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  Contents copyright 1994, Mass. Medical Society.

Journal Watch Summaries for August 12, 1994

IS LONG-TERM OMEPRAZOLE SAFE?.
  Ann Intern Med 1994 Aug 1; 121:161-7.

DO BENIGN {*filter*}LESIONS LEAD TO CANCER?.
  N Engl J Med 1994 Aug 4; 331:300-2.

REVERSING LOSS OF HYPOGLYCEMIA AWARENESS.
  Lancet 1994 Jul 30; 344:283-7.

NEBULIZED BUDESONIDE FOR OUTPATIENTS WITH CROUP.
  N Engl J Med 1994 Aug 4; 331:285-9.

PCR FOR FAST DIAGNOSIS OF INFANT ENTEROVIRAL
MENINGITIS.
  Pediatrics 1994 Aug; 94:157-62.

BCG VACCINE IS EFFECTIVE, BUT LOCAL REACTIONS ARE
COMMON.
  J Infect Dis 1994 Aug; 170:476-9.

ATOVAQUONE: AN ALTERNATIVE TREATMENT FOR PCP.
  Ann Intern Med 1994 Aug 1; 121:174-80.

IS LONG-TERM OMEPRAZOLE SAFE?.
   Omeprazole is approved only for short-term use in the U.S.
because of concern that potent, long-term acid
suppression may induce gastric neoplasia. Yet many
clinicians prescribe long-term omeprazole for severe reflux
esophagitis because of its proven superiority to H2-
blockers. This study evaluated long-term omeprazole in 91
patients with reflux esophagitis refractory to H2-blockers.
   Patients received omeprazole for an average of 4 years.
The initial dose was 40 mg daily until endoscopic healing (4
to 16 weeks), followed by a maintenance dose of 20 mg daily.
Initially, all patients responded to omeprazole, but nearly
half eventually needed dose increases to maintain remission
after endoscopically documented relapse.
   As expected, chronic omeprazole therapy increased serum
gastrin levels. Serial gastric biopsies showed that the 10
patients with gastrin levels above 500 ng/l were more likely
than other patients to progress to atrophic gastritis and
micronodular argyrophil cell hyperplasia (a potential
precursor of gastric carcinoid).
   Comment: This study confirms that omeprazole therapy is
effective for several years. Whether the gastric histologic
changes found in some chronically treated patients will
eventually progress to neoplasia remains to be seen.
--AS Brett.
   Citation: Klinkenberg-Knol EC; et al. Long-term treatment with omeprazole
for refractory reflux esophagitis: efficacy and safety. Ann Intern Med 1994
Aug 1; 121:161-7.

DO BENIGN {*filter*}LESIONS LEAD TO CANCER?.
   One school of thought about benign {*filter*}lesions holds
that the inflammatory changes predispose patients to {*filter*}
cancer. To test this theory, researchers in Denmark used
national hospitalization and cancer registry data for 1977
to 1989 to examine the association between benign {*filter*}
lesions (hemorrhoids, fissures, fistulas, and peri{*filter*}
abscesses) and {*filter*}cancer.
   The relative risk for {*filter*}cancer was significantly
elevated during the first year after hospitalization for
benign lesions (12.0), but decreased with time (4.6 during
years 1 to 4, and a nonsignificant 1.8 during years 5 to
13). Similarly, the relative risk for colorectal cancer was
increased during the first year (2.6), but this risk
disappeared during later years.
   Comment: The researchers believe that the waning relative
risk over time is evidence against the theory that benign
{*filter*}lesions cause cancer. Instead, they believe that benign
lesions bring adjacent cancers to attention, or that some
benign lesions are complications of yet-to-be-diagnosed
cancers. While this speculation is probably correct, this
retrospective analysis, limited to hospitalized patients,
does not absolutely exclude an occasional cause and effect
relationship. --AS Brett.
   Citation: Frisch M; et al. Benign {*filter*}lesions and the risk of {*filter*}cancer.
N Engl J Med 1994 Aug 4; 331:300-2.

REVERSING LOSS OF HYPOGLYCEMIA AWARENESS.
   Why some diabetics lose awareness of hypoglycemia is
not clear. One theory holds that repeated exposure to
hypoglycemia eventually blunts the sensitivity of the
glycemic regulatory system. This small study supports this
notion, and shows that careful avoidance of hypoglycemia can
restore hypoglycemia awareness.
   Twelve long-time, insulin-dependent diabetics who had
lost hypoglycemia awareness (six with scrupulous glycemic
control and six with wide swings in {*filter*} sugar) were placed
in a rigorous treatment program designed to achieve at least
a three-week period without low {*filter*}-sugar recordings (this
required an average of 4 months' supervision). Physiologic
responses to induced hypoglycemia were measured before and
after the intervention.
   After intervention, there was a significant increase in
the glucose threshold at which hypoglycemia caused warning
symptoms and release of counter-regulatory hormones (except
for glucagon) and a larger maximal hormone response. The
threshold for cognitive dysfunction did not change, but
subjects did become aware of hypoglycemia before cognitive
impairment set in. Long-term glycemic control did not
deteriorate substantially.
   Comment: These findings are of particular interest in
light of recent evidence that tight diabetic control, with
its associated increase in hypoglycemic episodes, reduces
complications of diabetes (see JW vol. 12, pp. 27 and 57).
Physicians treating diabetic patients have to tread an
increasingly fine line between extremes of glycemic control.
--B Jarman.
   Citation: Cranston I; et al. Restoration of hypoglycaemia awareness in
patients with long-duration insulin-dependent diabetes. Lancet 1994 Jul 30;
344:283-7.

NEBULIZED BUDESONIDE FOR OUTPATIENTS WITH CROUP.
   Clinical trials have shown that corticosteroids are
beneficial for children hospitalized with croup, but it is
unclear whether steroids should be given to outpatients with
milder disease. This randomized, double-blind study,
conducted in an Ontario emergency department, compared a
single dose of nebulized budesonide (2 mg) with placebo
(nebulized saline) in 54 children with mild to moderate
croup who did not respond to breathing humidified oxygen for
15 minutes.
   At four hours, the budesonide group had significantly
better croup scores than the placebo group on a standardized
rating scale. Global assessments by parents, treating
physicians, and a research assistant all favored budesonide.
Seven placebo-treated children, but only one budesonide-
treated child, required hospital admission during the
following week. No side effects were noted.
   Comment: Nebulized budesonide appears to be a safe and
effective treatment for children with mild to moderate
croup. Further studies should examine whether inhaledsteroids
are superior to {*filter*}or injected steroids. --AS Brett.
   Citation: Klassen TP; et al. Nebulized budesonide for children with mild-
to-moderate croup. N Engl J Med 1994 Aug 4; 331:285-9.
   Citation: Landau LI; Geelhoed GC. Aerosolized steroids for croup.
N Engl J Med 1994 Aug 4; 331:322-3.

PCR FOR FAST DIAGNOSIS OF INFANT ENTEROVIRAL
MENINGITIS.
   Enteroviruses commonly cause meningitis, especially in
young children. The clinical features of enteroviral disease
often overlap with those of bacterial meningitis. The
uncertain diagnosis requires hospitalization and treatment
for potential bacterial (and perhaps herpetic) meningitis
until culture results are available. This study shows that
polymerase-chain-reaction (PCR) testing offers a more rapid,
more reliable diagnosis.
   Researchers performed PCR retrospectively on
cerebrospinal-fluid specimens from 27 infants less than 3
months old who had excessive CSF white {*filter*} cells, and
compared the results with viral cultures. Six infants had
enteroviruses cultured from CSF, and three from other
sources; PCR was positive in all nine infants. Thir{*filter*}
infants had suspected enteroviral meningitis but either had
negative viral cultures or did not have cultures performed;
PCR was positive in 6, including 4 with negative cultures of
CSF. PCR was negative in all 5 infants with documented
bacterial meningitis and in 10 additional infants with
neither CSF pleocytosis nor positive enteroviral cultures.
   Comment: It is not yet time to abandon viral cultures:
not all labs can perform PCR, not all viral meningitis is
caused by enteroviruses, and the above findings have yet to
be confirmed. Still, assuming availability of results within
24 to 48 hours, PCR could reduce hospital days and
unnecessary antibiotic use, since clinicians would no longer
need to wait 3 to 4 days for the results of viral and
bacterial cultures. --RA Dershewitz.
   Citation: Schlesinger Y; et al. Enteroviral meningitis in infancy:
potential role for polymerase chain reaction in patient management.
Pediatrics 1994 Aug; 94:157-62.

BCG VACCINE IS EFFECTIVE, BUT LOCAL REACTIONS ARE
COMMON.
   The increased incidence of tuberculosis and the
emergence of multi-drug-resistant M. tuberculosis strains
have prompted reexamination of the Bacille Calmette-Guerin
(BCG) vaccine in high-risk populations. This study found
that the vaccine effectively induces an immune response, but
causes local reactions in most {*filter*}s.
   Researchers vaccinated 20 healthy, PPD-negative health
care workers with the Glaxo strain of BCG. Two months later,
all vaccine recipients had induration from an intermediate-
strength PPD skin test (mean diameter, 17 mm; range, 7 to 33
mm). One year later, all 18 subjects who returned for skin testing had
induration (range, 4 to 33 mm), and four had increased induration.
   During the two weeks after vaccination, 13 recipients had
pain, 4 reported chills and sweats, 6 had ulceration at the
injection site, and 2 had tender axillary adenopathy. As of
eight weeks, 14 recipients had local ulceration with
drainage; all cases resolved within six weeks. Viable BCG
organisms were recovered from only one patient.
   Comment: Three important problematic issues emerge from
this study: First, the increasing induration on successive
PPD tests can be caused by either new TB infection or BCG
vaccination. Second, there is a question of safety to
immunocompromised contacts of vaccinees, since the BCG
strain may spread through purulent drainage at the
vaccination site. Finally, the local complications of the
vaccine are not trivial. --RA Dershewitz.
   Citation: Brewer MA; et al. Bacille Calmette-Guerin immunization in normal
healthy {*filter*}s. J Infect Dis 1994 Aug; 170:476-9.

ATOVAQUONE: AN ALTERNATIVE TREATMENT FOR PCP.
   Although both trimethoprim-sulfamethoxazole (TMP-SMX)
and pentamidine are effective treatments for Pneumocystis
carinii pneumonia (PCP), many patients cannot tolerate these
agents. This nonblinded trial randomized 109 AIDS patients
with mild to moderate PCP to receive either {*filter*}atovaquone
(750 mg three times daily) or intravenous pentamidine for
three weeks. Most patients had known intolerance to TMP-SMX.
   The rates of treatment success (improvement sustained for
four weeks after completion of therapy) were 57 percent with
atovaquone and 40 percent with pentamidine, a difference
just shy of statistical significance. Treatment-limiting
adverse reactions were significantly less frequent with
atovaquone than with pentamidine (4 vs. 36 percent). The
most common reasons for discontinuing pentamidine were
hypoglycemia, nausea, vomiting, and rash. After excluding
patients who were intolerant of their assigned drug, success
rates were similar in the two groups (59 vs. 62 percent).
   Comment: When patients with mild to moderate PCP cannot
tolerate TMP-SMX but are able to take {*filter*}medication,
atovaquone appears to be a good alternative to pentamidine.
--AS Brett.
   Citation: Dohn MN; et al. {*filter*}atovaquone compared with intravenous
pentamidine for Pneumocystis carinii pneumonia in patients with AIDS. Ann
Intern Med 1994 Aug 1; 121:174-80.