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  Contents copyright 1994, Mass. Medical Society.

Journal Watch Summaries for July 22, 1994

DOES FIBROADENOMA CONFER A HIGHER {*filter*}-CANCER RISK?.
  N Engl J Med 1994 Jul 7; 331:10-5.

LV HYPERTROPHY IS A MARKER FOR STROKE RISK.
  JAMA 1994 Jul 6; 272:33-6.

LEGIONNAIRES' DISEASE FROM COOLING TOWERS.
  MMWR 1994 Jul 15; 43:491-3,499.

PERTUSSIS MAKES A COMEBACK IN THE U.S..
  N Engl J Med 1994 Jul 7; 331:16-21.

DOES ACYCLOVIR PROLONG LIFE IN HIV-INFECTED PATIENTS?.
  Ann Intern Med 1994 Jul 15; 121:100-8.

INVASIVE BACTERIAL INFECTIONS IN HIV-POSITIVE
CHILDREN.
  J Pediatr 1994 Jun; 124:846-52.

PROGRESS TOWARD POLIO ERADICATION.
  MMWR 1994 Jul 15; 43:499-503.

FLUVASTATIN FOR HYPERCHOLESTEROLEMIA.
  Am J Cardiol 1994 Jul 15; 74:149-54.

DOES FIBROADENOMA CONFER A HIGHER {*filter*}-CANCER RISK?.
   There is controversy over whether fibroadenomas --
benign {*filter*} tumors commonly found in young women -- mark
an increased risk for subsequent {*filter*} cancer. This study
compared {*filter*}-cancer rates in three groups: 1835 women
with fibroadenoma, a control group of 1640 sisters-in-law of
these women, and the general population of Connecticut.
   Overall, during a mean follow-up period of about 23
years, the women with fibroadenoma had approximately double
the rate of {*filter*} cancer as compared with both control
groups. However, this risk varied among subgroups of
fibroadenoma patients. In women whose fibroadenomas had
"complex" histology or who had adjacent tissue with
proliferative disease, the risk of {*filter*} cancer was more
than doubled compared to the population controls and more
than tripled compared to the sister-in-law controls. A
family history of {*filter*} cancer appeared to augment these
risks. In contrast, the roughly two-thirds of fibroadenoma
patients with neither complex histology nor {*filter*} cancer in
the family did not have an increased risk for {*filter*} cancer.
   Comment: A minority of women with fibroadenoma may be at
increased risk for {*filter*} cancer. Whether those women would
benefit from early mammographic surveillance, as some have
proposed, is unknown. --AS Brett.
   Citation: Dupont WD; et al. Long-term risk of {*filter*} cancer in
women with fibroadenoma. N Engl J Med 1994 Jul 7; 331:10-5.

LV HYPERTROPHY IS A MARKER FOR STROKE RISK.
   Left-ventricular hypertrophy is a common complication
of hypertension. Although hypertension is an important risk
factor for stroke, whether LV mass predicts stroke
independently has been uncertain. This study evaluated the
relation between stroke and LV mass in 1230 elderly people
enrolled in the Framingham Heart Study.
   All subjects were free of cerebrovascular disease and
atrial fibrillation on examination in 1979-81. During eight
years of follow-up, 62 had strokes and 27 had TIAs. Subjects
were grouped into quartiles based on the ratio of LV mass
(estimated by echocardiography) to height. In men, the risk
for a cerebrovascular event varied from 5 percent in the
lowest quartile to 18 percent in the highest. In women, the
corresponding risks ranged from 3 to 12 percent. In a
multivariate analysis, the risk for cerebrovascular events
rose by 45 percent with each quartile increment in LV-mass-
to-height ratio, even after adjustment for {*filter*} pressure,
age, sex, and other stroke risk factors.
   Comment: One possible explanation for the correlation
between LV mass and stroke is that LV mass reflects long-
term {*filter*} pressure better than the occasional outpatient BP
measurements for which this analysis controlled. These
findings suggest that efforts to control hypertension should
be especially vigorous in patients with LV hypertrophy.
--TH Lee.
   Citation: Bikkina M; et al. Left ventricular mass and risk of
stroke in an elderly cohort: the Framingham Heart Study. JAMA
1994 Jul 6; 272:33-6.

LEGIONNAIRES' DISEASE FROM COOLING TOWERS.
   Some 1000 to 1300 cases of Legionnaires' disease are
reported annually to the CDC, accounting for 1 to 5 percent
of community-acquired pneumonias in {*filter*}s. The disease is
probably underdiagnosed due to a low index of suspicion.
This report describes three outbreaks of Legionnaires'
disease linked to aerosol emissions from cooling towers.
   In the summer and fall of 1993, there were 11 cases, 3 of
them fatal, in Fall River, Mass.; 17 cases, 1 fatal, in a
state prison in Michigan; and 17 cases, 2 fatal, in eastern
Rhode Island. In all three outbreaks, epidemiologic
investigation and cultures for Legionella pneumophila
indicated that the source was a nearby cooling tower. No
further cases developed after the towers were
decontaminated.
   Comment: Although L. pneumophila can be cultured from up
to 40 percent of cooling towers and can be spread by other
aerosolizing devices (such as humidifiers and decorative
fountains), outbreaks are rare. Nevertheless, alert
clinicians should consider the possibility of Legionnaires'
disease when they encounter cases of community-acquired
pneumonia. Urinary antigen testing is a rapid, fairly
sensitive, and highly specific means of detecting the
L. pneumophila serotype that causes most of the cases.
--DM Berwick.
   Citation: Legionnaires' disease associated with cooling
towers -- Massachusetts, Michigan, and Rhode Island, 1993. MMWR
1994 Jul 15; 43:491-3,499.

PERTUSSIS MAKES A COMEBACK IN THE U.S..
   Over 6000 cases of pertussis were reported in the U.S.
in 1993, the highest number in 25 years. This report
describes one outbreak of 352 cases in Cincinnati, Ohio.
   The median age of the affected patients was higher than
that in the previous 14 years (17 months vs. 6 months); 22
percent of cases were in patients more than five years old,
and 11 percent were in patients over 12. Of the children
whose immunization history was known, 70 to 80 percent had
received an appropriate series of DPT vaccinations before
their illness. About a third of patients (primarily infants
in their first year) were hospitalized; one required brief
mechanical ventilation, and none died. The authors describe
their efforts to contain the epidemic through surveillance,
education of physicians and the community, an accelerated
DPT immunization schedule for infants, and liberal use of
prophylactic antibiotics in patients and their contacts when
cases were suspected.
   Comment: The reasons for this outbreak are unclear.
Perhaps its most interesting and worrisome feature is that
most of those affected were properly vaccinated children.
Ongoing examination of the efficacy of pertussis
immunization is obviously in order. --AS Brett.
   Citation: Christie CDC; et al. The 1993 epidemic of pertussis
in Cincinnati: resurgence of disease in a highly immunized
population of children. N Engl J Med 1994 Jul 7; 331:16-21.

DOES ACYCLOVIR PROLONG LIFE IN HIV-INFECTED PATIENTS?.
   Preliminary results from several trials suggest that
adding acyclovir to zidovudine therapy might prolong
survival of HIV-infected patients. This observational study
adds to that evidence.
   Of 786 HIV-positive men who began taking zidovudine
before being diagnosed with AIDS, nearly two-thirds
subsequently used acyclovir, either as anti-HIV therapy or
for other conditions. Although acyclovir use did not prevent
cytomegalovirus infection or progression to AIDS, the
combination of acyclovir and zidovudine was associated with
significantly better survival. For example, two-year
survival rates after developing AIDS or reaching a CD4 count
of 50 cells/microliter were 70 percent in men who were using
or had used acyclovir and 31 percent in those who never took
acyclovir. The median survival times for these two groups
were 1018 and 544 days, respectively. Longer survival was
associated with longer continuous use of acyclovir, but not
with the daily dose of acyclovir.
   Comment: Do these findings reflect some sort of synergism
between acyclovir and zidovudine, or merely biases
introduced by confounding factors that are inherent in
observational studies? Regardless of the explanation, a
randomized trial is needed to confirm a true life-prolonging
effect of acyclovir. --AS Brett.
   Citation: Stein DS; et al. The effect of the interaction of
acyclovir with zidovudine on progression to AIDS and survival:
analysis of data in the Multicenter AIDS Cohort Study. Ann Intern
Med 1994 Jul 15; 121:100-8.

INVASIVE BACTERIAL INFECTIONS IN HIV-POSITIVE
CHILDREN.
   Two prospective studies reveal a high incidence of
invasive bacterial infection in HIV-infected infants.
   The first study followed infants born to 104 HIV-infected
mothers in New Haven. There were 23 invasive infections (21
bacteremia and 2 meningitis); 10 of the 21 HIV-infected
infants and 11 of the 83 HIV-negative infants were affected.
Streptococcus pneumoniae was the most commonly isolated
organism. The rate of COMMUNITY-acquired infection was
nearly three times higher in the HIV-infected infants (5
infections per 492 months of observation) than in the non-
HIV-infected infants (10 per 2711 months).
   A Baltimore study compared 41 HIV-infected children of
HIV-infected mothers with 128 HIV-negative children of HIV-
infected mothers and 71 HIV-negative children whose mothers
had HIV risk factors. During the first three years of life,
the HIV-infected group had 11.3 invasive pneumococcal
infections per 100 child-years as compared with 1.1 and 0.5
per 100, respectively, in the two comparison groups,
yielding a relative risk of 12.6 for HIV-positive children.
   Comment: Both studies acknowledge potential detection
bias (i.e., less aggressive workup of fever in children
thought to be HIV-negative), but this was probably minimized
by the fact that HIV-negative children could not be
identified as such for many months. The high frequency of
pneumococcal disease suggests the need for preventive
efforts in HIV-infected children; until there are clinical
guidelines or further data, clinicians should consider
prophylactic antibiotics, pneumococcal vaccine, and/or
aggressive management of febrile illness. --RH Pantell.
   Citation: Andiman WA; et al. Invasive bacterial infections in
children born to women infected with human immunodeficiency virus
type 1. J Pediatr 1994 Jun; 124:846-52.
   Citation: Farley JJ; et al. Invasive pneumococcal disease
among infected and uninfected children of mothers with human
immunodeficiency virus infection. J Pediatr 1994 Jun; 124:853-8.

PROGRESS TOWARD POLIO ERADICATION.
   In 1988, the World Health Organization targeted
poliomyelitis for global eradication by the year 2000
through increased routine immunization, campaigns to
immunize certain populations, and rigorous worldwide
surveillance. As of 1993, surveillance data show substantial
progress toward this goal.
   In the Americas, immunization coverage increased from 82
percent in 1988 to 86 percent in 1993, and the number of
reported cases fell from 340 to 0. The last confirmed case
of polio in the Americas occurred in Peru in 1991.
   Worldwide, the number of reported cases declined from
32,286 to 9714. Nearly 70 percent of countries reported no
cases in 1993. Paralytic polio is still highly endemic on
the Indian subcontinent, and cases occur in much of sub-
Saharan Africa and Asia, including many countries of the
former Soviet Union. Imported cases continue to cause
outbreaks in otherwise protected countries, including 71
cases among members of an unvaccinated religious group in
the Netherlands in 1992-93.
   Comment: It looks possible to drive polio from the
planet, but only with very strict vaccination and
surveillance efforts. One interesting strategy is the use of
"National Immunization Days" in countries where polio
remains endemic. --DM Berwick.
   Citation: Progress toward global eradication of poliomyelitis,
1988-1993. MMWR 1994 Jul 15; 43:499-503.

FLUVASTATIN FOR HYPERCHOLESTEROLEMIA.
   Of the available HMG-coenzyme-A reductase inhibitors,
fluvastatin costs the least, has no circulating active
metabolites, and is almost completely absorbed and protein-
bound. This double-blind trial evaluated its short-term
safety and efficacy in lowering cholesterol, both alone and
in combination with niacin.
   The authors randomized 74 patients with LDL cholesterol
levels above 159 mg/dl despite dietary therapy to either
fluvastatin (20 mg daily) or placebo for six weeks. Niacin,
titrated up to 3 grams daily, was then added to both
regimens for nine weeks. Fluvastatin lowered LDL cholesterol
by 21 percent, significantly more than placebo (1 percent).
Fluvastatin plus niacin lowered LDL cholesterol by 40
percent, versus 25 percent for niacin alone. No serious side
effects were seen with either fluvastatin alone or the
combination.
   Comment: Although fluvastatin is effective in lowering
LDL cholesterol, it is useful to remember that other agents
-- such as lovastatin, pravastatin, and simvastatin --
typically lower LDL cholesterol by 30 to 40 percent and that
their effects are also potentiated by agents such as niacin.
Unfortunately, the safety of combination therapy with
fluvastatin or other HMG-CoA reductase inhibitors can only
be evaluated by large studies with long follow-up periods.
--CD Mulrow.
   Citation: Jacobson TA; et al. Fluvastatin with and without
niacin for hypercholesterolemia. Am J Cardiol 1994 Jul 15;
74:149-54.