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  Contents copyright 1994, Mass. Medical Society.

Journal Watch summaries for May 24, 1994

PRENATAL STEROIDS PLUS SURFACTANT IMPROVE PREEMIE
OUTCOMES.
   Giving prenatal glucocorticoids to mothers with
threatened preterm delivery and giving surfactant to babies
with respiratory distress syndrome (RDS) have each been
shown to reduce the pulmonary and neurologic complications
of prematurity. This randomized, multicenter study indicates
that the two treatments together have an additive effect.
   Researchers randomized 157 pregnant women (24 to 32
weeks' gestation) with threatened preterm deliveries to
receive either dexamethasone (four 6-mg doses at 12-hour
intervals) or placebo. All preterm babies with RDS received
human surfactant after birth. Follow-up data were gathered
at 28 days and at 38 postconceptional weeks of age.
   The 79 babies of dexamethasone-treated mothers had
significantly less RDS than babies of placebo recipients.
They also required less surfactant, oxygen, and ventilatory
support, had a significantly lower incidence of
intraventricular hemorrhage or periventricular leukomalacia,
and had significantly more spontaneous closure of ductus
arteriosus. Most important, dexamethasone improved survival:
78 percent of infants whose mothers were treated, versus
only 53 percent of controls, survived without chronic
morbidity.
   Comment: Glucocorticoids appear to increase surfactant
synthesis and promote lung development, but how they reduce
neurologic complications is more speculative. The authors'
conclusion that prenatal steroids should be used in
threatened preterm deliveries together with rescue
surfactant after birth seems sound, since this strategy
increased survival without increasing morbidity.
--RA Dershewitz.
   Citation: Kari MA; et al. Prenatal dexamethasone treatment in
conjunction with rescue therapy of human surfactant: a randomized
placebo-controlled multicenter study. Pediatrics 1994 May;
93:730-6.

BARRIERS TO {*filter*}REHYDRATION THERAPY.
   {*filter*}rehydration therapy is effective against
vomiting, diarrhea, and dehydration in children and has been
endorsed by the American Academy of Pediatrics. Yet U.S.
pediatricians do not use it as recommended. This survey
helps explain why.
   Of 104 American pediatricians who completed the survey,
95 percent knew that {*filter*}rehydration is indicated for mild
dehydration and 97 percent reported using it for this
condition. But there were notable knowledge and practice
gaps regarding other guidelines: 42 percent of physicians
incorrectly thought that feeding should be withheld for at
least 24 hours after the onset of diarrhea, one third said
they did not use {*filter*}rehydration for moderate dehydration
or vomiting, and only 3 percent instructed parents to use a
syringe or spoon when rehydrating their child.
   Reasons for not following the guidelines included
financial disincentives (44 percent said that reimbur{*filter*}t
was better for IV than {*filter*}therapy), a lack of trained
staff to administer {*filter*}therapy (21 percent), staff
preference for IV therapy (13 percent), and inconvenience
(12 percent). Forty percent of respondents believed that
children refuse {*filter*}therapy because of the bitter taste,
and 11 percent believed that parents cannot provide adequate
{*filter*}rehydration at home.
   Comment: The physician's knowledge of recommended
guidelines is only one barrier to {*filter*}rehydration therapy.
This study presents us with still other barriers to be
tackled. --RA Dershewitz.
   Citation: Reis EC; et al. Barriers to use of {*filter*}rehydration
therapy. Pediatrics 1994 May; 93:708-11.

NICOTINE PATCHES APPEAR SAFE IN PATIENTS WITH CAD.
   Transdermal nicotine is an effective aid to smoking
cessation. However, nicotine may have adverse cardiovascular
effects. This double-blind trial evaluated the safety of
nicotine patches in 156 men and women with known coronary
artery disease who smoked at least one pack daily. Patients
with recent acute or unstable heart disease were excluded.
   Nicotine was begun at 14 mg per 24 hours and titrated to
21 mg after one week. At five weeks, 36 percent of patients
assigned to nicotine patches had quit smoking, versus 22
percent of those given placebo patches. The frequency of
angina, overall cardiac symptoms, and arrhythmias or
ischemia detected by 24-hour monitoring were similar in the
two groups. Only 3 of 77 patients with nicotine patches
withdrew because of side effects -- slightly fewer than in
the control group.
   Comment: Although larger studies with longer follow-up
are needed, these results suggest nicotine patches have no
major side effects in patients with stable CAD. --CD Mulrow.
   Citation: Working Group for the Study of Transdermal Nicotine
in Patients with Coronary Artery Disease. Nicotine replacement
therapy for patients with coronary artery disease. Arch Intern
Med 1994 May 9; 154:989-95.

DO GROWTH FACTORS BENEFIT PATIENTS ON CHEMOTHERAPY?.
   Bone-marrow toxicity is often the limiting factor in
chemotherapy. Two studies address the value of growth
factors in mitigating that toxicity.
   In the first study, 37 patients with a variety of tumors
(mostly {*filter*} cancer or non-Hodgkin's lymphoma) were
treated with intensive chemotherapy, autologous bone-marrow
transplantation, and infusion of peripheral-{*filter*} stem
cells. They were then randomized to receive infusions of
colony-stimulating factors (G-CSF and GM-CSF) or no growth
factors. The group given growth factors had a shorter
hospital stay than the control group (19 vs. 21 days) and
more quickly recovered an absolute neutrophil count of 1000
per microliter (12 vs. 21 days). However, the two groups had
similar durations of fever, numbers of documented septic
episodes, and transfusion requirements.
   A second study (not a randomized trial) compared two
groups of patients with newly diagnosed acute myelogenous
leukemia or myelodysplastic syndromes: 112 received G-CSF
and 85 received the same chemotherapeutic regimen but no G-
CSF. The patients' median age was 63 years, and many had a
poor prognosis at study entry. G-CSF accelerated recovery of
the neutrophil count but did not affect remission or
infection rates.
   Comment: Cost considerations make these kinds of studies
important. Comparison of clinically important end
points (as opposed to hematologic recovery) does not make it
clear when growth factors are most useful. The authors of
the first study speculate that the shortened hospital stay
in patients given growth factors did not reflect better
outcomes, but physicians' decisions to discharge patients
early based on recovery of neutrophil counts. --KI Marton.
   Citation: Spitzer G; et al. Randomized study of growth factors
post-peripheral-{*filter*} stem-cell transplant: neutrophil recovery
is improved with modest clinical benefit. J Clin Oncol 1994 Apr;
12:661-70.
   Citation: Estey E; et al. Use of granulocyte colony-
stimulating factor before, during, and after fludarabine plus
cytarabine induction therapy of newly diagnosed acute myelogenous
leukemia or myelodysplastic syndromes: comparison with
fludarabine plus cytarabine without granulocyte colony-
stimulating factor. J Clin Oncol 1994 Apr; 12:671-8.

APO E4 AND ALZHEIMER'S DISEASE: THE LINK GROWS
STRONGER.
   It has become clear that late-onset Alzheimer's
disease is strongly associated with apolipoprotein E4, one
of the three major forms of apolipoprotein E (see Journal
Watch accession number 940903001). A new study links apoE4
with early-onset Alzheimer's, in which memory or behavi{*filter*}
changes start at or before age 65.
   A Dutch population-based study identified all cases of
early-onset Alzheimer's disease in the Rotterdam area and
compared the frequency of the apoE4 gene in these cases with
that in non-demented controls. The risk for early-onset
Alzheimer's was much higher in people homozygous or
heterozygous for apoE4 (odds ratios, 8.1 and 2.3,
respectively) than in those with no apoE4 alleles. The risk
was particularly high if there was a family history of
dementia.
   A separate study in California identified a mechanism by
which apoE4 might cause disease. Rabbit neurons were
cultured in the presence of apoE3 and apoE4. The growth of
neurites (a indication of neuronal health) was increased by
apoE3 but decreased by apoE4.
   Comment: Although most previous studies have found a
strong association between apoE4 and late-onset Alzheimer's
disease (the most common kind), several reports have been
unable to document a link with early-onset disease. However,
these reports were smaller than this Dutch study and were
not population-based. Thus, apoE4 may play a central role in
all forms of Alzheimer's disease, and may do so by exerting
direct neurotoxic effects. --AL Komaroff.
   Citation: van Duijn CM; et al. Apolipoprotein E4 allele in a
population-based study of early-onset Alzheimer's disease. Nature
Genetics 1994 May; 7:74-8.
   Citation: Nathan BP; et al. Differential effects of
apolipoproteins E3 and E4 on neuronal growth in vitro. Science
1994 May 6; 264:850-2.

BLUNT TRAUMA IMPAIRS NEUTROPHIL CHEMOTAXIS IN
CHILDREN.
   Major blunt trauma increases the risk for infection in
{*filter*}s, in part because it impairs neutrophil (PMN)
chemotaxis. This study shows that blunt trauma also alters
PMN chemotaxis in children.
   Researchers studied 25 children and 25 {*filter*}s with major
blunt trauma and in 25 healthy {*filter*} controls. A standard
micropore filter assay measured PMN chemotaxis, and a new
fluorescent monoclonal antibody test determined PMN
maturity. All trauma victims, regardless of their age, had
similar PMN chemotactic values that were significantly lower
than those in controls. In addition, trauma victims had
significantly greater release of immature PMNs into the
circulation than controls. PMN chemotaxis was most depressed
during the first two days after the injury; it then
increased steadily and was normal by the ninth day.
   Comment: This study expands our knowledge of neutrophil
chemotaxis. However, other factors such as the disruption of
anatomic barriers contribute to the increased risk of
infection in victims of blunt trauma. These relationships
are complex and require further understanding.
--RA Dershewitz.
   Citation: Krause PJ; et al. Depressed neutrophil chemotaxis in
children suffering blunt trauma. Pediatrics 1994 May; 93:807-9.