disorders
14 Respiratory Medicine
IV Focal and Multifocal Lung Disease
16 Women’s Health
XXI Musculoskeletal Problems in the
Female Athlete
rical polyarthritis in these patients may
resemble rheumatoid arthritis, tests for
rheumatoid factor, antinuclear anti-
body, and antibodies to cyclic citrulli-
nated peptides (anti-CCP) should be
negative. Anti-CCP is a newly discov-
ered autoantibody marker for rheuma-
toid arthritis that is 65% sensitive and
96% specific. Synovial fluid shows
nonspecific inflammatory changes.
CLINICAL ESSENTIALS
I On Being a Physician
DAVID C. DALE, MD, FACP
University of Washington School of
Medicine
DANIEL D. FEDERMAN, MD, MACP
Harvard Medical School
Essential Skills
he physical examination remains a
T fundamental skill; the ability to rec-
ognize the difference between normal
and abnormal findings, adjusting for
age, sex, ethnicity, and other factors,
is crucial. Good record keeping is
essential—with regard to both a writ-
ten record and a mental record—so
that the circumstances of visits are
remembered and changes in a
patient’s appearance or other charac-
teristics that may not have been
recorded can be recognized. With
practice and attention, these skills—
history taking, physical examination,
and record keeping—can grow
throughout a professional lifetime.
Other aspects of care, such as select-
ing and performing diagnostic tests,
procedures, and treatments, require
evolving expertise. For all physicians,
it is necessary both to practice medi-
cine and to study regularly to main-
tain all of these essential skills.
Coping with Managed Care
he development of managed care in
T the United States has created a new
challenge for physicians: to serve as
advocates for their patients. In this
role, physicians are responsible for
overcoming organizational, geograph-
ic, and financial barriers to the provi-
sion of services that are important for
their patients. In organizations in
which guidelines for care have been
established, it may be necessary for a
physician to explain to administrators
the specific needs and problems of
www.acpmedicine.com
individual patients—sometimes over
and over again, because laypersons
may be less apt to recognize that
guidelines for clinical practice must
remain just guidelines. Because more
and more physicians are salaried and
are thus bound to the needs of popula-
tions of patients, physicians face the
problem of balancing the needs of
individual patients with the expecta-
tions of the employer. This is a delicate
and, in some places, even fragile bal-
ance. To serve both patients and the
employer well, a physician must devel-
op good judgment in managing patient
care under conditions in which the
allocation of resources is conservative.
CLINICAL ESSENTIALS
II Contemporary Ethical and
Social Issues in Medicine
CHRISTINE K. CASSEL, MD, MACP
University of Pennsylvania and
American Board of Internal Medicine
RUTH B. PURTILO, PHD
Creighton University Center for Health
Policy and Ethics
Values, Clarified
thical dilemmas must be clarified
E and presented clearly to all those
involved in the decision-making
process. For example, a spouse of an
incompetent patient who argues for
aggressive, clinically futile treatment
in the face of an imminently terminal
and untreatable illness can present the
physician with a conflict between
respecting the considered wishes of
family members and doing what the
physician judges is best for the
patient. Sometimes, enhanced com-
munication between physician,
patient, and family helps bring the
matter to resolution. For example,
having a discussion with the family
that is focused on the likelihood that
aggressive measures would only pro-
long the suffering of the patient may
convince them to end life-prolonging
interventions. In other circumstances,
however, the patient’s and family’s
beliefs may necessitate that the physi-
cian take aggressive measures to pre-
serve life at all costs. It may be impor-
tant to discuss the spiritual and moral
dimensions of the impending decision
explicitly. It is often helpful to involve
other physicians or nonphysician
mediators, such as the hospital ethi-
www.acpmedicine.com ACP Medicine 7

CDC Recommendation Report

Influenza Vaccine Preview 2005–2006
The Advisory Committee on Immunization Practices (ACIP) has issued an update to the past year’s recommendations
regarding the influenza vaccine

Vaccination of persons with conditions leading to compromise of the respiratory system

Vaccination against influenza is recommended for persons with any condition (e.g., cognitive dysfunction, spinal cord
injuries, seizure disorders, or other neuromuscular disorders) that can compromise respiratory function or the han-
dling of respiratory secretions.

Vaccination of health care workers

All health care workers should be vaccinated against influenza annually. Facilities that employ health care workers
should be strongly encouraged to provide vaccine to workers by using approaches that maximize immunization rates.

The role of live, attenuated influenza vaccine (LAIV) during vaccine shortages
Use of both available vaccines (i.e., both inactivated vaccine and LAIV) is encouraged for eligible persons every
influenza season, especially persons in recommended target groups. During periods when inactivated vaccine is in
short supply, the use of LAIV is especially encouraged when feasible for eligible persons (including health care work-
ers) because use of LAIV by these persons might considerably increase the availability of inactivated vaccine for per-
sons in groups at high risk.

The 2005–2006 strains

The 2005–06 trivalent vaccine virus strains are A/California/7/2004 (H3N2)–like, A/New Caledonia/20/99
(H1N1)–like, and B/Shanghai/361/2002-like antigens. For the A/California/7/2004 (H3N2)–like antigen, manufactur-
ers may use the antigenically equivalent A/New York/55/2004 virus, and for the B/Shanghai/361/2002-like antigen,
manufacturers may use the antigenically equivalent B/Jilin/20/2003 virus or B/Jiangsu/10/2003 virus.

Vaccine supply
The CDC and other agencies will assess the vaccine supply throughout the manufacturing period and will make rec-
ommendations preceding the 2005–06 influenza season regarding the need for tiered timing of vaccination of differ-
ent risk groups. In addition, the CDC will publish ACIP recommendations regarding inactivated vaccine subprioriti-
zation (tiering) on a later date.
Source:
Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep
54(early release):1, 2005
(http://www.cdc.gov/mmwr/preview/mmwrhtml/rr54e713a1.htm)

cists, patient advocates, social work-
ers, and clergy members, in the deci-
sion-making process.1 Once values are
explicitly discussed and differences
clarified, a plan may be agreed upon
by which all parties can abide.
1. DuVal G, Clarridge B, Gensler G, et al: A national sur-
vey of U.S. internists’ experiences with ethical dilemmas
and ethics consultation. J Gen Intern Med 19:251, 2004
[PMID 15009780]
Stem Cell Research
urrent research in genetics chal-
C lenges traditional assumptions of
the uniqueness of individual identity
and the acceptability of genetic inter-
ventions. Germline interventions were
considered completely ethically unac-
ceptable just a few years ago because
of the reluctance on the part of
geneticists to create changes that
would persist through subsequent
generations. However, research has
now progressed to the point of grow-
ing human stem cells under laborato-
ry conditions, and stem cell research
is thought to be one of the most
promising new areas for clinical inter-
ventions.1 Although the debate has
become intensely political and nation-
al funding of stem cell research by the
National Institutes of Health is strict-
ly proscribed, many in the scientific
community are actively supporting
stem cell research and are taking steps
to address some of the ethical con-
cerns raised by the use of these cells.
This shift has occurred in part
because stem cell techniques do not
create permanent germline changes.
Scientific research is ongoing, espe-
cially in other countries; in the United
States, interest in the clinical promise
of stem cell technology continues to
grow. Legislators in California and
Massachusetts have created and fund-
ed state-level research centers, and
other states are considering whether
to undertake similar initiatives.
1. Daar AS, Bhatt A, Court E, et al: Stem cell
research and transplantation: science leading ethics.
Transplant Proc 36:2504, 2004 [PMID 15561296]
12 ONCOLOGY
XVIII Head and Neck Cancer
EVERETT E. VOKES, MD, FACP
University of Chicago Pritzker School
of Medicine
Risks Held in Patients’ Hands
he primary risk factors for develop-
T ment of squamous cell carcinoma
 8 What’s New in ACP Medicine • October 2005 www.acpmedicine.com

(SCC) of the head and neck are the
use of tobacco and alcohol. Tobacco
use has clearly been demonstrated to
be an independent risk factor. The
likelihood of a malignancy increases
with the duration and extent of expo-
sure. Cigarette smoking, in particular,
is an important risk factor for laryn-
geal cancer. Cigar smoking has been
associated primarily with cancers of
the lip and oral cavity, presumably
because cigar smoke is not typically
inhaled. When inhaled, cigar smoke
places the smoker at risk for other
head and neck malignancies. There is
also concern about the use of smoke-
less tobacco as a risk factor for malig-
nancies of the oral cavity. After discon-
tinuance of the use of tobacco, the risk
of SCC of the head and neck diminish-
es gradually over time. Evidence, how-
ever, suggests that the risk does not
decline to the level associated with
persons who never smoked.1
Alcohol use is also associated with
SCC of the head and neck. By itself,
alcohol use is a smaller risk factor
than tobacco use and is of particular
importance for malignancies of the
oral cavity, oral pharynx, and
hypopharynx. However, the use of
alcohol and tobacco in combination
results in a multiplicative risk of SCC;
in persons who are both heavy smok-
ers and heavy drinkers, the risk of
SCC may be 200 times that of per-
sons who neither smoke nor drink.2
1. Pytynia KB, Grant JR, Etzel CJ, et al: Matched-
pair analysis of survival of never smokers and ever
smokers with squamous cell carcinoma of the head
and neck. J Clin Oncol 22:3981, 2004 [PMID
15459221]
2. Talamini R, Bosetti C, La Vecchia C, et al: Com-
bined effect of tobacco and alcohol on laryngeal can-
cer risk: a case-control study. Cancer Causes Control
13:957, 2002 [PMID 12588092]
Starting Off with
Chemotherapy
he administration of two or three
T cycles of chemotherapy before
surgery and radiotherapy, usually uti-
lizing cisplatin and fluorouracil, has
been shown to result in tumor shrink-
age in as many as 90% of patients
with head and neck cancers. Never-
theless, randomized trials have dem-
onstrated that overall survival rates
are not increased through the use of
induction chemotherapy, because local
and regional control is not better than
that achieved with surgery and radia-
tion alone. The addition of a taxane
to induction regimens has resulted in
high 2-year survival rates; however, a
meta-analysis of six trials could not
determine whether improved survival
rates were the result of the pharmaco-
logic effect of the taxane or that of
uncontrolled prognostic factors across
the various trials.1
Induction chemotherapy can be
considered a standard treatment
option for patients with locoregional-
ly advanced laryngeal or hypopharyn-
geal cancer. Until recently, induction
chemotherapy followed by radiation
therapy was the standard of care for
organ preservation2; however, the
findings of a large randomized multi-
center trial indicate that concomitant
chemoradiotherapy is superior to
induction chemotherapy for organ
preservation.3
1. Pignon JP, Syz N, Posner M, et al: Adjusting for pa-
tient selection suggests the addition of docetaxel to 5-flu-
orouracil-cisplatin induction therapy may offer survival
in squamous cell cancer of the head and neck. Anti-
cancer Drugs 15:331, 2004 [PMID 15057136]
2. Vokes EE, Stenson KM: Therapeutic options for la-
ryngeal cancer. N Engl J Med 349:2087, 2003 [PMID
14645634]
3. Forastiere AA, Goepfert H, Maor M, et al: Concur-
rent chemotherapy and radiotherapy for organ preserva-
tion in advanced laryngeal cancer. N Engl J Med
349:2091, 2003 [PMID 14645636]
Treating Salivary Gland Tumors
reatment of salivary gland tumors
T is predominantly surgical, which
leads to a proper definition of local
and regional tumor stage. Surgery
combined with radiotherapy, either
adjuvant or postoperative, appears to
increase survival.1,2 For unresectable
salivary gland tumors, neutron irradi-
ation can be used instead of conven-
tional radiotherapy. Chemotherapy is
reserved for patients with recurrent or
metastatic disease.
1. Terhaard CH, Lubsen H, Van der Tweel I, et al: Sali-
vary gland carcinoma: independent factors for locoregion-
al control, distant metastases, and overall survival: results
of the Dutch Head and Neck Oncology Cooperative
Group. Head Neck 26:681, 2004 [PMID 15287035]
2. Mendenhall WM, Morris CG, Amdur RJ, et al: Radio-
therapy alone or combined with surgery for salivary gland
carcinoma. Cancer 103:2544, 2005 [PMID 15880750]

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