NBME 26
1
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Exam Section 1: Item 2 of 50
National, Board of Medical Examiners
Comprehensive Basic Science Self-Assessment
2. Free purine and pyrimidine bases are reutilized in normal metabolism. In children
with Lesch-Nyhan syndrome who have intellectual disability, poor muscle
coordination, and self-mutilation tendencies, there is a defect in the salvage of which
of the following
pairs of bases?
A) Adenine and thymine
B) Guanine and hypoxanthine
C) Guanine and uric acid
D) Uracil and cytosine
E) Xanthine and hypoxanthine - ANS-B.
Lesch-Nyhan syndrome presents with intellectual disability, aggressive behavior,
self-mutilation, gout, and dystonia. The disorder is due to inactivating mutations of
hypoxanthine-guanine phosphoribosyltransferase (HGPRT), a key enzyme in the
purine salvage
pathway, and is inherited in an X-linked recessive fashion. HGPRT catalyzes the
conversion of guanine to guanosine monophosphate and hypoxanthine to inosine
monophosphate. Patients with deficient activity of HGPRT are unable to salvage
guanine and
hypoxanthine and develop resultant increased levels of xanthine and uric acid.
Hyperuricemia in Lesch-Nyhan syndrome is treated with xanthine oxidase inhibitors,
such as allopurinol or febuxostat, in order to reduce the synthesis of uric acid.
Incorrect Answers: A, C, D and E.
Adenine and thymine (Choice A) are purine and pyrimidine bases, respectively.
Purine and pyrimidine salvage are handled through two distinct pathways that are
not commonly involved in a single disease process.
Guanine and uric acid (Choice C) accumulation may occur as part of Lesch-Nyhan
syndrome, however, the accumulation of uric acid is also secondary to accumulation
of hypoxanthine. Choice B more accurately describes defective salvage of guanine
and
hypoxanthine as the fundamental effect of HGPRT dysfunction. The accumulation of
uric acid is secondary.
Uracil and cytosine (Choice D) are pyrimidine nucleotides. Pyrimidine salvage is not
affected by mutations of HGPRT.
Defects of xanthine and hypoxanthine (Choice E) metabolism may result from
defects in HGPRT. However, HGPRT dysfunction results in impaired hypoxanthine
,salvage with resultant excessive production of xanthine, rather than impaired
xanthine salvage.
Educational Objective: Lesch-Nyhan syndrome presents with intellectual disability,
aggressive behavior, self-mutilation, gout, and dyst
\10
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Exam Section 1: Item 11 of 50
National, Board of Medical Examiners
Comprehensive Basic Science Self-Assessment
11. An 8-year-old boy is brought to the physician by his parents because of
disruptive behavior. They say, "He is easily distracted, constantly interrupts us while
we are talking, and seems to be always moving. His teacher says he is always
talking with his
neighbors, has trouble completing tasks, and refuses to wait his turn when playing
games." Physical examination shows no abnormalities. If drug therapy is indicated,
administration of a drug with which of the following mechanisms of action is most
appropriate?
A) Antagonism at B-adrenergic receptors
B) Blockade of voltage-gated Na+ channels
C) Enhanced action of y-aminobutyric acid (GABA) at GABAA receptors
D) Increased release of dopamine and norepinephrine
E) Selective inhibition of uptake of serotonin at nerve terminals - ANS-D.
The first-line treatment for attention-deficit/hyperactivity disorder (ADHD) is stimulant
medication such as amphetamine salts, which increase presynaptic release of
dopamine and norepinephrine. ADHD presents with chronic symptoms of
hyperactivity/impulsivity
and/or inattention that occur in more than one setting and impair academic, social, or
emotional function. Children with predominant hyperactivity symptoms are unable to
sit still and may have difficulty taking turns (postulated to result from a dysregulated
reward
pathway), whereas children with predominant inattentive symptoms tend to
daydream, process information slowly, and demonstrate difficulty in completing tasks
(likely related to norepinephrine dysregulation). This patient is experiencing
symptoms of both
inattention and hyperactivity. Combination treatment with medications and
psychotherapy may be the most effective option, though medication monotherapy is
also appropriate for children older than 6 years. Stimulants, which include
amphetamine salts and
methylphenidate, are first-line agents. Both types of stimulants increase synaptic
dopamine and norepinephrine, which improve reward processing and attention,
respectively.
Incorrect Answers: A, B, C, and E.
Antagonism at ßB-adrenergic receptors (Choice A) is the mechanism of
B-adrenergic blocker medications. Some B-adrenergic blocker medications, such as
,propranolol, are centrally acting and can be used for performance anxiety or
traumatic brain injury-related
agitation. These medications are unhelpful in ADHD.
Blockade of voltage-gated Na" channels (Choice B) is the mechanism utilized by
several mood stabilizers and antiepileptics including carbamazepine and lamotrigine.
These medications are used for bipolar disorder, not ADHD.
Enhanced action of y-aminobutyric acid (GABA) at GABAA receptors (Choice
\100
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Exam Section 2: Item 50 of 50
Natjonal, Board pf Medical Examinersment
* 50. An 1814-g (4-lb) female newborn is delivered in the hospital at 24 weeks'
gestation to a 25-year-old primigravid woman via a spontaneous vaginal delivery.
Examination of the newborn shows no peripheral cyanosis. There is a grade 3/6,
continuous murmur
over the left midclavicular, second intercostal space. At the age of 2 days, the
newborn develops respiratory distress. Echocardiography shows a failure of a
vascular structure to close. The embryologic origin of this anomaly is most likely
which of the following
aortic arches?
O A) First
O B) Second
O C) Fourth
D) Fifth
O E) Sixth - ANS-E.
This patient has a moderate to large patent ductus arteriosus (PDA) as evidenced by
a continuous murmur and respiratory distress. In utero, oxygenated blood is obtained
from the placenta, not from the lungs, and the ductus arteriosus (DA) allows the
shunting of
oxygenated blood from the pulmonary
called a PDA, and if large enough, can lead to a profound left-to-right shunt, with
consequent heart failure, respiratory distress, and pulmonary hypertension. PDAS
that are small often go undetected until adulthood because the left-to-right shunt is
not significant
enough to cause symptoms. The DA arises from the sixth aortic arch, which also
gives rise to the proximal right pulmonary artery.
ectly to the aorta while bypassing the fetal lungs, which are filled with amniotic fluid.
At birth, closure of the DA occurs by the release of prostaglandins and increased
arterial oxygen tension. A DA that fails to close is
Incorrect Answers: A, B, C, and D.
First (Choice A) and second (Choice B) aortic arch structures include the maxillary
artery, a part of the external carotid artery, the ascending pharyngeal artery, and the
stapedial artery.
, Fourth (Choice C) aortic arch structures include the right subclavian artery and the
aortic arch from the origin of the left carotid artery to the beginning of the DA.
Fifth (Choice D) aortic arch structures regress and do not contribute to adult
cardiovascular structures.
Educational Objective: The sixth aortic arch gives rise to the ductus arteriosus, a
structure that allows shunting of placental oxygenated blood from the pulmonary
artery to the systemic circulation during development in utero but closes shortly after
birth. Persistence of
this structure is called a patent ductus arteriosus (PDA). Symptoms are dependent
upon the size of the PDA and the degree of left-to-right shunting, with
\101
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Exam Section 3: Item 1 of 50
Natjonal, Board of Medical Examinersent
* 1. The higher incidence of birth defects in children born to women more than 35
years old may be the result of environmental influences on chromosomes in
developmentally arrested oocytes at which of the following stages of cell division?
O A) Prophase, meiosis I
O B) Prophase, meiosis II
C) Metaphase, meiosis I
O D) Metaphase, meiosis II
E) Telophase, meiosis I - ANS-A.
In the normal development of the oocyte, women are born with a complement of
follicles that develop in utero and arrest in prophase of meiosis I. Upon reaching
menarche, some of the follicles mature during the menstrual cycle prior to being
released during
ovulation. In response to the hormonal stimulation from pituitary follicle-stimulating
hormone (FSH), the oocytes that may be ovulated advance from prophase of
meiosis I to metaphase of meiosis II. If fertilization occurs, the oocyte advances
through the remainder of
metaphase Il to completion. In prophase of meiosis I, the chromosomes remain
dormant in a paired tetrad (four total chromosomes: duplicated maternal and
paternal chromosomes). As meiosis I advances through metaphase, anaphase, and
telophase, the
recombined, crossed-over tetrads normally divide into two separate cells, where they
subsequently arrest in metaphase II. Normal progression through meiosis Il then
leads to a single haploid chromosome in each of the four daughter cells.
Nondisjunction during
prophase I results in the daughter cells receiving an uneven complement of
chromosomes. A nondisjunction event in meiosis I followed by a normal meiosis Il
results in four gametes, two of which lack a maternal or paternal chromosome, and
two of which contain
both a maternal and paternal chromosome. In the instance of normal separation in
meiosis I followed by a nondisjunction event of meiosis |l there are two
1
----------
Exam Section 1: Item 2 of 50
National, Board of Medical Examiners
Comprehensive Basic Science Self-Assessment
2. Free purine and pyrimidine bases are reutilized in normal metabolism. In children
with Lesch-Nyhan syndrome who have intellectual disability, poor muscle
coordination, and self-mutilation tendencies, there is a defect in the salvage of which
of the following
pairs of bases?
A) Adenine and thymine
B) Guanine and hypoxanthine
C) Guanine and uric acid
D) Uracil and cytosine
E) Xanthine and hypoxanthine - ANS-B.
Lesch-Nyhan syndrome presents with intellectual disability, aggressive behavior,
self-mutilation, gout, and dystonia. The disorder is due to inactivating mutations of
hypoxanthine-guanine phosphoribosyltransferase (HGPRT), a key enzyme in the
purine salvage
pathway, and is inherited in an X-linked recessive fashion. HGPRT catalyzes the
conversion of guanine to guanosine monophosphate and hypoxanthine to inosine
monophosphate. Patients with deficient activity of HGPRT are unable to salvage
guanine and
hypoxanthine and develop resultant increased levels of xanthine and uric acid.
Hyperuricemia in Lesch-Nyhan syndrome is treated with xanthine oxidase inhibitors,
such as allopurinol or febuxostat, in order to reduce the synthesis of uric acid.
Incorrect Answers: A, C, D and E.
Adenine and thymine (Choice A) are purine and pyrimidine bases, respectively.
Purine and pyrimidine salvage are handled through two distinct pathways that are
not commonly involved in a single disease process.
Guanine and uric acid (Choice C) accumulation may occur as part of Lesch-Nyhan
syndrome, however, the accumulation of uric acid is also secondary to accumulation
of hypoxanthine. Choice B more accurately describes defective salvage of guanine
and
hypoxanthine as the fundamental effect of HGPRT dysfunction. The accumulation of
uric acid is secondary.
Uracil and cytosine (Choice D) are pyrimidine nucleotides. Pyrimidine salvage is not
affected by mutations of HGPRT.
Defects of xanthine and hypoxanthine (Choice E) metabolism may result from
defects in HGPRT. However, HGPRT dysfunction results in impaired hypoxanthine
,salvage with resultant excessive production of xanthine, rather than impaired
xanthine salvage.
Educational Objective: Lesch-Nyhan syndrome presents with intellectual disability,
aggressive behavior, self-mutilation, gout, and dyst
\10
----------
Exam Section 1: Item 11 of 50
National, Board of Medical Examiners
Comprehensive Basic Science Self-Assessment
11. An 8-year-old boy is brought to the physician by his parents because of
disruptive behavior. They say, "He is easily distracted, constantly interrupts us while
we are talking, and seems to be always moving. His teacher says he is always
talking with his
neighbors, has trouble completing tasks, and refuses to wait his turn when playing
games." Physical examination shows no abnormalities. If drug therapy is indicated,
administration of a drug with which of the following mechanisms of action is most
appropriate?
A) Antagonism at B-adrenergic receptors
B) Blockade of voltage-gated Na+ channels
C) Enhanced action of y-aminobutyric acid (GABA) at GABAA receptors
D) Increased release of dopamine and norepinephrine
E) Selective inhibition of uptake of serotonin at nerve terminals - ANS-D.
The first-line treatment for attention-deficit/hyperactivity disorder (ADHD) is stimulant
medication such as amphetamine salts, which increase presynaptic release of
dopamine and norepinephrine. ADHD presents with chronic symptoms of
hyperactivity/impulsivity
and/or inattention that occur in more than one setting and impair academic, social, or
emotional function. Children with predominant hyperactivity symptoms are unable to
sit still and may have difficulty taking turns (postulated to result from a dysregulated
reward
pathway), whereas children with predominant inattentive symptoms tend to
daydream, process information slowly, and demonstrate difficulty in completing tasks
(likely related to norepinephrine dysregulation). This patient is experiencing
symptoms of both
inattention and hyperactivity. Combination treatment with medications and
psychotherapy may be the most effective option, though medication monotherapy is
also appropriate for children older than 6 years. Stimulants, which include
amphetamine salts and
methylphenidate, are first-line agents. Both types of stimulants increase synaptic
dopamine and norepinephrine, which improve reward processing and attention,
respectively.
Incorrect Answers: A, B, C, and E.
Antagonism at ßB-adrenergic receptors (Choice A) is the mechanism of
B-adrenergic blocker medications. Some B-adrenergic blocker medications, such as
,propranolol, are centrally acting and can be used for performance anxiety or
traumatic brain injury-related
agitation. These medications are unhelpful in ADHD.
Blockade of voltage-gated Na" channels (Choice B) is the mechanism utilized by
several mood stabilizers and antiepileptics including carbamazepine and lamotrigine.
These medications are used for bipolar disorder, not ADHD.
Enhanced action of y-aminobutyric acid (GABA) at GABAA receptors (Choice
\100
----------
Exam Section 2: Item 50 of 50
Natjonal, Board pf Medical Examinersment
* 50. An 1814-g (4-lb) female newborn is delivered in the hospital at 24 weeks'
gestation to a 25-year-old primigravid woman via a spontaneous vaginal delivery.
Examination of the newborn shows no peripheral cyanosis. There is a grade 3/6,
continuous murmur
over the left midclavicular, second intercostal space. At the age of 2 days, the
newborn develops respiratory distress. Echocardiography shows a failure of a
vascular structure to close. The embryologic origin of this anomaly is most likely
which of the following
aortic arches?
O A) First
O B) Second
O C) Fourth
D) Fifth
O E) Sixth - ANS-E.
This patient has a moderate to large patent ductus arteriosus (PDA) as evidenced by
a continuous murmur and respiratory distress. In utero, oxygenated blood is obtained
from the placenta, not from the lungs, and the ductus arteriosus (DA) allows the
shunting of
oxygenated blood from the pulmonary
called a PDA, and if large enough, can lead to a profound left-to-right shunt, with
consequent heart failure, respiratory distress, and pulmonary hypertension. PDAS
that are small often go undetected until adulthood because the left-to-right shunt is
not significant
enough to cause symptoms. The DA arises from the sixth aortic arch, which also
gives rise to the proximal right pulmonary artery.
ectly to the aorta while bypassing the fetal lungs, which are filled with amniotic fluid.
At birth, closure of the DA occurs by the release of prostaglandins and increased
arterial oxygen tension. A DA that fails to close is
Incorrect Answers: A, B, C, and D.
First (Choice A) and second (Choice B) aortic arch structures include the maxillary
artery, a part of the external carotid artery, the ascending pharyngeal artery, and the
stapedial artery.
, Fourth (Choice C) aortic arch structures include the right subclavian artery and the
aortic arch from the origin of the left carotid artery to the beginning of the DA.
Fifth (Choice D) aortic arch structures regress and do not contribute to adult
cardiovascular structures.
Educational Objective: The sixth aortic arch gives rise to the ductus arteriosus, a
structure that allows shunting of placental oxygenated blood from the pulmonary
artery to the systemic circulation during development in utero but closes shortly after
birth. Persistence of
this structure is called a patent ductus arteriosus (PDA). Symptoms are dependent
upon the size of the PDA and the degree of left-to-right shunting, with
\101
----------
Exam Section 3: Item 1 of 50
Natjonal, Board of Medical Examinersent
* 1. The higher incidence of birth defects in children born to women more than 35
years old may be the result of environmental influences on chromosomes in
developmentally arrested oocytes at which of the following stages of cell division?
O A) Prophase, meiosis I
O B) Prophase, meiosis II
C) Metaphase, meiosis I
O D) Metaphase, meiosis II
E) Telophase, meiosis I - ANS-A.
In the normal development of the oocyte, women are born with a complement of
follicles that develop in utero and arrest in prophase of meiosis I. Upon reaching
menarche, some of the follicles mature during the menstrual cycle prior to being
released during
ovulation. In response to the hormonal stimulation from pituitary follicle-stimulating
hormone (FSH), the oocytes that may be ovulated advance from prophase of
meiosis I to metaphase of meiosis II. If fertilization occurs, the oocyte advances
through the remainder of
metaphase Il to completion. In prophase of meiosis I, the chromosomes remain
dormant in a paired tetrad (four total chromosomes: duplicated maternal and
paternal chromosomes). As meiosis I advances through metaphase, anaphase, and
telophase, the
recombined, crossed-over tetrads normally divide into two separate cells, where they
subsequently arrest in metaphase II. Normal progression through meiosis Il then
leads to a single haploid chromosome in each of the four daughter cells.
Nondisjunction during
prophase I results in the daughter cells receiving an uneven complement of
chromosomes. A nondisjunction event in meiosis I followed by a normal meiosis Il
results in four gametes, two of which lack a maternal or paternal chromosome, and
two of which contain
both a maternal and paternal chromosome. In the instance of normal separation in
meiosis I followed by a nondisjunction event of meiosis |l there are two
