available concerning management of patients who have
Samuel J. Mann, MD New York Presbyterian Hospital-Weill/Cornell Medical School,
a pheochromocytoma, fewer than two dozen papers deal
450 East 69th Street, New York, NY 10021, USA.
with the 98% who do not. Doctors and researchers simply
do not know how to manage these patients.
Current Hypertension Reports 2008, 10:12–18
This article presents a new understanding of the origin,
Current Medicine Group LLC ISSN 1522-6417
diagnosis, and successful treatment of otherwise unexplained
Copyright 2008 by Current Medicine Group LLC
paroxysmal hypertension, or pseudopheochromocytoma.
Paroxysmal hypertension always engenders a search for
a catecholamine-secreting pheochromocytoma. Yet 98%
The clinical presentation of pseudopheochromocytoma
of people with paroxysmal hypertension do not have this
has been reported [3,4••]. It is more common among
tumor. The cause and management of paroxysmal hyper-
women. The frequency of paroxysms ranges from daily to
tension remain a mystery, and the subject of remarkably
less than one per month, with paroxysms lasting from less
few papers. This review presents an approach to under-
than 10 minutes to a few days. Blood pressure levels can
standing and successfully treating this disorder. Patients
exceed 240/140 mm Hg. Hypertensive surges are typically
experience symptomatic blood pressure surges likely
accompanied by physical symptoms such as chest pain,
linked to sympathetic nervous system stimulation. A
light-headedness, headache, diaphoresis, nausea, palpita-
specific personality profile associated with this disorder
tions, dyspnea, and weakness. Most patients with severe
suggests a psychological basis, attributable to repressed
paroxysmal hypertension are hospitalized at some point
emotion related to prior emotional trauma or a repressive
and have some degree of impaired functioning [4••].
(nonemotional) coping style. Based on this understand-
The fear of recurrent attacks, which typically occur
ing, three forms of intervention, alone or in combination,
without warning, leads many patients to restrict their
appear successful: antihypertensive therapy with agents
activity and even leave their job. Thus, the disorder has a
directed at the sympathetically mediated blood pressure
considerable clinical and financial impact.
elevation (eg, combined α- and β-blockade or central
α-agonists such as clonidine); psychopharmacologic interventions including anxiolytic and/or antidepres-
sant agents; and psychological intervention, particularly
Many think of pseudopheochromocytoma as a diagnosis
reassurance and increased psychological awareness. An
by default after a pheochromocytoma has been excluded.
appropriately selected intervention can reduce or elimi-
Yet its specific characteristics (Table 1) enable the diag-
nosis to be made with considerable confidence. It is a disorder that is not found in just anyone. The following characteristics define the disorder.
IntroductionParoxysmal hypertension is the textbook symptom for a
1. Hypertensive paroxysms characterized by sudden
pheochromocytoma, but fewer than 2% of patients with
onset. Patients typically describe paroxysms as
this symptom actually have this tumor . This is not
having an abrupt onset unassociated with any
surprising, given the rarity of pheochromocytomas .
Typically, diagnostic evaluation reaches a dead end, leav-
2. Blood pressure elevation is associated with very
ing patients with an unexplained, difficult-to-treat, and
distressful physical symptoms. Blood pressure
elevation is not asymptomatic. Physical symptoms
The literature provides little guidance regarding
resemble pheochromocytomas, and include light-
clinical management. Although hundreds of papers are
headedness, headache, diaphoresis, nausea, chest
Severe Paroxysmal Hypertension Mann 13
encountered with pheochromocytoma. Although these
Table 1. Clinical features characteristic of pseudopheochromocytoma
high levels deserve attention, they do not merit an unend-ing search for a pheochromocytoma and rarely lead to a
1. Hypertensive paroxysms characterized by sudden onset
diagnosis of this tumor. If plasma norepinephrine is in the
2. Blood pressure elevation is associated with physical
range of 1000 to 2000 pg/mL, a clonidine suppression
symptoms (eg, headache, flushing, fatigue, dizziness)
test can be helpful, with a fall in norepinephrine level to
3. Episodes are not triggered by emotional distress or panic
the normal range suggesting that a pheochromocytoma is
4. Biochemical tests have been performed and do not
support the diagnosis of pheochromocytoma
Plasma metanephrine and normetanephrine levels
5. In nearly all cases, inquiry into psychosocial factors
have recently been reported to have high sensitivity and
reveals either a history of unusually severe abuse or
specificity in testing for a pheochromocytoma [7••].
trauma, or a defensive, very even-keeled personality style
Their plasma half-lives, which are much longer than those of catecholamines, may explain the greater sensi-
pain, palpitations, flushing, shortness of breath,
tivity. However, clinical experience indicates that mild
and weakness [4••,5]. Many patients feel like they
elevations are common, perhaps related to sympathetic
nervous system (SNS) stimulation in patients with parox-
3. Episodes are not triggered by emotional distress
ysmal hypertension, and should not provoke an endless
or panic. Unlike panic attacks, hypertensive
paroxysms are not heralded by panic. Instead,
It is often difficult for physicians to accept that a
patients typically insist that paroxysms occur “out
patient with paroxysmal hypertension does not have a
of the blue.” However, once an episode has begun,
pheochromocytoma, even if catecholamine levels are
the severe physical symptoms typically provoke a
normal. Rarely, catecholamine studies can be normal in
fear of dying, a classic symptom of the disorder.
a patient with a pheochromocytoma, but such cases rep-resent a very uncommon presentation of an uncommon
4. Biochemical tests do not support the diagnosis of
disorder. The likelihood of pseudopheochromocytoma is
a pheochromocytoma. Because of the similarities
much greater. The presence of the classic psychological
characteristics of pseudopheochromocytoma offers fur-
chromocytoma and because of the harm done if a
curable pheochromocytoma is missed, the possibility of a pheochromocytoma must be considered. This
Other common conditions
requires biochemical testing of blood or urine levels
The most common conditions resembling pseudopheo-
of catecholamines or catecholamine metabolites,
chromocytoma, and which need to be differentiated from
it, are panic disorder, labile hypertension, and posttrau-
5. In nearly all cases of severe paroxysmal hyperten-sion, inquiry into psychosocial factors reveals either a history of unusually severe abuse or trauma, or a defensive, very even-keeled personality style. A
Both panic disorder and pseudopheochromocytoma
distinct psychological profile is characteristic, and is
are characterized by sudden episodes of severely dis-
evident in nearly all patients with severe paroxysmal
tressing physical symptoms (eg, headache, dyspnea,
hypertension, as discussed below. This distinct
dizziness, weakness, and diaphoresis). The two differ
profile provides an important diagnostic clue and
in that attacks are dominated by the emotional mani-
enables a confident diagnosis of pseudopheochromo-
festation of panic in patients with panic disorder, but
cytoma, rather than a diagnosis by default.
not in those with pseudopheochromocytoma. In panic disorder, blood pressure elevation is usually milder (on average 20 mm Hg or less ), although some patients
experience considerable blood pressure elevation. In
contrast, pseudopheochromocytoma is dominated by
Excluding pheochromocytoma is the first order of busi-
the autonomic manifestation of a blood pressure surge
ness. If catecholamine studies are abnormal, radiologic (40–100 mm Hg or more [4••]), without panic. To a studies are needed. Radiologic imaging usually is not fair extent, the prominence of autonomic versus emo-indicated when catecholamine studies are normal, tional manifestations is reciprocally related in these particularly if plasma catecholamines were measured two disorders (Fig. 1). during, or urine catecholamines immediately following,
Hypertensive paroxysms can be viewed as the auto-
nomic equivalent of panic attacks, or panic attacks
Many patients have mildly elevated catecholamine without panic. This perspective led to consideration of
levels rather than the extremely high levels usually antidepressants as treatment.
14 Pathogenesis of Hypertension: Genetic and Environmental Factors
Labile hypertensionBlood pressure lability is common and should not be mis-construed as pseudopheochromocytoma, unless it has the
Panic attack Hypertensive
characteristics defined previously. In some patients, it is
asymptomatic, although others experience physical symp-toms such as hypertensive or tension headaches. Blood pressure increases can be associated with anxiety or hyperventilation . Unlike patients with pseudopheo-chromocytoma, most patients with labile essential hypertension readily attribute blood pressure fluctuation to stress and emotional distress.
Like pseudopheochromocytoma, posttraumatic stress dis-
order is associated with prior trauma. It is also associated with elevated plasma norepinephrine levels . However,
Figure 1. The reciprocal relationship between emotional and
in contrast to pseudopheochromocytoma, severe blood
autonomic manifestations in pseudopheochromocytoma and in
pressure elevation is not characteristic. Also, patients are
Current Hypertension Reports HR 10-1-1-01 fig. 1
very aware of the trauma and its impact.
Hypertensive paroxysms are often characterized by
Other medical conditions
one of two hemodynamic patterns. In some patients, par-
Many medical conditions, both common and rare, can oxysms are consistently characterized by palpitations and also cause paroxysmal hypertension, but seldom provide an increased heart rate. In others, the heart rate may be a diagnosis [4••]. Symptomatic hypertensive encepha-
unaffected, or even slowed, during paroxysms.
lopathy can usually be distinguished by a previous
The increased heart rate and plasma epinephrine level
history of sustained severe hypertension. Paroxysmal found in some patients with pseudopheochromocytoma hypertension can be a manifestation of other common resembles the syndrome of hyperdynamic circulatory state and uncommon conditions, such as a brain tumor, vari-
described by Frohlich et al. , and the primary hyper-
ous endocrine conditions, or coronary insufficiency, but epinephrinemia described by Streeten et al. . Neither usually other signs or symptoms typical of those disor-
group of investigators identified a cause for the increases
ders are evident; paroxysmal hypertension is unlikely to in heart rate and epinephrine level. be the sole manifestation.
The previously reported data of two patients
Illicit drugs (eg, cocaine or amphetamines) must be illustrate these patterns and reveal an important
considered, although patients with pseudopheochro-
underlying hormonal difference . In one case, the
mocytoma are so symptomatic and frightened that they blood pressure increased to 228/130 mm Hg during are unlikely to continue using, or to deny using, these a paroxysm, accompanied by cold extremities, reflex drugs. Ingestion of sympathomimetic agents, monoamine bradycardia, and a sixfold increase in plasma norepi-oxidase inhibitors, and tyramine or withdrawal from nephrine, with no increase in epinephrine level. In the clonidine should be evident from the history. Baroreceptor other case, the heart rate increased to 96 bpm with a failure is extremely unlikely without a predisposing con-
ninefold increase in epinephrine level, and no change in
dition, such as prior neck surgery or irradiation [12,13]. norepinephrine level. In addition, the abnormal blood pressure lability that it
The explanation for these differing hemodynamic
patterns can be found in differences in the pattern of SNS stimulation. The SNS is composed of two limbs, the adrenal and the neural. Stimulation of the adrenal
limb results in secretion of epinephrine by the adrenal
Sudden symptomatic blood pressure surges typical of gland, and an increased heart rate and cardiac output. pseudopheochromocytoma are more likely to be medi-
Stimulation of the neural limb results in increased neural
ated by the SNS, which is responsible for instantaneous release of norepinephrine from sympathetic nerve end-changes in blood pressure, than by volume or the renin-
ings in vascular smooth muscle, and increased peripheral
angiotensin system. Evidence of increased catecholamine resistance, without an increase in heart rate. levels during paroxysms support this notion . Kuchel
Different stressors can stimulate one limb of the SNS
et al.  also reported evidence of SNS activation in more than the other. For example, anxiety stimulates patients with paroxysmal hypertension, but were unable mainly the adrenal limb. The observed hemodynamic to identify the cause.
patterns of pseudopheochromocytoma suggest that in
Severe Paroxysmal Hypertension Mann 15
different patients, for reasons that remain unclear, one style. Two patterns of emotional unawareness appear to limb or the other can dominate.
be associated with pseudopheochromocytoma. The first pattern, seen in about two thirds of patients, consists of a history of severe trauma that most patients claim they
have put behind them, strikingly insisting they suffer no
The possibility that pseudopheochromocytoma’s origin and its underlying SNS activation are related to psycho-
logical factors is largely overlooked. This disregard is understandable because paroxysms are dominated by
A 33-year-old Hispanic man suffered from
hemodynamic changes and physical symptoms rather than
hypertensive paroxysms with blood pressure eleva-
by emotional distress, panic, or stressful circumstances.
tion as high as 220/140 mm Hg. He reported a
A breakthrough in understanding occurred with the
childhood history of severe physical abuse by his
observation that most patients acknowledged a history of
father. He insisted that he loved his father and bore
unusually severe abuse or trauma, often from as long ago as
no anger toward him. Treatment with alprazolam
childhood . Remarkably, most patients claimed they were
and amitriptyline eliminated hypertensive attacks.
free of lingering psychological effects, suggesting that they had repressed trauma-related emotions too overwhelming
A 35-year-old foreign-born woman who was
to be borne without adverse psychological consequences.
a physician experienced debilitating hypertensive
Patients had vivid memories of the trauma without the
paroxysms. She initially reported no prior history
powerful and painful emotions related to them.
of trauma. However, further questioning revealed
This observation suggested that the psychological origin
that, as a college student, she had been detained as
of pseudopheochromocytoma might involve emotions kept
a political prisoner for 30 days. She had been blind-
from awareness by defenses such as repression. Contrary to
folded, her life had been repeatedly threatened,
typical psychosomatic approaches, the absence rather than
and she had witnessed the death of several friends.
the presence of understandable emotional distress suggests
After she was freed, she moved on with her life. She
insisted there were no emotional aftereffects, had
Many trauma survivors experience severe emotion early,
not sought psychotherapy, and had discussed her
but eventually manage to repress trauma-related emotion
experiences with no one. Treatment with an anti-
and move forward. However, the repressed emotion has not
depressant eliminated the paroxysms.
It has been widely demonstrated that our emotions
In trauma survivors, it is important to recognize
affect blood pressure. Because we repress emotions that repression as a successful psychological defense rather can be far more overwhelming, it is plausible to suggest than as psychopathology. In handling overwhelming their role in otherwise unexplained SNS arousal and par-
emotion, the alternative to repression is long-term psy-
chological suffering and dysfunction. Many patients with
Repression is crucial to emotional health and explains pseudopheochromocytoma have dealt with major trauma
why some victims of severe trauma can survive without through repression, and have led lives marked by consid-apparent adverse psychological effects. They do not report erable achievement. Their resilience can be attributed to emotional distress, and usually do not even mention old their successful use of repression. trauma to a physician. The relationship between old
The second pattern of emotional unawareness, seen in
trauma and unexplained autonomic surges decades later about one third of patients, is the lifelong tendency to cope would never occur to either patient or doctor. Even psy-
unemotionally with the stresses of life . Such patients
chosocially conscious physicians do not ask about previous report never having experienced depression regardless of abuse or trauma, and instead focus on the patient’s report circumstances. They are doers, not reactors, and tend to of current stress and emotional distress.
be very even-keeled. Because they report little emotional
Unfortunately, the concept of repressed emotion is for-
distress, physicians rarely consider their condition as
eign to many. Therefore, most physicians and researchers linked to psychological factors. do not consider these concepts and their corollary treatment approaches, even though standard treatments have failed Clinical examplesand no other approaches have emerged.
A 66-year-old man suffered from hourlong epi-
Two patterns of emotional repression
sodes of blood pressure elevation to 190/110 mm Hg,
We cannot measure emotions that patients cannot report,
with diaphoresis and facial reddening. He did not
but the prominent use of repression can be surmised by
have a history of past trauma, but described himself
paying attention to a patient’s life story and personality
as very independent, never needing or seeking emo-
16 Pathogenesis of Hypertension: Genetic and Environmental Factors
tional support, and having a very even temperament
Table 2. Treatment options for paroxysmal
(the classic description of a repressor). He reported
having shed no tears 7 years earlier when his only son was left permanently paraplegic after a car acci-
1. Antihypertensive drug therapy
dent. Treatment with atenolol, terazosin, lorazepam,
a. Acute management of hypertensive paroxysms
i. IV labetalol or nitroprussideii. Clonidine
A 52-year-old pampered, well-to-do woman
experienced daily hypertensive attacks for 4 months.
She insisted she had no stress or distress, and that
she was very happy. However, after further discus-
2. Psychopharmacologic treatment
sion, she acknowledged to herself, for the first time,
a. Acute management of hypertensive paroxysms
that she was miserable and ashamed because she
had no job or purpose and felt useless. Her attacks ceased quickly as she became depressed for the first
time in her life. However, the awareness enabled her
i. Antidepressant agent (SSRI or tricyclic)
to initiate changes in her life. Her paroxysms ceased
3. Psychological interventions
In people with this pattern of not feeling, the absence
of emotion is usually a pattern developed in childhood.
They are not buffeted by emotions, and the experience of
depression or anxiety may be foreign to them.
*Interventions can be given alone or in combination.
IV—intravenous; SSRI—selective serotonin reuptake inhibitor.
Approach to TreatmentThe treatment of paroxysmal hypertension has been a (see below), given alone or in combination with an anti-major dilemma. Diuretics, angiotensin-converting enzyme hypertensive agent such as clonidine. inhibitors (ACEIs), and adrenergic receptor blockers (ARBs) do not prevent SNS-driven hypertensive surges, Preventive managementnor would they be expected to. The normal blood pressure As mentioned earlier, ACEIs, ARBs, and diuretics would between episodes precludes an aggressive antihypertensive not be expected to prevent paroxysms. Also, neither β-regimen. Although no controlled treatment trials have been blocker monotherapy nor α-blocker monotherapy reduces conducted, treatment approaches are needed. Based on the SNS-mediated blood pressure reactivity [18••]. However, understanding of pseudopheochromocytoma presented combined α- and β-blockade does, and offers a well-toler-in this review, certain approaches—whose validity is sug-
ated, logical approach [18••]. Clinical experience indicates
gested by their effectiveness in clinical practice—merit this approach can reduce peak blood pressure elevation. reporting (Table 2). Alone or in combination, they can Labetalol and carvedilol both provide combined α- and eliminate paroxysms in most patients and enable them to β-blockade, but both suffer from unpredictable bioavail-resume a normal life.
ability [17,19]. Therefore, an α-blocker (eg, doxazosin or terazosin) combined with a β-blocker would seem pref-
Antihypertensive drug therapy
erable. A central α-agonist such as clonidine is another
Acute management of hypertensive paroxysms
alternative, although its extended use is limited by side
The sudden and severe elevation of blood pressure dur-
ing paroxysms would seem to put patients at risk of an
If severe hypertensive paroxysms recur despite treat-
acute cerebrovascular or cardiovascular event. Fortu-
ment, dosage can be guided by the heart rate during
nately, such events seem rare, although more outcome paroxysms: if rapid, the β-blocker dose should be increased. data are needed.
If not rapid, it would be logical to instead increase the dose
Extreme blood pressure elevation can be treated with of the α-blocker. When given in combination with a β-
rapid-acting intravenous agents, such as labetalol or blocker, α-blockers such as doxazosin need not be titrated nitroprusside. With less severe elevation, an oral sympa-
higher than the 2- to 4-mg range for maximal effect .
tholytic agent, such as clonidine, can be given either in an emergency department or at home. Oral labetalol may Psychopharmacologic intervention be unreliable because of unpredictable bioavailability due Acute management of hypertensive paroxysms to first-pass hepatic metabolism . Milder paroxysms A rapid-acting benzodiazepine such as alprazolam can can be managed in some patients with an anxiolytic agent quickly abort attacks in some patients. It can be used
Severe Paroxysmal Hypertension Mann 17
instead of, or in combination with, an antihypertensive
Unfortunately, this shift in awareness usually is not
agent such as clonidine. The recently released orally achieved because most patients who are repressing over-disintegrating formulation of alprazolam can reduce whelming emotion related to unspeakable trauma need response time to a few minutes, allowing administration to continue repressing, and will defend against aware-of a second dose within 10 minutes in nonresponders.
ness. They are unlikely to be interested in, or to benefit from, psychotherapy aimed at awareness, and should not
be coerced into it. Psychotherapy could even do harm if
The use of antidepressant and anxiolytic agents to treat previously blocked overwhelming emotions are brought pseudopheochromocytoma was suggested by its similarity to awareness. The dictum that it is always best to deal to panic disorder. Antidepressant agents, including selective with the past is not inherently true. Patients who do not serotonin reuptake inhibitors and tricyclic antidepressants have a history of trauma but who have a lifelong tendency (TCAs), appear to prevent recurrence of paroxysms in to repress are also very resistant to psychotherapy. most patients at dosages recommended for treating panic
The wisest course would be to offer an explanation
disorder [3,4]. Improvement is evident within 2 weeks of for the disorder, and reassure the patient that the disorder instituting the effective dose. TCAs are associated with can be successfully managed and normal life resumed. If more side effects; however, agents such as desipramine are the patient comprehends and wishes to pursue psycho-better tolerated than older TCAs.
therapy, this course can be encouraged. If the patient
Antidepressant agents are effective even in patients cannot see the connection of the disorder with trauma or
who are unwilling to consider psychological factors. In repressed emotion, or prefers not to pursue psychother-such patients, it is important to emphasize the successful apy, psychological discussion and psychotherapy should track record of these drugs.
Although an antidepressant can prevent attacks, many
patients are reluctant to commit to long-term treatment with a psychotropic agent. A reasonable approach would be Obstacles to Successful Treatmentto start an antidepressant in patients with extremely severe Barriers are encountered with all three treatment hypertensive paroxysms (eg, > 220/120 mm Hg) or in those approaches. Barriers to treatment with antihypertensive with compromised ability to function. In others, acute agents include the ineffectiveness of ACEIs, ARBs, and management with alprazolam or clonidine, and/or mainte-
diuretics, and normal blood pressure levels between par-
nance therapy with combined α- and β-blockade, can be oxysms limiting the aggressiveness of antihypertensive tried first. Delaying initiation of antidepressant treatment therapy. In addition, antihypertensive agents are unlikely also allows for a trial of psychological intervention.
An antidepressant can be given in combination with
Barriers to treatment with antidepressants include
α- and β-blockade. If paroxysms have ceased, and the patients’ refusal to try them and, in some cases, multiple patient is otherwise normotensive, the α- and β-blocker drug intolerance that prevents using an effective dose. can be tapered and stopped, with careful follow-up.
Many patients refuse to try an antidepressant no matter how severely symptomatic they are because its use implies
a psychological cause. Some eventually agree to try one
because they are severely symptomatic and no other treat-
Extremely symptomatic hypertensive paroxysms can ment has helped. be terrifying to patients. The fear of dying during an
Finally, there are major barriers to psychological
attack can come to dominate their life. A physician’s intervention. Because pseudopheochromocytoma’s man-confident reassurance that the disorder can be treated, ifestations are physical rather than psychological and and that a catastrophic event or death during a par-
are not triggered by obvious current stressors, patients
oxysm is very unlikely can help reduce the terror and and doctors usually do not suspect its emotional basis. possibly the number and severity of attacks. Unfortu-
Many patients are extremely resistant to the concept
nately, most physicians—lacking understanding of the that emotions related to events from decades ago might disorder and experience treating it—cannot provide still be affecting them, particularly if they are not that reassurance.
experiencing distress. In addition, many patients are unknowingly battling to avoid psychological discus-
sion or awareness. Furthermore, for many patients, the
When the disorder’s origin in repressed emotion is barrier against conscious awareness of overwhelming explored with patients, some will grasp it at an emotional emotions must be maintained. level. With this awareness, some quickly experience
Sometimes, merely mentioning the emotional com-
a reduction or elimination of paroxysms without any ponent is so threatening at an unconscious level that the psychotherapy. Psychotherapy can then be helpful in pro-
patient might not return for follow-up care. Therefore, the
psychological origin must be broached very sensitively,
18 Pathogenesis of Hypertension: Genetic and Environmental Factors
and it is sometimes best to quickly abandon the topic if a 4.•• Mann SJ: Severe paroxysmal hypertension (pseudopheo- chromocytoma): understanding its cause and treatment. Arch Intern Med 1999, 159:670–674.
Clearly the treatment of pseudopheochromocytoma is This remains the only paper to offer an understanding of and treat-
a challenge and an art. Fortunately, successful treatment ment approach to pseudopheochromocytoma. is achievable in most cases, and a normal quality of life 5.
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origin and treatment have received remarkably little atten-
tion. Its obscure origin is attributable to its probable link 8.
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No potential conflict of interest relevant to this article was reported.
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18.•• Mann SJ: Neurogenic essential hypertension revisited: the case for increased clinical and research attention. Am J
Papers of particular interest, published recently,
Hypertens 2003, 16:881–888.
Presents the case for greater consideration of SNS-mediated hyperten-
sion, discusses clinical clues enabling its recognition, and discusses
the rationale for treatment with combined α/β-blockade. 19.
Morgan T: Clinical pharmacokinetics and pharma- codynamics of carvedilol. Clin Pharmacokinet 1994,
Pacak K, Linehan WM, Eisenhofer G, et al.: Recent 26:335–346. advances in genetics, diagnosis, localization, and treat-
Mann SJ, Gerber LM: Low dose alpha/beta blockade in the ment of pheochromocytoma. Ann Intern Med 2001, treatment of essential hypertension. 14:553–558.
Manger WM, Gifford RW, eds: Clinical and Experimen-tal Pheochromocytoma, edn 2. Malden, MA: Blackwell
Mann SJ: Severe paroxysmal hypertension. An autonomic syndrome and its relationship to repressed emotions. Psychosomatics 1996, 37:444–450.
Cerebral palsy (CP) has an incidence and prevalence rate ofabout two per 1000 in children (Grether et al.1992, Yeargin-Allsopp et al. 1992). Spasticity is a major clinical feature of over75% of cases of CP and is conventionally considered to be amajor cause of discomfort, gait abnormalities, and function-al limitations for persons with CP. Many resources have beendirected at the treatment of spa
( warfarin OR coumadin OR coumadine ) AND ( resistance OR drug resistance OR resist* ) AND ( review OR reviews ) (("warfarin"[MeSH Terms] OR "warfarin"[All Fields]) OR ("warfarin"[MeSH Terms] OR "warfarin"[All Fields] OR "coumadin"[All Fields]) OR ("warfarin"[MeSH Terms] OR "warfarin"[All Fields] OR "coumadine"[All Fields])