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abstract of
New England Journal of
Medicine
www.lib.hukm.ukm.my
Volume 359, Number 24 & 25- 11 & 18 Dec, 2008
UKM Medical Centre Library ©
NEJM - 359(24)&(25), 11 & 18 Dec, 2008 1
table of contents
ARTICLES
Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age.
Bejon, P., John Lusingu, Ally Olotu, Amanda Leach, Marc
Lievens, Johan Vekemans, Salum Mshamu, Trudie Lang,
Jayne Gould, Marie-Claude Dubois, Marie-Ange Demoitie,
Jean-Francois Stallaert, Preeti Vansadia, Terrell Carter,
Patricia Njuguna, Ken O. Awuondo, Anangisye Malabeja,
Omar Abdul, Samwel Gesase, Neema Mturi, Chris J.
Drakeley, Barbara Savarese, Tonya Villafana, W. Ripley
Ballou, Joe Cohen, Eleanor M. Riley, Martha M. Lemnge,
Kevin Marsh, and Lorenz von Seidlein.
Outbreak of adverse reactions associated with contaminated heparin.
Blossom, D.B., Alexander J. Kallen, Priti R. Patel, Alexis
Elward, Luke Robinson, Ganpan Gao, Robert Langer, Kiran
M. Perkins, Jennifer L. Jaeger, Katie M. Kurkjian, Marilyn
Jones, Sarah F. Schillie, Nadine Shehab, Daniel Ketterer,
Ganesh Venkataraman, Takashi Kei Kishimoto, Zachary
Shriver, Ann W. McMahon, K. Frank Austen, Steven
Kozlowski, Arjun Srinivasan, George Turabelidze, Carolyn
V. Gould, Matthew J. Arduino, and Ram Sasisekharan.
Thrombolysis during resuscitation for out-of-Hospital
Cardiac Arrest.
Bottiger, B.W., Hans-Richard Arntz, Douglas A. Chamberlain, Erich Bluhmki, Ann Belmans, Thierry Danays, Pierre A.
Carli, Jennifer A. Adgey, Christoph Bode, Volker Wenzel.
Effect of aspirin or r esistant starch on colorectal neoplasia in the lynch syndrome.
Burn, J., D. Timothy Bishop, Jukka-Pekka Mecklin, Finlay
Macrae, Gabriela Moslein, Sylviane Olschwang, Marie-Luise
Bisgaard, Raj Ramesar, Diana Eccles, Eamonn R. Maher,
Lucio Bertario, Heikki J. Jarvinen, Annika Lindblom, D.
Gareth Evans, Jan Lubinski, Patrick J. Morrison, Judy W.C.
Ho, Hans F.A. Vasen, Lucy Side, Huw J.W. Thomas, Rodney
J. Scott, Malcolm Dunlop, Gail Barker, Faye Elliott, Jeremy R.
Jass, Ricardo Fodde, Henry T. Lynch, and John C. Mathers.
An obesity-associated FTO gene variant and increased
energy intake in children.
Cecil, J.E., Roger Tavendale, Peter Watt, Marion M.
Hetherington, and Colin N.A. Palmer
A trial of combination antimalarial therapies in children
from Papua New Guinea.
Karunajeewa, H.A., Ivo Mueller, Michele Senn, Enmoore Lin,
Irwin Law, Servina Gomorrai, Olive Oa, Suzanne Griffin,
Kaye Kotab, Penias Suano, Nandao Tarongka, Alice Ura,
Dulcie Lautu, Madhu Page-Sharp, Rina Wong, Sam Salman,
Peter Siba, Kenneth F. Ilett, and Timothy M.E. Davis.
Dicer, drosha, and outcomes in patients with ovarian
cancer.
Merritt, W.M., Yvonne G. Lin, Liz Y. Han, Aparna A. Kamat,
Whitney A. Spannuth, Rosemarie Schmandt, Diana Urbauer,
Len A. Pennacchio, Jan-Fang Cheng, Alpa M. Nick, Michael
T. Deavers, Alexandra Mourad-Zeidan, Hua Wang, Peter
Mueller, Marc E. Lenburg, Joe W. Gray, Samuel Mok, Michael
J. Birrer, Gabriel Lopez-Berestein, Robert L. Coleman,
Menashe Bar-Eli, and Anil K. Sood.
Alfuzosin and symptoms of chronic prostatitis–chronic
pelvic pain syndrome.
Nickel, J.C., John N. Krieger, Mary McNaughton-Collins,
Rodney U. Anderson, Michel Pontari, Daniel A. Shoskes,
Mark S. Litwin, Richard B. Alexander, Paige C. White, Richard Berger, Robert Nadler, Michael O’Leary, Men Long
Liong, Scott Zeitlin, Shannon Chuai, J. Richard Landis,
John W. Kusek, Leroy M. Nyberg, Anthony J. Schaeffer.
Safety and immunogenicity of RTS,S/AS02D malaria
vaccine in infants.
Salim Abdulla, Rolf Oberholzer, Omar Juma, Sulende
Kubhoja, Francisca Machera, Christopher Membi, Said
Omari, Alwisa Urassa, Hassan Mshinda, Ajuza Jumanne,
Nahya Salim, Mwanjaa Shomari, Thomas Aebi, David M.
Schellenberg, Terrell Carter, Tonya Villafana, Marie-Ange
Demoitie, Marie-Claude Dubois, Amanda Leach, Marc
Lievens, Johan Vekemans, Joe Cohen, W. Ripley Ballou,
and Marcel Tanner.
CLINICAL PRACTICE
Prevention and treatment of seasonal influenza.
Glezen, W.P.
IMAGES IN CLINICAL MEDICINE
Subungual exostosis.
A. Campanelli and L. Borradori.
Bone destruction and regeneration in a patient with
breast cancer.
A. Malani and R. M. Abou-Jawde.
Periungual Tungiasis.
M. Muehlstaedt.
Postpartum venous thromboembolism.
R. Zalts and T. Hayek.
CASE RECORDS OF THE MASSACHUSETTES GENERAL
HOSPITAL
Case 39-2008: a 51- year-old woman with splenomegaly and anemia.
Abramson, J.S., Manjil Chatterji, and Aliyah Rahemtullah.
Case 38-2008 — A 58-Year-Old Man with Hemophilia, Hepatocellular Carcinoma, and Intractable
Bleeding.
Dzik, W.H., Michael Laposata, Martin Hertl, Warren S.
Sandberg, Manjil Chatterji, M.D., and Joseph Misdraji.
REVIEW ARTICLE
Medical progress: emporomandibular disorders.
Scrivani, S., David A. Keith, and Leonard B. Kaban.
NEJM - 359 (24)&(25), 11 & 18 Dec, 2008 2
ARTICLES
Bejon, P., John Lusingu, Ally Olotu, Amanda Leach,
Marc Lievens, Johan Vekemans, Salum
Mshamu, Trudie Lang, Jayne Gould, MarieClaude Dubois, Marie-Ange Demoitie, JeanFrancois Stallaert, Preeti Vansadia, Terrell
Carter, Patricia Njuguna, Ken O. Awuondo,
Anangisye Malabeja, Omar Abdul, Samwel
Gesase, Neema Mturi, Chris J. Drakeley,
Barbara Savarese, Tonya Villafana, W.
Ripley Ballou, Joe Cohen, Eleanor M. Riley,
Martha M. Lemnge, Kevin Marsh, and
Lorenz von Seidlein. (2008). Efficacy of
RTS,S/AS01E vaccine against malaria in
children 5 to 17 months of age. New En
gland Journal of Medicine, 359 (24), 24122415.
Plasmodium falciparum malaria is a pressing global health
problem. A previous study of the malaria vaccine RTS,S
(which targets the circumsporozoite protein), given
with an adjuvant system (AS02A), showed a 30%
rate of protection against clinical malaria in children 1
to 4 years of age. We evaluated the efficacy of RTS,S
given with a more immunogenic adjuvant system
(AS01E) in children 5 to 17 months of age, a target
population for vaccine licensure. RTS,S/AS01E shows
promise as a candidate malaria vaccine.
Blossom, D.B., Alexander J. Kallen, Priti R. Patel,
Alexis Elward, Luke Robinson, Ganpan Gao,
Robert Langer, Kiran M. Perkins, Jennifer L.
Jaeger, Katie M. Kurkjian, Marilyn Jones,
Sarah F. Schillie, Nadine Shehab, Daniel
Ketterer, Ganesh Venkataraman, Takashi
Kei Kishimoto, Zachary Shriver, Ann W.
McMahon, K. Frank Austen, Steven
Kozlowski, Arjun Srinivasan, George
Turabelidze, Carolyn V. Gould, Matthew J.
Arduino, and Ram Sasisekharan. (2008).
Outbreak of adverse reactions associated
with contaminated heparin. New England
Journal of Medicine, 359 (25), 2674-7684.
In January 2008, the Centers for Disease Control and
Prevention began a nationwide investigation of severe
adverse reactions that were first detected in a single
hemodialysis facility. Preliminary findings suggested that
heparin was a possible cause of the reactions. Heparin
contaminated with OSCS was epidemiologically linked
to adverse reactions in this nationwide outbreak. The
reported clinical features of many of the cases further
support the conclusion that contamination of heparin
with OSCS was the cause of the outbreak.
England Journal of Medicine, 359 (25),
2651-2662.
Approximately 70% of persons who have an out-ofhospital cardiac arrest have underlying acute
myocardial infarction or pulmonary embolism. Therefore,
thrombolysis during cardiopulmonary resuscitation may
improve survival. When tenecteplase was used without
adjunctive antithrombotic therapy during advanced
life support for out-of-hospital cardiac arrest, we did
not detect an improvement in outcome, in comparison
with placebo.
Burn, J., D. Timothy Bishop, Jukka-Pekka Mecklin,
Finlay Macrae, Gabriela Moslein, Sylviane
Olschwang, Marie-Luise Bisgaard, Raj
Ramesar, Diana Eccles, Eamonn R. Maher,
Lucio Bertario, Heikki J. Jarvinen, Annika
Lindblom, D. Gareth Evans, Jan Lubinski,
Patrick J. Morrison, Judy W.C. Ho, Hans F.A.
Vasen, Lucy Side, Huw J.W. Thomas,
Rodney J. Scott, Malcolm Dunlop, Gail
Barker, Faye Elliott, Jeremy R. Jass,
Ricardo Fodde, Henry T. Lynch, and John
C. Mathers. (2008). Effect of aspirin or
resistant starch on colorectal neoplasia in
the lynch syndrome. New England Journal
of Medicine, 359 (24), 2567-2578.
Observational and epidemiologic data indicate that the
use of aspirin reduces the risk of colorectal neoplasia;
however, the effects of aspirin in the Lynch syndrome
(hereditary nonpolyposis colon cancer) are not known.
Resistant starch has been associated with an
antineoplastic effect on the colon. The use of aspirin,
resistant starch, or both for up to 4 years has no
effect on the incidence of colorectal adenoma or
carcinoma among carriers of the Lynch syndrome.
Cecil, J.E., Roger Tavendale, Peter Watt, Marion
M. Hetherington, and Colin N.A. Palmer.
(2008). An obesity-associated FTO gene
variant and increased energy intake in
children. New England Journal of Medicine,
359 (24), 2558-2566.
Variation in the fat mass and obesity–associated (FTO)
gene has provided the most robust associations with
common obesity to date. However, the role of FTO
variants in modulating specific components of energy
balance is unknown. The FTO variant that confers a
predisposition to obesity does not appear to be involved
in the regulation of energy expenditure but may have
a role in the control of food intake and food choice,
suggesting a link to a hyperphagic phenotype or a
preference for energy-dense foods.
Bottiger, B.W., Hans-Richard Arntz, Douglas A.
Chamberlain, Erich Bluhmki, Ann Belmans,
Thierry Danays, Pierre A. Carli, Jennifer A.
Adgey, Christoph Bode, Volker Wenzel.
(2008). Thrombolysis during resuscitation
for out-of-Hospital Cardiac Arrest. New
NEJM - 359(24)&(25), 11 & 18 Dec, 2008 3
Karunajeewa, H.A., Ivo Mueller, Michele Senn,
Enmoore Lin, Irwin Law, Servina Gomorrai,
Olive Oa, Suzanne Griffin, Kaye Kotab,
Penias Suano, Nandao Tarongka, Alice Ura,
Dulcie Lautu, Madhu Page-Sharp, Rina
Wong, Sam Salman, Peter Siba, Kenneth F.
Ilett, and Timothy M.E. Davis. (2008). A trial
of combination antimalarial therapies in
children from Papua New Guinea. New
England Journal of Medicine, 359 (24),
2545-2557.
Malaria control is difficult where there is intense yearround transmission of multiple plasmodium species, such
as in Papua New Guinea. The most effective regimens
were artemether–lumefantrine against P. falciparum
and dihydroartemisinin–piperaquine against P. vivax.
The relatively high rate of treatment failure with
dihydroartemisinin–piperaquine against P. falciparum
may reflect cross-resistance between chloroquine and
piperaquine.
Merritt, W.M., Yvonne G. Lin, Liz Y. Han, Aparna
A. Kamat, Whitney A. Spannuth, Rosemarie
Schmandt, Diana Urbauer, Len A.
Pennacchio, Jan-Fang Cheng, Alpa M. Nick,
Michael T. Deavers, Alexandra MouradZeidan, Hua Wang, Peter Mueller, Marc E.
Lenburg, Joe W. Gray, Samuel Mok, Michael
J. Birrer, Gabriel Lopez-Berestein, Robert
L. Coleman, Menashe Bar-Eli, and Anil K.
Sood. (2008). Dicer, drosha, and outcomes
in patients with ovarian cancer. New
England Journal of Medicine, 359 (25),
2641-2650.
We studied Dicer and Drosha, components of the RNAinterference machinery, in ovarian cancer. Our findings
indicate that levels of Dicer and Drosha mRNA in
ovarian-cancer cells have associations with outcomes
in patients with ovarian cancer.
Nickel, J.C., John N. Krieger, Mary McNaughtonCollins, Rodney U. Anderson, Michel Pontari,
Daniel A. Shoskes, Mark S. Litwin, Richard
B. Alexander, Paige C. White, Richard
Berger, Robert Nadler, Michael O’Leary,
Men Long Liong, Scott Zeitlin, Shannon
Chuai, J. Richard Landis, John W. Kusek,
Leroy M. Nyberg, Anthony J. Schaeffer.
(2008). Alfuzosin and symptoms of chronic
prostatitis–chronic pelvic pain syndrome.
New England Journal of Medicine, 359 (25),
2663-2673.
In men with chronic prostatitis–chronic pelvic pain
syndrome, treatment with alpha-adrenergic receptor
blockers early in the course of the disorder has been
reported to be effective in some, but not all, relatively
small randomized trials. Our findings do not support
the use of alfuzosin to reduce the symptoms of chronic
prostatitis–chronic pelvic pain syndrome in men who
have not received prior treatment with an alpha-
blocker.
Salim Abdulla, Rolf Oberholzer, Omar Juma,
Sulende Kubhoja, Francisca Machera,
Christopher Membi, Said Omari, Alwisa
Urassa, Hassan Mshinda, Ajuza Jumanne,
Nahya Salim, Mwanjaa Shomari, Thomas
Aebi, David M. Schellenberg, Terrell Carter,
Tonya Villafana, Marie-Ange Demoitie,
Marie-Claude Dubois, Amanda Leach, Marc
Lievens, Johan Vekemans, Joe Cohen, W.
Ripley Ballou, and Marcel Tanner. (2008).
Safety and immunogenicity of RTS,S/AS02D
malaria vaccine in infants. New England
Journal of Medicine, 359 (24), 2533-2544.
The RTS,S/AS malaria vaccine is being developed for
delivery through the World Health Organization’s
Expanded Program on Immunization (EPI). We assessed
the feasibility of integrating RTS,S/AS02D into a
standard EPI schedule for infants. The use of the
RTS,S/AS02D vaccine in infants had a promising safety
profile, did not interfere with the immunologic responses
to coadministered EPI antigens, and reduced the
incidence of malaria infection.
CLINICAL PRACTICE
Glezen, W.P. (2008). Prevention and treatment
of seasonal influenza. New England Journal
of Medicine, 359 (24), 2579-2585.
This Journal feature begins with a case vignette
highlighting a common clinical problem. Evidence
supporting various strategies is then presented,
followed by a review of formal guidelines, when they
exist. The article ends with the author’s clinical
recommendations. In February 2007, fever developed
in a previously healthy 15-year-old girl, with a peak
temperature of 102°F (38.9°C) and mild upper
respiratory congestion. The next day she was seen
by her primary care physician. A rapid screening test
for group A streptococcus was negative, and
oseltamivir was prescribed. After two doses, she
continued to have fever and also had nausea and
emesis, . . .
IMAGES IN CLINICAL MEDICINE
A. Campanelli and L. Borradori. (2008). Subungual
exostosis. New England Journal of
Medicine, 359 (25), e31.
A 12-year-old girl with an unremarkable history was
evaluated for a nodule of the lateral nail fold on the
right hallux that had been present for 3 months (Panel
A). The lesion, which was initially believed to be a
wart, was treated with a topical salicylic acid
preparation, with no improvement. The nodule
measured 10 mm in diameter, and the distal nail plate
showed onycholysis and had been destroyed. A
radiograph revealed a calcifying projection on the
dorsolateral part of the distal phalanx, continuous with
NEJM - 359 (24)&(25), 11 & 18 Dec, 2008 4
the underlying bone (Panel B), the features of which
were consistent with a subungual exostosis. . . .
CASE RECORDS OF THE MASSACHUSETTES
GENERAL HOSPITAL
A. Malani and R. M. Abou-Jawde. (2008). Bone
destruction and regeneration in a patient
with breast cancer. New England Journal
of Medicine, 359 (24), 2586.
A 58-year-old woman presented with a cavitating left
breast lesion and increasing pain in the left arm. For
over a year she had noticed an enlarging breast mass
but did not seek medical advice. Imaging showed
metastatic disease in the chest and brain. Serum
calcium and alkaline phosphatase levels were within
the normal range. Since she had a marked decrease in
function of her left arm, a plain radiograph was
obtained. The image disclosed a destructive process
involving the proximal humerus, with multiple pathologic
fractures, presumably due to bony metastatic disease
(Panel A). Palliative left total mastectomy was
performed. The . . .
Abramson, J.S., Manjil Chatterji, and Aliyah
Rahemtullah. (2008). Case 39-2008: a 51year-old woman with splenomegaly and
anemia. New England Journal of Medicine,
359 (25), 2707-2718.
Dr. Jeffrey A. Barnes (Hematology–Oncology): A 51year-old woman was admitted to this hospital because
of anemia and splenomegaly. The patient was in her
usual state of health until approximately 2 months
before admission, when fatigue developed, followed
by night sweats, left-upper-quadrant fullness, early
satiety, edema of the legs, and dyspnea on exertion.
Furosemide was prescribed, but symptoms persisted.
One month before admission, she was admitted to
another hospital. On examination, the spleen extended
to the pelvic brim and the legs were edematous. A
direct Coombs’ test was negative for IgG and
complement. Other laboratory-test results are shown
in Table 1. . .
M. Muehlstaedt. (2008). Periungual Tungiasis.
New England Journal of Medicine, 359
(24),e30.
A healthy 35-year-old man presented with small eggs
and a brownish lesion on the medial edge of his right
big toe (Panel A). Two weeks before presentation, he
had returned from a holiday trip to Brazil, where he
had been barefoot. The patient was afebrile and without
malaise. The brownish part (the decomposing adult
sand flea) was excised, and multiple eggs appeared
after the application of lateral pressure (Panel B). After
disinfection, a sterile dressing was applied. The patient
had a complete recovery with no additional symptoms.
Tungiasis is an ectoparasitosis in which the fertilized
female sand flea . . .
R. Zalts and T. Hayek. (2008). Postpartum venous
thromboembolism. New England Journal of
Medicine, 359 (25), 2706.
A previously healthy 34-year-old woman, gravida 7,
para 5, presented on postpartum day 14 with severe
low back pain, chest pain, dyspnea, and substantial
swelling of both legs after an uneventful cesarean
section, performed with combined spinal–epidural
anesthesia. During that period she was bedridden.
Examination of the pelvis and legs with Doppler
ultrasonography revealed bilateral deep venous
thrombosis extending to the iliac veins. A computed
tomographic (CT) scan of the abdomen and pelvis
showed the thrombus extending through the inferior
vena cava and both ovarian veins (Panel A,
arrowheads). A CT scan of the chest showed
pulmonary embolism in the . . .
Dzik, W.H., Michael Laposata, Martin Hertl, Warren
S. Sandberg, Manjil Chatterji, M.D., and
Joseph Misdraji. (2008). Case 38-2008 —
A 58-Year-Old Man with Hemophilia,
Hepatocellular Carcinoma, and Intractable
Bleeding. New England Journal of Medicine,
359 (24), 2587-2597.
Dr. Abner Louissaint (Pathology): A 58-year-old man
with hemophilia was admitted to this hospital because
of hepatitis C infection, hepatocellular carcinoma, and
recurrent bleeding. A diagnosis of hemophilia A (factor
VIII deficiency) had been made in infancy. The
hemophilia was manifested by multiple hemarthroses,
was treated with multiple transfusions of blood
products and clotting factors, and was complicated
by hepatitis C infection (genotype 1a). Two years
before admission, a liver biopsy revealed chronic
hepatitis with a score of 3 for portal activity and a
score of 2 for lobular activity, with bridging . . .
REVIEW ARTICLE
Scrivani, S., David A. Keith, and Leonard B. Kaban.
(2008).
Medical
progress:
emporomandibular disorders. New England
Journal of Medicine, 359 (25), 2693-2705.
The temporomandibular joint (TMJ) may be affected
by inflammatory, traumatic, infectious, congenital,
developmental, and neoplastic diseases, as seen in
other joints. However, the most common affliction of
the TMJ and masticatory apparatus is a group of
functional disorders with associated pain that occurs
predominantly in women and was previously known as
the TMJ pain dysfunction syndrome. Since 1978, there
have been substantial changes in the study of etiologic
factors, pathophysiology, diagnosis, and management
of what are now called temporomandibular disorders.
NEJM - 359(24)&(25), 11 & 18 Dec, 2008 5
NEJM - 359 (24)&(25), 11 & 18 Dec, 2008 6
NEJM - 359(24)&(25), 11 & 18 Dec, 2008 7
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