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HICNet Medical News Digest      Wed, 15 Jun 1994        Volume 07 : Issue 26

Today's Topics:

  [MMWR 10 June 94] Risky Driving Behaviors Among Teenagers
  [MMWR] Birth Outcomes Following Zidovudine Use in Pregnant Women
  [MMWR] Multidrug-Resistant Tuberculosis in a Hospital
  [MMWR] Atlanta Conference on Human Health and the Environment
  Boning Up: New Ways to Prevent Fractures in Older Americans
  Vaccine Slows Gum Disease
  An Unexpected Window on High Blood Pressure
  Institute of Tropical Medicine Epidemiological Bulletin

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----------------------------------------------------------------------

Date: Wed, 15 Jun 94 06:42:02 MST
From: mednews (HICNet Medical News)
To: hicnews
Subject: [MMWR 10 June 94] Risky Driving Behaviors Among Teenagers
Message-ID: <[e-mail]>

           Risky Driving Behaviors Among Teenagers --
                 Gwinnett County, Georgia, 1993

     In the United States in 1991, approximately 6000 persons aged
16-20 years died from motor-vehicle crashes (MVCs)--twice as many
as from any other cause of death among persons in this age group
(1). During 1991, approximately 3000 crashes in Gwinnett County,
Georgia (1990 population: 352,910) (26% of all crashes in Gwinnett
County), involved at least one teenage driver (Gwinnett County
Department of Transportation, unpublished data, 1992). Risky
driving behaviors are among the risk factors for teenage MVC death
and injury (2). To better characterize these risk factors, the
Georgia Department of Human Resources, the Gwinnett County Board of
Health, the community-based Gwinnett County Teen Traffic Tragedies
Task Force, and CDC conducted a case-control study of MVCs among
teenage drivers in Gwinnett County during 1993. This report
summarizes the results of that study.
     To be eligible for the study, a person must have been aged 16-
19 years, a licensed driver, and enrolled in a Gwinnett County
public high school. Case-students (n=64) had been involved as
drivers in injury-producing MVCs during January-March 1993
according to Police Accident Reports filed with the Gwinnett County
Department of Transportation. Control-students (n=227) were
randomly selected from enrollment files of Gwinnett County public
high schools; these students had never been involved in a
police-reported crash, were aged 16-19 years, and were licensed
drivers. Participants completed a written questionnaire in which
they specified how often they had engaged in 11 potentially risky
driving behaviors during the 3 months preceding the survey (Table
1). Questions were adapted from a survey on risky driving behavior
(3). Possible responses were "never," "one to two times," "three to
five times," and "six or more times." The chi-square test was used
to assist in assessing associations between behaviors and risk for
MVCs. Three behaviors that appeared to be associated with MVCs and
two additional behaviors thought to be potentially life-threatening
were analyzed further by stratifying by sex.
     For seven of the 11 risky behaviors, at least 50% of both
cases and controls reported engaging in the behaviors at least once
during the 3 months preceding the survey. For example, at least
once during the 3 months preceding the survey, 63% of all
respondents reported tailgating, 80% reported driving 20 miles per
hour (mph) over the speed limit, and 91% reported entering an
intersection when the light was about to turn red. Twenty-six
percent of all students surveyed reported passing in a no-passing
zone, and 21% reported passing two to three cars at once on a
two-lane road.
     When cases and controls were compared, three behaviors
appeared to be associated with risk for MVCs: driving 20 mph over
the speed limit (p=0.06), passing a car in a no-passing zone
(p=0.06), and taking risks while driving in traffic because it
makes driving more fun (p=0.07). For these behaviors, differences
were greatest for those who reported engaging in the behaviors six
or more times during the 3 months preceding the survey (Table 1).
At this level, 28 (44%) cases and 65 (29%) controls reported
driving 20 mph over the speed limit; five (8%) cases and nine (4%)
controls reported passing a car in a no-passing zone; and 12 (19%)
cases and 18 (8%) controls reported taking some risks while driving
in traffic because it makes driving more fun.
     Compared with male controls and all females, male cases were
more likely to drive 20 mph over the speed limit (p=0.02), pass a
car in a no-passing zone (p=0.05), take driving risks for fun
(p=0.04), and pass two to three cars at once on a two-lane road
(p=0.09) (Table 2).

Reported by: Gwinnett County Teen Traffic Tragedies Task Force; JC
Crutcher, MD, Gwinnett County Board of Health; G Black, P Campbell,
Gwinnett County Dept of Transportation, Lawrenceville; JD Smith, K
Toomey, MD, State Epidemiologist, Georgia Dept of Human Resources.
Div of Unintentional Injury Prevention, Div of Acute Care and
Rehabilitation Research and Disability Prevention, Office of
Statistics, Programming, and Graphics, National Center for Injury
Prevention and Control, CDC.

Editorial Note: Young drivers account disproportionately for MVCs
worldwide (4), reflecting, in part, the combination of immaturity
and lack of driving experience (5). Adolescent drivers are more
likely than adult drivers to report speeding, running red lights,
making illegal turns, not wearing safety belts, riding with an
intoxicated driver, and driving after using drugs or alcohol (6).
     In the Gwinnett County study, most students--regardless of
whether they were cases or controls--reported engaging in risky
driving behaviors. Parents should recognize that driving is a
complex task that can take several years to master and can assist
in reducing the risk for MVCs among adolescent drivers by 1)
providing young drivers a longer period of supervised driving in
low-risk settings (e.g., with supervision, during daylight, and in
safe environments) in addition to traditional driver's education
courses, 2) serving as role models by practicing good driving
behaviors and always obeying traffic laws, and 3) requiring all
family members to be properly restrained each time they ride in a
motor vehicle.
     The findings in this report are subject to at least five
limitations. First, because respondents were students who were
licensed drivers enrolled in public schools, the study did not
include students in private schools, youth not enrolled in school,
and drivers with learners' permits. Second, because the study
assessed only MVCs that occurred during January-March 1993, the
effects of seasonal trends could not be analyzed. Third, the study
did not include MVCs that resulted only in property damage or were
not reported to the police. Fourth, other potential risk factors
(e.g., alcohol use) were not analyzed in this report, although they
were included in the study. Finally, the analysis of findings in
this case-control study was influenced by the high prevalences of
risky behaviors among members of both the case and control groups.
     Graduated driver licensing is one strategy for promoting safe
driving behaviors and reducing the incidence and severity of MVCs
among young drivers. This method allows new drivers to accumulate
driving experience in low-risk settings and gradually lifts
restrictions until an unrestricted license is earned (7). In
addition, because up to 24 months may be required to obtain an
unrestricted license, drivers are older and more mature when they
become fully licensed. Driving restrictions may include prohibiting
unsupervised nighttime driving, requiring zero or near-zero blood
alcohol concentration, requiring all occupants to be properly
restrained, and limiting the number of passengers and the distances
and types of roads traveled. The threshold for corrective action
(e.g., a lengthened restriction period) may be lower for restricted
drivers than for unrestricted drivers. Graduated licensing systems
have been instituted in Australia, New Zealand, and Ontario,
Canada. Although this system has not been implemented in the United
States, the National Highway Traffic Safety Administration is
providing funds to states to evaluate the impact of various
elements of the graduated licensing system.
     The Gwinnett County Teen Traffic Tragedies Task Force is
planning to use findings from this study to assist in developing
and targeting specific intervention strategies for reducing MVC
injuries and deaths among young drivers.

References
1. National Highway Traffic Safety Administration. Fatal Accident
Reporting System, 1991: a review of information on fatal traffic
crashes in the United States. Washington, DC: US Department of
Transportation, National Highway Traffic Safety Administration,
1992.
2. Insurance Institute for Highway Safety. Teenage drivers:
questions and answers. Arlington, Virginia: Insurance Institute for
Highway Safety, 1993.
3. Donovan JE, Jessor R. Young adult driving questionnaire.
Boulder, Colorado: University of Colorado Institute of Behavioral
Science, 1992.
4. Evans L. Traffic safety and the driver. New York: Van Nostrand
Reinhold, 1991.
5. Mayhew DR, Simpson HM. New to the road: young drivers and novice
drivers: similar problems and solutions? Ottawa: Traffic Injury
Research Foundation of Canada, 1991.
6. Hingson R, Howland J. Promoting safety in adolescents. In:
Millstein SG, Petersen AC, Nightingale EO, eds. Promoting the
health of adolescents: new directions for the twenty-first century.
New York: Oxford University Press, 1993.
7. Insurance Institute for Highway Safety. Slower graduation to
full licensing means fewer teenage deaths. In: Status report.
Arlington, Virginia: Insurance Institute for Highway Safety
1994;29(4):1-3.



------------------------------

Date: Wed, 15 Jun 94 06:43:06 MST
From: mednews (HICNet Medical News)
To: hicnews
Subject: [MMWR] Birth Outcomes Following Zidovudine Use in Pregnant Women
Message-ID: <[e-mail]>

           Birth Outcomes Following Zidovudine Therapy
                        in Pregnant Women

     Approximately 100,000 childbearing-aged women in the United
States are infected with human immunodeficiency virus (HIV), and an
estimated 7000 infants are born to HIV-positive mothers each year
(1). In the United States, the rate of perinatal transmission of
HIV among mothers who do not receive antiretroviral therapy is 15%-
30% (2). Results from a recent multicenter randomized double-blind
clinical trial suggest that treatment of HIV-positive mothers and
their infants with zidovudine (ZDV) may substantially reduce the
risk for perinatal HIV transmission (3). However, any potential
risk for adverse outcomes associated with use of antiretrovirals
during pregnancy should be considered. This report summarizes data
from the Antiretroviral Pregnancy Registry regarding use of ZDV and
the occurrence of structural birth defects reported for pregnancies
registered during January 1989-December 1993.
     In January 1989, the Zidovudine in Pregnancy Registry was
established by the Wellcome Foundation, in conjunction with CDC,
and has been managed by the Burroughs Wellcome Co. (Research
Triangle Park, North Carolina),* the manufacturer of ZDV. In
January 1993, the Zidovudine in Pregnancy Registry was expanded to
include zalcitabine and became the Antiretroviral Pregnancy
Registry. Although ZDV is not yet approved for use during
pregnancy, physicians and other health professionals have provided
to the registry reports of women who received antiretroviral
therapy during pregnancy. The purpose of the worldwide registry is
to measure the incidence of infants with structural defects among
prospectively registered cases (i.e., those registered predelivery)
and to monitor potential patterns of defects by collecting data on
outcomes of pregnancies registered retrospectively (i.e., cases
reported post-delivery). A prenatal exposure to ZDV is defined as
inadvertent or intentional use of oral or intravenous ZDV at any
time during pregnancy. The registry follows CDC guidelines for
definitions of major birth defects (4).
     Physicians provide information regarding pregnancy dates,
lowest CD4+ T-cell count, CDC classification of HIV disease,
dosage, length of therapy, and trimester of exposure to
antiretroviral drugs. At the expected delivery date, a follow-up
form is sent to the physician to ascertain the pregnancy outcome
and occurrence of concurrent illnesses.
     From 1989 through 1993, 198 prenatal exposures to ZDV were
reported prospectively. As of December 31, 1993, 30 women were
still awaiting delivery. Of the other 168 women, 47 (28%) were lost
to follow-up--39 (83%) because the initial reporting physician did
not respond to inquiries after the date of expected delivery.
Reports are considered lost to follow-up only after efforts to
obtain information have been made by sending at least three monthly
letters and making one telephone call after the expected delivery
date or if the reporting physician can no longer locate the
patient.
     Of the 121 prospectively registered women, four delivered
infants with structural birth defects. ZDV therapy in 54
pregnancies occurred during the first trimester: among these 54
women, one infant was born with a birth defect (agenesis of the
right kidney), and 45 infants were born without defects; eight
pregnancies were terminated by induced abortions. Among 47 women
who received ZDV therapy during the second trimester, three infants
were born with birth defects (pectus excavatum, atrial septal
defect, and fetal alcohol syndrome), and 44 infants were born
without defects. No birth defects occurred among infants born to
the 20 women who received ZDV therapy during the third trimester.
     Indications for ZDV treatment of the 121 women included
asymptomatic HIV infection with low CD4+ count (97), treatment for
acquired immunodeficiency syndrome (AIDS) (nine), symptomatic HIV
infection (six), and prophylaxis following needlestick injury
(six); indications were unknown for three women.
     Of the pregnancies registered retrospectively, four infants
were born with defects following third trimester ZDV therapy (extra
digits; asymptomatic ventricular septal defect; left hydronephrosis
and ureteral pelvic junction obstruction; and two-vessel cord,
hypoplastic left heart and mitral atresia).

Reported by: A White, PhD, E Andrews, PhD, R Eldridge, M Dickerson,
H Tilson, MD, International Div of Surveillance, Epidemiology, and
Economics Research; M Elkins, Infectious Diseases, Burroughs
Wellcome Co, Research Triangle Park, North Carolina. W Dai, MD, Div
of Drug Safety, Hoffmann-LaRoche, Inc, Nutley, New Jersey. B Hurn,
MD, Clinical and Safety Surveillance Svc, Wellcome Research
Laboratories, Beckenham, England. ER Alexander, Seattle-King County
Health Dept, Seattle. H Fox, Dept of Obstetrics and Gynecology,
Columbia Presbyterian Medical Center, New York. P Garcia, MD,
Prentice Hospital, Chicago. A Rogers, Pediatric, Adolescent, and
Maternal AIDS Br, Center for Research for Mothers and Children,
National Institute of Child Health and Human Development, National
Institutes of Health. Div of Sexually Transmitted Diseases and HIV
Prevention, National Center for Prevention Svcs; Div of HIV/AIDS;
National Center for Infectious Diseases; Div of Birth Defects and
Developmental Disabilities, National Center for Environmental
Health, CDC.

Editorial Note: Based on findings in the registry, the observed
proportion of birth defects among infants of women who received ZDV
therapy during the first trimester of pregnancy (when the fetus is
most sensitive to teratogens [5]) was 2% (1 of 46). This does not
differ from the expected proportion in the general population (3%)
(4). Neither the prospective nor retrospective reports indicated a
consistent pattern of defects. In addition, cases of birth defects
from the AIDS Clinical Trial Group 076 clinical trial (3) do not
suggest an increase or unusual pattern of birth defects. Public
Health Service agencies are evaluating possible recommendations for
use of ZDV to reduce the risk for perinatal transmission of HIV.
     The findings in this report are preliminary, and the sample
size was limited. Other potential limitations of this and other
registries include differential reporting of pregnancy outcomes,
losses to follow-up, and underreporting. In general, cases lost to
follow-up are more common for observational registries than for
cases obtained from registries using active ascertainment methods.
Retrospective reports may include cases with more unusual or severe
features and may be less representative of the population.
     Because the number of HIV-positive women who use ZDV during
pregnancy may increase, the registry must be sustained to monitor
for possible teratogenicity among infants of women receiving ZDV or
other antiretroviral therapy during pregnancy. Physicians who
provide care for women treated with ZDV or zalcitabine can register
patients by calling the registry, [phone], extension 8465,
in the United States or by calling [phone] for registrations
from countries outside the United States. Copies of the semiannual
registry report are available to health professionals by calling
these numbers or by writing to the Antiretroviral Pregnancy
Registry, P.O. Box 12700, Research Triangle Park, NC 27709.

References
1. CDC. National HIV serosurveillance summary: results through
1992. Vol 3. Atlanta: US Department of Health and Human Services,
Public Health Service, CDC, 1994.
2. CDC. 1993 Sexually transmitted diseases treatment guidelines.
MMWR 1993;42(no. RR-14).
3. CDC. Zidovudine for the prevention of HIV transmission from
mother to infant. MMWR 1994;43:285-7.
4. CDC. Congenital malformations surveillance report, January 1982-
December 1985. Atlanta: US Department of Health and Human Services,
Public Health Service, CDC, 1988.
5. Tuchmann-Duplessis H. Drug effects on the fetus. New York: Adis
Press, 1977.

*Use of trade names and commercial sources is for identification
only and does not imply endorsement by the Public Health Service or
the U.S. Department of Health and Human Services.



------------------------------

Date: Wed, 15 Jun 94 06:44:03 MST
From: mednews (HICNet Medical News)
To: hicnews
Subject: [MMWR] Multidrug-Resistant Tuberculosis in a Hospital
Message-ID: <[e-mail]>

                Multidrug-Resistant Tuberculosis
       in a Hospital -- Jersey City, New Jersey, 1990-1992

     Since 1986 (the first full year following implementation of
the revised tuberculosis [TB] surveillance case definition), the
reported rate of TB per 100,000 persons in New Jersey increased
from 9.5 cases to 12.6 cases in 1992 (1). Of the 984 cases reported
to CDC from New Jersey in 1992, 108 (11.0%) were reported from
Jersey City (1990 population: 230,300)--the city ranked second in
number of TB cases reported (1) and fourth in rate of TB (46.9 per
100,000) in the state. In addition, in 1992, the rate of
multidrug-resistant TB (MDR-TB) (i.e., Mycobacterium tuberculosis
isolates resistant to at least isoniazid [INH] and rifampin [RIF])
among TB patients in New Jersey was 5%; the rate in Jersey City was
13% (1,2). To characterize the epidemiologic features of persons
with drug-resistant TB, the New Jersey Department of Health and the
Infectious Diseases Division of the Jersey City Medical Center
conducted a study among patients treated at that hospital during
1990-1992. This report presents the findings of the study and
compares the hospital's rates of drug-resistant TB with previously
reported rates, rates for other cities in New Jersey, and rates for
the state.
     The hospital serves a predominantly inner-city population and
treats more than 40% of TB patients in Jersey City. Information
about hospital inpatients with TB was abstracted from
mycobacteriology log books and TB reporting forms. Mycobacterial
species identification and drug-susceptibility testing were
performed at the New Jersey Public Health Laboratory (NJPHL) or a
commercial laboratory. The DNA probe method was used for species
identification (3). Drug susceptibility was determined by the
radiometric method for NJPHL and the conventional plate method for
the commercial laboratory (4).
     Data were analyzed for all 146 patients with culture-positive
M. tuberculosis during 1990-1992. Of the 142 patients for whom TB
reporting forms were available, 131 (92%) had had
drug-susceptibility tests performed for anti-TB drugs. Patients
ranged in age from 11 to 79 years (mean: 40 years); 95 (73%)
patients were male. A total of 36 (28%) patients had extrapulmonary
TB. Although no serologic survey for human immunodeficiency virus
(HIV) infection was performed, matching of state TB records with
state HIV/acquired immunodeficiency syndrome records indicated that
at least 58 (44%) TB patients had concurrent HIV infection.
     Of the 131 patients for whom drug-susceptibility testing had
been performed, 32 (24%) had M. tuberculosis isolates resistant to
at least one drug, and 21 (16%) had MDR-TB (Table 1). Of the six
patients with a prior history of TB, four (67%) had MDR-TB,
compared with 17 (14%) of the 125 patients with no prior history of
TB (relative risk [RR]=4.9). Of the 97 patients known to have been
born in the United States, 23 (24%) had TB resistant to at least
one anti-TB drug, and 12 (12%) had MDR-TB; in comparison, of the 22
known foreign-born patients, four (18%) had MDR-TB (RR=0.7). Of the
18 foreign-born patients for whom information was available, seven
had resided in the United States for 5 or fewer years before
diagnosis of TB. Of those seven, two (29%) had MDR-TB, compared
with two (18%) of the 11 persons who had resided in the United
States more than 5 years (RR=1.6). Among these 131 patients, drug
resistance was not associated with sex, age, race, or known HIV
infection; because these cases were not associated with clustering
in time or location in the hospital, nosocomial transmission of M.
tuberculosis was unlikely.

Reported by: A Lin-Greenberg, MD, Jersey City Medical Center,
Jersey City; A Cortes, Tuberculosis Control Program, New Jersey
Dept of Health. Div of Tuberculosis Elimination, National Center
for Prevention Svcs; Div of Field Epidemiology, Epidemiology
Program Office, CDC.

Editorial Note: The findings in this report indicate that the rate
of MDR-TB in New Jersey varied widely: the rate among patients
treated at the hospital described in this report during 1990-1992
was similar to that for Jersey City in 1992 but substantially
higher than that reported for the state and for other New Jersey
cities (2). For example, in Newark in 1992, the rate of MDR-TB was
nearly one third (5%) of that reported for the Jersey City
hospital, and although the number of isolates tested was small, no
cases of MDR-TB were reported from Trenton or Camden--urban areas
with demographic and socioeconomic compositions similar to Jersey
City's (2). In addition, the rate of primary INH resistance among
patients at the hospital in Jersey City was higher during 1990-1992
(21%) than during 1984-1986 (15%), while the rates of presumptive
primary MDR-TB during 1990-1992 and 1984-1986 were similar (14% and
13%, respectively) (5).
     The higher rate of MDR-TB among patients in the hospital in
Jersey City than in Newark and for the state of New Jersey may
reflect a greater prevalence of nonadherence to treatment and/or
exposure to persons with drug-resistant TB--known risk factors for
drug resistance (6). Jersey City is located near New York City, in
which 19% of patients with TB in 1991 had MDR-TB (7) and outbreaks
of MDR-TB have occurred recently (8). In addition, the five
counties in New Jersey that reported more than one case of MDR-TB
in 1992 are located closest to New York City (2). The findings in
this report also are consistent with previous reports indicating an
association between MDR-TB and prior history of TB (6).
     The pattern of anti-TB drug resistance in Jersey City and
other communities in New Jersey illustrates the substantial
geographic variations in this problem, even within a small state.
Knowledge of local resistance patterns is critical for determining
optimal treatment regimens before drug-susceptibility test results
are available. As a result of this study, use of directly observed
therapy was instituted in hospitals throughout Jersey City. In
areas with rates of INH resistance of 4% or more, anti-TB treatment
should be initiated with four drugs (INH, RIF, pyrazinamide, plus
either ethambutol or streptomycin), and directly observed therapy
should be used (9). Institutions experiencing outbreaks or high
rates of MDR-TB may need to begin five- or six-drug regimens as
initial therapy. These regimens should include the four-drug
regimen and at least three drugs to which the suspected MDR strain
may be susceptible (9).

References
1. Bureau of Tuberculosis Control, New Jersey Department of Health.
Annual report, 1992. Trenton, New Jersey: New Jersey Department of
Health, Bureau of Tuberculosis Control, 1993.
2. Bureau of Tuberculosis Control, New Jersey Department of Health.
Multiple drug-resistant tuberculosis in New Jersey. Trenton, New
Jersey: New Jersey Department of Health, Bureau of Tuberculosis
Control, 1992.
3. Body BA, Warren NG, Spicer A, Henderson D, Chery M. Use of
Gen-Probe and Bactec for rapid isolation and identification of
mycobacteria: correlation of probe results with growth index. Am J
Clin Pathol 1990;93:415-20.
4. Heiferts L. Qualitative and quantitative drug susceptibility
tests in mycobacteriology. Am Rev Respir Dis 1988;137:1217-21.
5. Lin-Greenberg A, Deltieure M. Primary resistance to
anti-tuberculosis drugs in a New Jersey hospital. New Jersey
Medicine 1987;84:427-8.
6. Barnes PF. The influence of epidemiologic factors on drug
resistance rates in tuberculosis. Am Rev Respir Dis 1987;136:325-8.
7. Frieden TR, Sterling T, Pablos-Mendez A, Kilburn JO, Cauthen GM,
Dooley SW. The emergence of drug-resistant tuberculosis in New York
City. N Engl J Med 1993;328:521-6.
8. CDC. Nosocomial transmission of multidrug-resistant tuberculosis
among HIV-infected persons--Florida and New York, 1988-1991. MMWR
1991;40:585-91.
9. CDC. Initial therapy for tuberculosis in the era of multidrug
resistance: recommendations of the Advisory Council for the
Elimination of Tuberculosis. MMWR 1993;42(no. RR-7).



------------------------------

Date: Wed, 15 Jun 94 06:44:54 MST
From: mednews (HICNet Medical News)
To: hicnews
Subject: [MMWR] Atlanta Conference on Human Health and the Environment
Message-ID: <[e-mail]>

     Atlanta Conference on Human Health and the Environment

     The Agency for Toxic Substances and Disease Registry and CDC
are cosponsors of the Atlanta Conference on Human Health and the
Environment in Atlanta on June 24-26, 1994. The conference will
present information about environmental degradation and the effects
of global changes to the environment on human health; workshops
will focus on clinical and community aspects of specific
environmental hazards. The conference is targeted toward
physicians, scientists, other health-care workers, journalists, and
environmentalists. Participants can earn Continuing Medical
Education credits. Registration information is available from
Physicians for Social Responsibility/Atlanta, P.O. Box 95190,
Executive Park, Atlanta, GA 30347; telephone [phone]; fax
[phone].



------------------------------

Date: Wed, 15 Jun 94 06:46:18 MST
From: mednews (HICNet Medical News)
To: hicnews
Subject: Boning Up: New Ways to Prevent Fractures in Older Americans
Message-ID: <[e-mail]>

Boning Up: New Ways to Prevent Fractures in Older Americans
by Ole Henriksen, PhD
NCRR Reporter, May/June 1994

As we age, our bones age too.  Because they are thinner and more
brittle, they are far too easily broken in a fall. Often they heal
slowly and painfully if they heal at all. The kind of fall that matters
little to someone younger can bring independent living to an abrupt
halt. In some cases, bones fracture spontaneously because they are
unable to carry out their normal weightsupporting role. Through studies
that approach this problem from very different perspectives, two
independent teams of NCRR-supported investigators have arrived at
results that could help prevent bone fractures among older Americans.

The first team of investigators, based at the General Clinical Research
Center (GCRC) at the University of Texas Southwestern Medical Center at
Dallas, has shown that an experimental treatment with sodium fluoride,
the chemical that is added to drinking water, can stimulate mineral
buildup and prevent new fractures in osteoporotic bones of the spinal
column. Osteoporosis-the hollowing out of bones caused by reduced
mineral content-affects more than 25 million Americans, including one of
every three postmenopausal women.

At the beginning of the study, which included 110 postmenopausal
osteoporotic patients, the average mineral content of the women's
lower-back vertebrae was approximately 30 percent below that of a
30-year-old normal woman, and they all had spinal compression fractures.
According to Dr. Charles Y. C. Pak, GCRC principal investigator and
Distinguished Chair in Mineral Metabolism at the Southwestern Medical
Center, painful spontaneous fractures often develop in the lower part of
the spine in osteoporotic women. "The strength of the bone is not
sufficient to sustain the weight-bearing function of the skeleton, so
the spine becomes compressed and fractures develop," he explains.
Fractures of the spine can cause back pain and deformity; damage to
several vertebrae in the upper spine results in "dowager's hump."

Investigators conducting the ongoing trial randomized the 110 patients
into two groups. One group (54 patients) receives slowrelease sodium
fluoride tablets two times daily in repeated 14-month cycles (12 months
treatment, 2 months withdrawal). The other group (56 patients) receives
a placebo preparation on the same schedule. All patients receive calcium
citrate tablets twice daily continuously as an optimally absorbable
calcium supplement. Once a year the researchers determine how many
spontaneous vertebral fractures the patients have developed and measure
the mineral content of vertebrae and other bones. To date, 48 of the
patients taking sodium fluoride have completed more than one cycle
(mean of 2.5 cycles) of treatment. Eleven patients withdrew from the
study prior to completing a full treatment cycle.

Interim analysis of the trial data in the remaining 99 patients shows
that the treatment caused a continued 4-6 percent increase per cycle in
vertebral bone mineral density in the fluoride-treated group, but did
not result in any significant change in the placebo group. The
fluoride-treated group developed substantially fewer spontaneous spinal
fractures (10 new fractures) than did the placebo group (26 new
fractures).

Researchers did not observe any significant side effects among treated
patients, in contrast to earlier studies that have linked high levels of
sodium fluoride intake with many side effects, including severe
diarrhea, gastrointestinal bleeding, microfractures, and an increased
rate of nonspinal fractures. Studies by other researchers have also
previously reported that sodium fluoride administration promotes buildup
of abnormal bone structure, but Dr. Pak and his colleagues use lower
doses of a different type of sodium fluoride. "We use a slow-release
preparation. Sodium fluoride leaks out of numerous tiny holes in the wax
matrix tablets we use," he says. The slow release prevents high
concentrations of fluoride in the stomach and blood.

If the concentration of sodium fluoride delivered to bone were high - as
it was in other studies - and the amount of available calcium were low,
the newly formed bone could be defective, Dr. Pak notes. "Sodium
fluoride should not be given without adequate calcium. It could produce
collagen, the bone matrix, but that would fail to mineralize, resulting
in defective bone formation," he says. In addition, in contrast to the
damaging effects on cortical bone seen by researchers in other studies,
interim results in the current trial indicate "absolutely no change in
cortical bone density and quality says Dr. Pak. "Our findings show that
this approach can greatly reduce new fractures, and they support the
hypothesis we have had since the beginning of this work. That is, given
in proper amounts with adequate calcium, fluoride is a means to form
normal bone."

The Texas researchers plan to follow the patients through four cycles of
treatment.  The investigators have also initiated a similar study on a
group of women who have lower than normal bone density but no
compression fractures. They hope that the earlier treatment may prevent
development of fractures.  In the second investigation, a team of
researchers has evaluated the mechanics of falls and suggested
preventive methods to reduce the risk of hip fracture, the most
devastating fall injury. Hip fracture, which affects more than 250,000
Americans each year, is the second leading cause of nursing home
placement in the United States and exacts an estimated $8.7 billion
annual cost to society.

Dr. Susan L. Greenspan and her colleagues at Beth Israel Hospital in
Boston studied 149 ambulatory men and women who had fallen (126 women
and 23 men aged 65 years or older). By falling, 72 patients broke their
hips. These "case" patients were compared to 77 "control" patients who
fell but did not break their hips.

By examining how people fell, the investigators found that a fall to the
side carried a significant risk of hip fracture. In contrast, there was
no increased risk of hip fracture associated with forward, backward, or
straight-down falls, in which the individual collapses vertically to the
floor.  It has been estimated that only about 5 percent of all falls by
the elderly result in hip fracture. According to Dr. Greenspan, who is
director of the Osteoporosis Prevention and Treatment Center at Beth
Israel Hospital and assistant professor of medicine at Harvard Medical
School, "The relatively low incidence of hip fracture in elderly fallers
probably has a lot to do with factors other than osteoporosis. How
people fall, where they land, and what they fall on-these factors all
play a role. Many elderly persons may be able to break the fall or twist
and turn the body to lessen the impact."

Not surprisingly, the mineral content, or bone mineral density (BMD), of
hip bones was also an independent risk factor in predicting hip fracture
and had a significance similar to that of fall mechanics in determining
the risk of fracture among the study patients. The nondominant role of
BMD in predicting the risk of hip fracture may seem very surprising.
But Dr. Greenspan emphasizes that, since the mean age of her study group
was 83, the majority of women were likely to have had a BMD below the
fracture threshold, the mineral density at which a bone easily breaks.
Other factors, as a result, dominate in this statistical comparison
between very similar people. "Osteoporosis is still very important, but
our study shows that in addition to maintaining bone mass we need to
focus on alternative methods to prevent hip fracture," she says.


People who broke their hips in a fall were generally taller and weighed
slightly less than those who did not break their hips. From the weights
and heights of the study participants, the investigators calculated the
body mass index, BMI (kg/m2). Both women and men with hip fractures had
significantly lower body mass indexes than those who did not break their
hips.

The Boston investigators suggest that current approaches to prevent hip
fracture should be modified. Today most efforts aim to retard bone loss
rather than increase bone mass. In individuals older than 70 years the
bone mineral density is already below a critical risk level for
fracture, but the rate of bone loss has slowed. For these individuals
preventive strategies could also focus on multidisciplinary measures
that are unrelated to bone mass. For example, education about
environmental hazards such as throw rugs, loose electrical cords, poorly
lit stairs, and high-heeled shoes might prevent many accidents.

Dr. Greenspan says that elderly people should also be encouraged to
exercise their muscles to increase their strength in general and the
strength of their thigh muscles in particular. In addition,
their medication should be reviewed in order to eliminate drugs that
affect balance or cause dizziness. Such medications can aggravate
preexisting balance limitations that are common among the elderly and
spring from many causes. "I think that many independent factors - such
as cardiovascular, neuromuscular, and pharmacological problems -  get
compounded and lead to poor balance," says Dr. Greenspan.


Additional Reading
  1. Pak, C. Y. C., Sakhaee, K., Piziak, V., et al., Randomized
        controlled trial of slow-release sodium fluoride in the
        management of postmenopausal osteoporosis. Annals of Internal
        Medicine 120:625432,1994.

  2. Greenspan, S. L., Myers, E. R., Maitland, L. A., et al., Fall
        severity and bone mineral density as risk factors for hip
        fracture in ambulatory elderly. JAMA 271:128-133, 1994.



------------------------------

Date: Wed, 15 Jun 94 06:48:01 MST
From: mednews (HICNet Medical News)
To: hicnews
Subject: Vaccine Slows Gum Disease
Message-ID: <[e-mail]>

Vaccine Slows Gum Disease
by Maureen Curran
NCRR Reporter, May/June 1994


     Researchers at the University of Washington have shown for the first
time that immunization can slow the progression of periodontal disease in
monkeys. The study conducted at NCRR's Regional Primate Research
Center in Seattle, Washington, and supported by the National Institute of
Dental Research, indicates that one day it may be possible to develop a
human vaccine to prevent periodontitis, the major cause of tooth loss
among older Americans. "We know enough already to say that a human
periodontitis vaccine seems feasible, but it may be a decade before we see
full fledged clinical trials of such a vaccine," says Dr. Roy C. Page,
director of the Research Center in Oral Biology at the University of
Washington School of Dentistry, Seattle.

     Periodontitis is a common infectious disease in which the tissues and
bones surrounding and supporting the teeth are destroyed by invading
bacteria. Treatment to restore tooth support can be costly and time-
consuming. One of the primary culprits in periodontal disease is the gram-
negative bacterium , Porphyromonas gingivalis.  The University of
Washington researchers, working with scientists at the University of Texas
in San Antonio and the Bristol Myers Squibb Pharmaceutical Research
Institute in Seattle, have developed a vaccine containing killed
P. gingivalis. The vaccine was tested in long-tailed macaque monkeys
(Macacafascicularis).

     Twenty monkeys were enrolled in the study. They had pre-existing P.
gingivalis infection. Ten randomly chosen monkeys received the vaccine and
10 received placebo inoculations at the start of the study and again at 3,
6, and 16 weeks. At the time of the final injection, the investigators
wrapped silk thread beneath the gum line of eight teeth in each of the
monkeys to induce bacterial buildup and periodontal disease.  Examination
of the animals' gums at intervals after the silk thread was placed showed
that the amount of P. gingivalis and gum inflammation increased
significantly in both groups of animals, indicating that the vaccine was
not effective in clearing P. gingivalis from the gum tissue.  However,
dental X rays and bone density measurements taken 30 and 36 weeks after the
inoculations showed that the nonvaccinated monkeys had lost twice as much
tooth-supporting bone as had the vaccinated animals. Although the vaccine
elicited relatively large amounts of antibody against P. gingivalis, the
antibody response did not appear to be long-lasting.  Antibody titers
peaked after the third injection (at week 6), decreasing by 50 percent by
week 12. The titer increased again following the fourth injection (at week
16), but dropped by more than half by week 36.

     In spite of the dissipating antibody response, vaccination protected
the monkeys against a challenge with the bacteria. In a test conducted at
week 36, Dr.  Page and his colleagues applied live P. gingivalis bacteria
directly to the gum lines of six monkeys-three vaccinated and three
nonvaccinated animals. Eight weeks later, the vaccinated animals appeared
to be completely resistant to this bacterial onslaught, while the control
animals showed rapid and dramatic bone loss.

     " It appears that immunization may in fact block bacterially induced
bone loss," says Dr. Page. "Over the next 5 years we're going to study why
the vaccine works, how it works, and whether we will be able to produce a
vaccine that effectively reduces the level of bacteria in the gum tissue."



------------------------------

Date: Wed, 15 Jun 94 06:49:26 MST
From: mednews (HICNet Medical News)
To: hicnews
Subject: An Unexpected Window on High Blood Pressure
Message-ID: <[e-mail]>

An Unexpected Window on High Blood Pressure
NCRR Reporter; May/June 1994

     Nobody realized it at the time, but when Gloria Brown checked into the
renal transplantation unit at the University of Alabama at Birmingham
(UAB) Medical Center, she was setting in motion a clinical study that
would involve nearly 100 members of her extended family. In the end her
case would help to uncover the origins of a rare inherited ailment,
trigger a spate of discoveries, and spur new lines of research related
to the causes of high blood pressure, which affects more than 60 million
Americans.
     At first glance Ms. Brown's case did not seem terribly unusual. Each
year UAB provides new kidneys to more than 250 patients, and Ms. Brown
was one of the many whose renal failure could not be fully explained.
But looking at her medical records, an astute postdoctoral fellow noted
that this patient also had a rare inherited disorder known as Liddle
syndrome, which leads to severe hypertension. In fact, more than three
decades ago, while under the care of Dr. Grant W. Liddle at Vanderbilt
University's General Clinical Research Center (GCRC), Ms. Brown was the
first person ever to be diagnosed with this syndrome.
     The fellow, Dr. Mauricio Botero-Velez, consulted with Dr. David G.
Warnock, professor of medicine and director of the division of nephrology
at UAB, and Dr. John J. Curtis, medical director of UAB's kidney
transplant program and principal investigator of the university's GCRC.
The researchers realized that they were presented with a rare
opportunity to probe the origins of high blood pressure. Liddle
syndrome, when undiagnosed or untreated, leads to soaring hypertension
and sometimes to premature death from stroke or heart failure. Five of
Ms. Brown's relatives had died in this way at an early age.
     When Dr. Liddle first evaluated Gloria Brown and 22 members of her
family back in the 1960's, he discovered that their ailment mimicked a
disorder known as primary aldosteronism. Liddle syndrome, in fact, is
sometimes called pseudoaldosteronism. Both conditions are marked by high
blood pressure that worsens dramatically when salt is consumed, but the
biological origins of these disorders are very different. Aldosteronism
results from overly vigorous adrenal glands that produce excess
aldosterone, the hormone that causes kidneys to retain sodium and water.
With Liddle syndrome aldosterone is barely detectable in the blood, yet
the kidneys behave as though they were constantly bathed in the hormone.
Because the kidneys retain sodium and water, blood volume expands and
blood pressure soars.
     Dr. Liddle speculated that the kidneys themselves, and not an
imbalance of the hormones that act on the kidneys, must be the culprit
behind Liddle syndrome. But over the next 30 years no one was able to
determine with certainty whether he was correct. By a stroke of
serendipity the Alabama researchers were able to put Dr. Liddle's
hypothesis to the test.
     "The patient was at UAB to get a new kidney, and we realized that the
operation would quite possibly reverse the manifestations of the
disease," says Dr. Warnock. And indeed that is what happened. Ms. Brown
received her new kidney without complication in November 1989. Once the
organ was in place and functioning, the clinical indicators of Liddle
syndrome--including severe hypertension and suppressed aldosterone
secretion--dissipated. "We were able to confirm Grant Liddle's
speculations from 30 years ago," says Dr. Curtis. "He believed that the
defect lies within the kidney itself, and with the kidney transplant it
became fairly obvious that he was right."
     Confirming Grant Liddle's hypothesis may at first seem esoteric, but
it will likely have important implications for understanding more common
forms of hypertension, says Dr. Curtis. Despite the prevalence of
hypertension, clinicians can identify its cause in fewer than 10 percent
of cases. The remaining 90 percent are categorized as "essential
hypertension." Dr. Curtis speculates that many cases of essential
hypertension are attributable to malfunctions in the kidneys themselves,
as in Liddle syndrome. "This rare disease may turn out to be not so rare
in terms of its underlying mechanisms. If Liddle syndrome helps us to
understand how the kidney tubules handle salt, it might help us to
advance knowledge about essential hypertension in general," says Dr.
Curtis.
     From a clinical standpoint, scrutinizing the microscopic tubules and
their salt-regulating activities deep within the kidneys can be
problematic. But UAB researchers believe Liddle syndrome has led them to
a simple cellular model for how the kidneys manage salt. Dr. Warnock and
Dr. James K. Bubien, assistant professor of medicine at UAB, discovered
that the white blood cells of Liddle syndrome patients have irregular
sodium channels that seem to be permanently open, allowing sodium to
continually pass into and out of the cells. This finding complements an
earlier study, conducted in the 1970's, which reported that sodium
movement was also exceptionally high in the red blood cells of Liddle
syndrome patients. Because similar types of sodium channels are found in
the kidney's tubules, the blood cells may serve as an accessible window
on sodium transport in the kidneys.
     Along another avenue of inquiry, UAB scientists hope to pinpoint the
gene that causes Liddle syndrome. The researchers have tracked down
nearly 100 of Gloria Brown's relatives--both living and dead, related by
blood or marriage--and produced a five-generation family tree. By far
the largest known kindred with Liddle syndrome, Ms. Brown's extended
family is an ideal target for genetic analysis, says Dr. Warnock. The
family tree confirms that Liddle syndrome is inherited in an autosomal
dominant fashion, which means that about half of the children of
affected parents inherit a predisposition to the disease. "This family
is so large--and with so many members affected or unaffected with Liddle
syndrome--that we are quite optimistic that we will be successful in
finding the gene," says Dr. Warnock. "If we are able to isolate, define,
and identify the gene, we will then know one of the major players that
regulates the renal absorption of salt." The scientists already have
ruled out several candidate genes such as those that produce the
aldosterone receptor and some components of the cellular sodium
channel.
     Gloria Brown's story has essentially come full circle in a GCRC
setting, notes Dr. Curtis. She was originally treated at Vanderbilt's
GCRC, which was founded in 1960 and is one of the oldest GCRC's in the
country. There she was diagnosed as having an atypical form of
hypertension. But now, at UAB's GCRC, her condition has been cured, and
studies of her and her family are opening up novel opportunities for
understanding more common causes of high blood pressure.
     "It's very interesting that she ended up at two different GCRC's at
two different times, and each time made a major contribution to our
understanding of hypertension in general," says Dr. Curtis. "The fact
that GCRC's have been in existence for a long time allowed us to follow
through on a study Grant Liddle began 30 years ago. This patient's story
illustrates the value of GCRC's and the in-depth, thoughtful workups
patients receive in these settings."

Additional Reading
1. Warnock DG, Bubien JK. Cellular physiology of Liddle's syndrome.
Hospital Practice, in press.
2. Botero-Velez M, Curtis JJ, Warnock DG. Brief report: Liddle's syndrome
revisited--A disorder of sodium reabsorption in the distal tubule. N
Engl J Med 330:178-81 1994.



------------------------------

Date: Wed, 15 Jun 94 06:51:06 MST
From: mednews (HICNet Medical News)
To: hicnews
Subject: Institute of Tropical Medicine Epidemiological Bulletin
Message-ID: <[e-mail]>

IPK - EPIDEMIOLOGICAL BULLETIN     Vol 4e / No.17
                                   Date: 04/30/94


Institute of Tropical Medicine Pedro Kouri
National Epidemiology Office
Ministry of Public Health
------------------------------------------------------------

Cuba. Cases and Cumulative of selected notifiable diseases.
Week ending 04/30/94.
------------------------------------------------------------
 DISEASES           IN THIS WEEK        CUMULATIVE
                    1992      1993      1992      1993
------------------------------------------------------------
TYPHOID FEVER       1         1         9         15
SHIGELLOSIS         1         11        85        66
AMEBIAN D.          7         4         1486      121
TUBERCULOSIS        18        18        231       278
HANSEN DISEASE      11        9         69        63
PERTUSSIS           *         *         4         *
SCARLET FEVER       10        9         160       128
MENINGOCOCCAL M.(1) *         *         26        22
MENINGOCCEMIES(1)   *         2         5         7
TETANUS             *         1         *         1
VIRAL M.            48        95        789       1372
BACTERIAL M.        9         15        366       426
VARICELLA           2099      1910      24743     21143
MEASLES             *         *         *         *
RUBELLA             *         *         *         *
VIRAL HEPATITIS     364       340       5752      5201
MUMPS               *         *         *         *
MALARIA             1         *         3         1
LEPTOSPIROSIS       19        19        158       304
SYPHILIS            166       226       3127      3668
GONORRHEA           393       566       6693      8277
ACUMINATA COND.     47        47        719       617
------------------------------------------------------------
 Source:  1993, MND (Written Report) EIG-IPK.
          1994, MND (Phone Report) EIG-IPK.
          (1) DIS
          * Means 0 reported case.

------------------------------------------------------------
     This bulletin was prepared with the 69% of provinces-days-
     information.

     The offered indexes are provisionals and were taken from
     the daily report of the Direct Information System (DIS)
     remitted by Provincial Centers of Hygiene and
     Epidemiology, from the weekly phone report of Mandatory
     Notifiable Diseases (MND) remitted by National Statistics
     Division of the Ministry of Public Health, and from the
     Reference Laboratories of the Institute of Tropical
     Medicine Pedro Kouri.
------------------------------------------------------------

     This is the weekly IPK-Epidemiological Bulletin emitted
     via Electronic Mail. The numbering plan agree with the
     IPK-Epidemiological Bulletin edited by Institute of
     Tropical Medicine Pedro Kouri and it is an abbreviated
     version.

     Lic. Andres M. Alonso [e-mail]



IPK - EPIDEMIOLOGICAL BULLETIN     Vol 4e / No.18
                                   Date: 05/07/94


Institute of Tropical Medicine Pedro Kouri
National Epidemiology Office
Ministry of Public Health
------------------------------------------------------------

Cuba. Cases and Cumulative of selected notifiable diseases.
Week ending 05/07/94.
------------------------------------------------------------
 DISEASES           IN THIS WEEK        CUMULATIVE
                    1993      1994      1993      1994
------------------------------------------------------------
TYPHOID FEVER       *         *         9         15
SHIGELLOSIS         1         *         86        66
AMEBIAN D.          7         *         1493      121
TUBERCULOSIS        14        15        245       293
HANSEN DISEASE      6         5         75        68
PERTUSSIS           *         *         4         *
SCARLET FEVER       7         4         167       132
MENINGOCOCCAL M.(1) 1         2         27        24
MENINGOCCEMIES(1)   *         1         5         8
TETANUS             *         *         *         1
VIRAL M.            30        148       819       1520
BACTERIAL M.        11        20        377       446
VARICELLA           1775      1509      26518     22652
MEASLES             *         *         *         *
RUBELLA             *         *         *         *
VIRAL HEPATITIS     260       321       6012      5522
MUMPS               *         *         *         *
MALARIA             *         *         3         1
LEPTOSPIROSIS       5         21        163       325
SYPHILIS            220       181       3347      3849
GONORRHEA           334       492       7027      8769
ACUMINATA COND.     43        29        762       646
------------------------------------------------------------
 Source:  1993, MND (Written Report) EIG-IPK. 1994,
MND (Phone Report) EIG-IPK.
          (1) DIS
          * Means 0 reported case.


Notified Outbreaks. Week 05/05/94 - 05/11/94.
------------------------------------------------------------
 DISEASES      OUTBREAKS      CASES     PROVINCES
------------------------------------------------------------
 F.T.D.        1              187       CAMAGUEY
------------------------------------------------------------
VIRAL HEP.     3              18        PROV. HABANA 1/6
                                        VILLA CLARA 1/4
                                        CIEGO DE AVILA 1/8
------------------------------------------------------------
 Source:  DIS.

------------------------------------------------------------
     This bulletin was prepared with the 68% of provinces-days-
     information.

     The offered indexes are provisionals and were taken from
     the daily report of the Direct Information System (DIS)
     remitted by Provincial Centers of Hygiene and
     Epidemiology, from the weekly phone report of Mandatory
     Notifiable Diseases (MND) remitted by National Statistics
     Division of the Ministry of Public Health, and from the
     Reference Laboratories of the Institute of Tropical
     Medicine Pedro Kouri.
------------------------------------------------------------

     This is the weekly IPK-Epidemiological Bulletin emitted
     via Electronic Mail. The numbering plan agree with the
     IPK-Epidemiological Bulletin edited by Institute of
     Tropical Medicine Pedro Kouri and it is an abbreviated
     version.

    Lic. Andres M. Alonso [e-mail]



------------------------------

End of HICNet Medical News Digest V07 Issue #26
***********************************************

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